Available online on 15.04.2025 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

Copyright  © 2025 The  Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

Open Access  Full Text Article                                                                                                                                                       Review Article

An Updated Perspective of Silk Fibroin-Nanoparticle as a Carrier for Controlled Drug Delivery

Tomal Chandro Roy ¹*, Md. Ekhlass Uddin ¹, Arpa Kar ²

¹ Department of Chemistry, Rajshahi University, Rajshahi, Bangladesh

² Department of Chemistry, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh

1. Introduction:

The drug delivery system (DDS) is designed for delivery of drugs in the target site through a controlled manner that leads to therapeutic efficacy. It consists of a carrier system in which the active drug is dissolved, dispersed, or encapsulated, or onto which the active ingredient is adsorbed or attached¹. Drug carrier materials play a significant role in the delivery of drugs. These carriers can be processed into different forms such as nanoparticles, microspheres, microcapsules, pills, emulsions, and so on. Among them, nanoparticles have attracted much attention for their ability to be used as an effective carrier in promoting drug efficacy². Nanoparticles as drug carriers were first developed around the 1970s by Birrenbach and Speiser³. Controlled drug delivery from implanted polymer-drug depots offers numerous advantages over traditional periodic systemic administration, including enhanced efficacy and cost-efficiency, reduction or elimination of unwanted side effects because of maintaining desirable therapeutic range without peaks and valleys which increases patient convenience and compliance ⁴. To meet these needs, many synthetic non-degradable materials or implantable pumps have been proposed, but biodegradable implants alleviate the need for surgical removal of the material after the end of therapy. Naturally derived biodegradable materials can offer superior biocompatibility compared to synthetic degradable materials⁵. Nanostructured materials are synthesized by either "bottom-up" or "top-down" processes. The bottom-up approach starts with atoms, ions, or molecules as “building blocks" and assembles nano-scale clusters or bulk material from them. The "top-down" methods for processing of nanostructured materials involve starting with a bulk solid and obtaining a nanostructure by structural decomposition^6,7. However, naturally derived materials frequently lack the necessary control of material properties that needed for long-term sustained-release applications. Because of superior encapsulation, controlled drug release, and high biocompatibility, biodegradable polymer nanoparticles have been widely employed as drug delivery systems⁸. A variety of polymeric materials have been employed as a drug delivery matrix. These materials include natural polymers like polysaccharides which include cellulose, chitosan, hyaluronic acid, alginate, dextran, starch, and proteins which include collagen, gelatin, elastin, albumin, and silk fibroin (SF), as well as synthetic biodegradable polymers like poly (lactic acid) (PLA), poly (ε-caprolactone) (PCL), and poly(glycolic acid) (PGA), poly(lactide-co-glycolide) PLGA ^9,10. Silk fibroin may be made into a variety of forms, including fibers, films, 3D scaffolds, and gels, for medication delivery and regenerative engineering research¹¹. Generally speaking, amorphous flexible chains strengthened by strong, stiff crystals are what make silkworm cocoons and spider dragline silks semi-crystalline materials. Particle dispersions in a fluid or gel phase are used in many pharmaceutical and medical technologies. Examples include custom coatings, sustained release, and drug delivery systems¹².Silk proteins' capacity to be processed in water, biocompatibility, and biodegradability make them a suitable substrate for drug delivery. A basic aqueous technique is required for the manufacture of silk fibroin particles¹³.During processing, the majority of silks take on a variety of secondary structures, such as insoluble spun fibers or soluble protein in the glands. Because of their distinct functions, protein-based nanoparticle drug delivery methods have gained attention. Protein-based carriers have outstanding biocompatibility, non-antigenic, and biodegradability¹⁴. Furthermore, proteins can a biological reaction in cells and display a variety of functional groups. In particular, covalent drug and ligand attachment can alter the surface of protein nanoparticles to improve therapeutic efficacy^15,16.

2. Silk-fibroin Features:

Silk fibroin, often known as Bombyx mori, is a naturally occurring protein derived from silkworm cocoons. Its predominant amino acid composition consists of glycine, alanine, and serine. It stands out due to its fibrous structure and elevated levels of hydrophobic amino acids. Bombyx mori silk fibroin is a stable protein possessing good mechanical properties, such as high elasticity and tensile strength¹⁷. It is resilient to a broad variety of environmental factors. Silk fibroin from Bombyx mori can be made by dissolving the cocoons in aqueous alkali solutions and spinning the resulting solution to form fibers. After that, several products, including hydrogels, films, and fibers, can be made from the silk fibroin fibers by treating them^18,19. Silk fibroin from Bombyx mori has been extensively studied for its possible biological applications, particularly in the field of drug administration. Because of its ability to prevent encapsulated medications from degrading and its biocompatibility and biodegradability, it is a desirable material for drug delivery. Silk fibroin from Bombyx mori can be used to make silk fibroin nanoparticles (SFNs), which can encapsulate a variety of medications, proteins, and other biomolecules and can be tailored in terms of size, shape, and release kinetics²⁰. Additionally, research has been done on the potential applications of Bombyx mori silk fibroin, which include tissue engineering, wound healing, and cell growth scaffolding²¹. Because it is biocompatible, biodegradable, and non-toxic, silkworm (Bombyx mori) silk fibroins, a naturally occurring protein derived from the cocoons of silkworms, have drawn a lot of attention as possible drug delivery vehicles. Its exceptional mechanical properties, which make it suitable for a range of biomedical applications, and its ability to stop encapsulated drugs from deteriorating, make it an ideal material for drug delivery²². Because it can be functionalized with other biomolecules to enhance its targeting and release kinetics, it is adaptable³². A protein-based biomolecule with good biocompatibility, biodegradability, and minimal immunogenicity is called silk fibroin (SF). The development of SF-based nanoparticles for drug administration has drawn a lot of interest because of their versatile drug-binding capability, controlled release characteristics, and easy production. The therapeutic efficacy of pharmaceuticals contained in qualified or recombinant SF-based nanoparticles can be enhanced by programming changes to the particle size, chemical structure (Figure 1), and characteristics. As a result, they can be utilized to deliver gene medications, protein and growth factor drugs, and small molecule drugs (such as anti-cancer drugs)^24,25,26.

The main components of the naturally occurring protein known as silk fibroin are serine, glycine, and alanine. The two primary domain types that comprise this fibrous protein are the crystalline domains, which are composed of densely packed beta-sheet structures, and the amorphous domains²⁰, which are composed of random coil patterns. The chemical composition of silk fibroin has a large number of hydrophobic amino acids, such as alanine and glycine, and a small number of charged and polar amino acids, such as tyrosine and histidine. Silk fibroin have self-assemble structures in water because of its hydrophobic qualities²¹. Silk fibroin is a highly stable protein that can withstand a wide range of environmental conditions, such as high temperatures, pH changes, and contact with organic solvents²⁸. The presence of intramolecular and intermolecular hydrogen bonds, which support the structural maintenance of the protein, is responsible for its stability²⁹. Silk fibroin's exceptional tensile strength makes it an ideal material for biomedical applications, such as wound dressings and surgical sutures. Its exceptional mechanical properties enable it to be utilized in the production of numerous materials, such as films, fibers, and hydrogels ³⁰.

Figure 1: Primary structure of silk fibroin.

Overall, due to its chemical makeup and physical characteristics, silk fibroin is a desirable material for the utilization of various biomedical applications. It is especially useful as a drug delivery vehicle due to its biocompatibility, biodegradability, and ability to stop the encapsulation of pharmaceuticals from degrading³¹.

Fibroin, the main component of silkworm silk fiber, and spider silk fiber's equivalent, saproin, are two significant families of silk proteins. The two protein chains that make up the B. mori silk fibroin are the heavy chain (H-fibroin), which has a molecular weight of around 350 kDa, and the light chain (L-fibroin, Mw ~ 26 kDa), which is covalently bonded at the carboxy-terminus of the two subunits by a disulfide bond^33,34,35(Figure 2a& 2b).

Figure 2: (a) A highly repetitive heavy chain and a non-repetitive light chain joined by covalent bonds make up silkworm fibrin. (b) Non-repetitive amino-(NRN) and carboxy-terminal (NRC) domains encircle the primary repetitive core domain of spider silk spidroins³⁶.

Like silk fibroin from Bombyx mori, the main constituents of these proteins are serine, glycine, and alanine³⁷. However, spider silk fibroins are not the same as silkworm silk fibroins in terms of composition and structure. Spider silk fibroins differ from silkworm silk fibroins in that they have a reduced amount of hydrophobic amino acids and a higher degree of secondary structure, such as beta-sheet and alpha-helix. As a result, spider silk fibroins have exceptional mechanical properties, such as high tensile strength, high extensibility, and high toughness³⁸. Spider silk fibroins have been thoroughly studied for their possible applications in biomedicine, particularly as a drug delivery system. Spider silk fibroins have strong biocompatibility and biodegradability, making them an effective material for biomedical applications³⁹. Additionally, many biomolecules can be functionalized onto spider silk fibroins to enhance their targeting and release kinetics. Spider silk fibroins are highly versatile and can be employed in many different activities, including wound healing, tissue engineering, and cell growth scaffolding. Because it is non-toxic, biocompatible, and biodegradable, spider silk fibroins—a naturally occurring protein derived from spider silk—have been thoroughly studied as possible drug delivery vehicles⁴⁰. Its remarkable mechanical properties make it suitable for various biomedical applications; additionally, its versatility stems from its capacity to be functionalized with various biomolecules to enhance its release kinetics and targeting abilities^41. Furthermore, the presence of various chemical groups in the structure of SF, such as amines, phenol, alcohol, thiol, and carboxyl, promotes the interaction of SF with particular cell types' antibodies and biomolecules. It is feasible to include different medications inside or on the surface of SF fibers by turning on the various SF functional groups. SF is thus shown as a potent drug carrier with a variety of biomedical applications. (Figure 3)³⁷.

Figure 3: Different types of modification strategies for changing the surface properties of SF⁴³.

Silk fibroin (SF) is an attractive material for use in many applications, including the delivery of medications, due to its many physical properties. The following are some of the fundamental physical traits of SF: High elasticity, high toughness, and high tensile strength are some of SF's excellent mechanical qualities. Owing to these properties, SF finds utility in numerous fields such as tissue engineering and wound healing³⁸.

• Biocompatibility: Being biocompatible means that SF does not trigger an immune response when it comes into contact with living tissue. For these reasons, SF is a sought-after material for biomedical applications⁴⁵.
• Biodegradability: SF can be broken down by the body's enzymes and other systems because it is biodegradable. SF is a useful option in applications where the material must be removed after a specific period⁴⁶. SF is attracted to water due to a characteristic known as hydrophobicity. This property makes SF a promising material for use in hydrogels and other water-based systems⁴⁷.
• Hydrophobicity: Numerous hydrophobic amino acids are present in SF, and they can be changed to suit the requirements of the application. Two properties of SF that make it suitable for usage in circumstances where the material will be exposed to extremes of heat or cold are thermal stability and a wide temperature range⁴⁸.
• Transparency: SF films and fibers can be employed in optical applications since they are transparent⁴⁹. Because SF is porous, the rate at which drugs and other substances are released from SF-based drug delivery systems can be controlled by altering its structure. These qualities make SF an attractive material for many biomedical applications, such as wound healing, tissue engineering, and medication administration^50,51.

3. Preparation Methods of Silk Fibroin-Based Nanoparticles:

Many methods, such as salting out, mechanical comminution, desolvation, electrospraying, and supercritical fluid technologies, can be used to create SF-based nanoparticles.

• Salting out:

Salting out is a widely used technique in chemistry and molecular biology for the purification and precipitation of proteins and nucleic acids. This process involves the addition of a high salt concentration to a solution containing a biomolecule of interest. He increased ionic strength disrupts the solvation shell around the biomolecule, thereby promoting aggregation and precipitation. Typically, ammonium sulfate is the salt of choice because of its high solubility and its ability to effectively precipitate a wide range of proteins ⁴⁶. This process is usually carried out in a stepwise manner, gradually increasing the salt concentration to selectively precipitate different proteins based on their solubility properties. This method not only aids in the concentration of proteins but can also be used to enhance their purity by removing contaminants that remain soluble under similar salt conditions ⁴⁷. For optimal results, various parameters such as pH, temperature, and specific salt concentration must be carefully controlled. The resulting precipitate was collected via centrifugation, washed, and suspended in a suitable buffer for further analysis or purification ⁴⁸. These are a few benefits and drawbacks of the salting-out technique used to create silk fibroin nanoparticles. It should be mentioned, nevertheless, that the salting-out technique is still a practical and popular way to create silk fibroin nanoparticles.

Top of Form

One technique for separating and purifying proteins from natural sources, such as silk fibroin (SF), is the salting-out process (Figure 4). It is predicated on the theory that the increased electrostatic attraction between the protein molecules causes the proteins in a solution of proteins to "precipitate," or separate from the solution when salt is added. The target protein is dissolved in water together with any other possible contaminants or impurities. The mixture is salted, frequently using a salt with a high molecular weight, such as ammonium sulfate. As the concentration of salt increases, the proteins begin to precipitate out of the solution. Before the precipitate is recovered by centrifugation or filtering, the protein is rinsed and dried to remove any remaining salt.

Figure 4. Diagrammatic representation of the salting out process used to create SF nanoparticles salting-out ⁶³.

After being purified, the protein might be used for several things. The salting out method is widely used to extract proteins, such as silk fibroin, from natural sources since it is inexpensive and simple to use. Some of its disadvantages include the potential for denaturing the protein and the need to eliminate salt before utilizing the protein in specific applications. It is significant to highlight that the salting out methodology has recently advanced to overcome some of the limitations of previous methods, such as the requirement of low-molecular-weight salts and the requirement to purify SF using aqueous two-phase systems (ATPS). Some experts claim that the salting out method is a simple and affordable way to purify proteins. Additionally, they emphasize that it is a widely used approach in both industry and research and has been well-established for several years⁶⁴. Some, however, highlight the disadvantages of the salting out technique. For example, the protein may be denatured by the high salt concentrations used in the procedure, which could affect the protein's structure and functional properties. Some experts assert that the salting-out method can be improved by using salts with low molecular weight or by combining it with other methods of purification such as size-exclusion chromatography⁶⁵. While the salting out approach is widely used to purify proteins, scientists have differing opinions about its effectiveness and limitations. It is a simple, low-cost process, but its effectiveness can be enhanced by using low-molecular-weight salts or by combining them with other purification methods.

• Desolvation:

Desolvation is a crucial method used to purify and concentrate biomolecules, especially proteins and nucleic acids. This technique involves stripping water molecules from the solvation layer surrounding a biomolecule, which leads to precipitation or aggregation. By diminishing the hydration shell, desolvation strengthens the interactions between biomolecules, aiding in their separation from impurities. The procedure typically starts by altering solution conditions, such as ionic strength, pH, or temperature, to induce desolvation. Commonly used agents in this process include organic solvents (like acetone or ethanol) and salts that interfere with solvation dynamics ⁶². In the case of proteins, desolvation can trigger conformational changes, often resulting in precipitation, which is then harvested through centrifugation or filtration. One of the key advantages of desolvation is its ability to selectively isolate specific proteins based on their distinct solubility characteristics. It can also enhance the yield and purity of the target biomolecule by effectively eliminating soluble contaminants ^63,64. This approach is extensively utilized in protein crystallization, where precise management of desolvation is essential for producing high-quality crystals. These are a few benefits and drawbacks of the desolvation technique used to create silk fibroin nanoparticles (Figure 5).

Figure 5: Schematic diagram of the desolvation method for preparing silk fibroin (SF) nanoparticles⁷⁴.

While desolvation offers certain advantages in the production of silk fibroin nanoparticles for controlled drug delivery, some disadvantages need to be considered. The process of desolvation involves removing solvent molecules from a substance, typically a protein or other biomolecule. It is a crucial phase in the purification and separation of the molecule. Industry experts generally view the desolvation method favorably. They stress how effective it is at eliminating solvent molecules and how it may be used in conjunction with other purification methods, such as chromatography, to create extremely pure protein or biomolecule samples. Because desolvation procedures maintain the chemical and physical properties of the protein or biomolecule, they are also often preferred over alternatives like precipitation and lyophilization⁷⁵. Experts also note that desolvation can be a time-consuming procedure and that the necessary equipment can be expensive. Additionally, certain proteins or biomolecules may be more difficult to dissolve than others based on their solubility qualities⁷⁶. Recent research has shown that the desolvation process can be improved by utilizing state-of-the-art technology, such as supercritical fluid technology, which provides a gentle, efficient, and effective way of desolvation and drying process (Figure 6). To summarize, experts think that desolvation is a good method for getting rid of solvent molecules from proteins or biomolecules, and it can be used with other methods of purification to get extremely pure samples⁷⁷.

Figure 6: Schematic formation mechanism of the hierarchical assembly from molecular silk fibroin to microfibers ⁷⁸.

They also mention that some proteins or biomolecules may be more difficult to dissolve than others and that desolvation can take a lengthy period. Recent research has shown that the procedure can be enhanced by applying state-of-the-art technologies, like supercritical fluid technology.

• Electrospraying:

Electrospraying is an innovative technique utilized for the production of fine aerosol droplets from liquid solutions and is frequently employed in the fields of nanotechnology, material science, and pharmaceuticals. This process utilizes an electric field to induce the formation of a spray from a charged liquid, which is subsequently directed towards the target substrate or collector. The electrospraying process commences with the application of a high voltage to a liquid feed, which typically contains polymers, biomolecules, or nanoparticles ⁷⁴. The electric field causes the liquid to form a Taylor cone at the tip of the nozzle, from which a fine jet emerges. As the jet traverses through air, it undergoes solvent evaporation and fragmentation, resulting in the generation of ultrafine particles or fibers. One of the significant advantages of electrospraying is its capacity to produce uniform and controllable particle sizes, which is critical for applications such as drug delivery, where precise dosage and release profiles are desired ⁷⁵. The parameters that influence the electrospraying process include the solution viscosity, concentration, applied voltage, and distance between the nozzle and collector ⁵². Electrospraying is particularly valuable for encapsulating active compounds and for enhancing their stability and bioavailability. This methodology has gained prominence for the production of nanofibers, nanoparticles, and microcapsules for various biomedical and industrial applications. The electro-spraying approach (Figure 7) for the manufacture of silk fibroin nanoparticles has the following benefits and drawbacks.

Figure 7: Schematic illustration of the SF nanoparticle preparation process using electrospraying⁸⁷.

Overall, electro-spaying is a promising method for producing silk fibroin nanoparticles for medication delivery; however, careful consideration of the advantages and disadvantages is necessary to ensure optimal performance and results.

Electrospraying is a technique used to create microscopic droplets or particles of a liquid by subjecting it to a high electric voltage, which causes the liquid to break down into tiny droplets or particles. It is used in several fields, such as material science, biotechnology, and medicine delivery. The majority of expert opinions regarding electrospraying are positive. They emphasize that it is a versatile procedure that can be used to produce particles with a variety of sizes and shapes as well as ones composed of materials that are difficult to produce using other methods. Furthermore, monodispersity and considerable surface functionality can be produced via electrospraying⁸⁸. Experts also note that the process of electrospraying may be difficult and that the necessary equipment can be expensive. Additionally, certain materials may be more difficult to electrospray than others based on their unique properties. Recent research indicates that electrospraying has been applied to produce drug delivery systems, protein particles, and other biomolecules. This method can also be used to generate particles made of metal, ceramic, or polymer. According to experts, electrospraying is a versatile technology that can be used to produce particles with a wide range of sizes and forms as well as ones composed of materials that are difficult to produce using other methods. They do, however, also note that the electrospraying method can be challenging and that the necessary supplies could be expensive. The method's versatility in manufacturing particles for many applications has been exhibited by recent investigations.

• Mechanical Comminution:

Mechanical comminution is a widely utilized technique for size reduction of solid materials and is primarily employed in the fields of materials science, mineral processing, and pharmaceuticals. This process involves the application of mechanical forces to break down larger particles into finer ones, thereby increasing the surface area and enhancing the reactivity or bioavailability of materials ⁸². The mechanical comminution process typically encompasses several methods such as crushing, grinding, milling, and pulverization. Various types of equipment can be employed depending on the desired particle size and material characteristics, including ball mills, hammer mills, jet mills, and attrition mills ²¹. Each method operates on distinct principles, with some relying on impact forces and others utilizing shear or compression forces. Key parameters influencing the efficacy of mechanical comminution include the type of material being processed, the size and morphology of the feed particles, and operating conditions such as speed, duration, and moisture content. The optimization of these parameters is essential for achieving the desired particle size distribution and minimizing energy consumption. Mechanical comminution is particularly advantageous in industries where precise particle size is crucial, such as the formulation of pharmaceuticals, where it can enhance the dissolution rates of active ingredients. Additionally, it plays a vital role in the recycling of materials, facilitating the recovery of valuable components from waste products ⁸³. These are a few benefits and drawbacks of the mechanical comminution technique used to create silk fibroin nanoparticles.

Overall, there are certain advantages to mechanical comminution, such as scalability and control over particle size, but there are also disadvantages, such as the requirement for specialized equipment and the potential for deterioration of silk fibroin. As with any approach, the selection of mechanical comminution will depend on the particular needs of the application. Mechanical comminution is one method of reducing materials to very small particles⁹⁷. It is a widely used technology in a variety of industries, such as mining, food processing, and pharmaceuticals. Reviews of the mechanical comminution method by industry specialists have generally been positive. They stress how simple it is to scale up for large-scale operations and how efficient and fast it can be used to reduce particle size (Figure 8). Furthermore, mechanical comminution processes are usually preferred over alternatives like chemical or heat treatments since they do not alter the chemical or physical characteristics of the material being comminuted⁹⁸. Experts also note that mechanical comminution procedures can require expensive and energy-intensive equipment. Additionally, some materials may be more difficult to comminute than others based on their mechanical properties⁹⁹. The mechanical comminution process can be enhanced with the use of high-pressure homogenization (HPH) and ultrasonic technologies, which will make the process more precise, effective, and gentle¹⁰⁰.

Figure 8: Diagram illustrating the nucleation and self-assembly of silica into nanocomposites¹⁰¹.

However, mechanical comminution is a simple and efficient method of reducing particle size, but they also point out that it can be energy-intensive and that comminution may be more difficult for some materials than for others. Recent research has shown that the process can be improved by utilizing state-of-the-art tools like ultrasonic and high-pressure homogenization (HPH).

4. Silk fibroin biomaterials for controlled-release medication delivery:

A natural protein-based biomaterial called silk fibroin has been extensively explored for its possible application in the distribution of controlled-release medications. The use of silk fibroin biomaterials for controlled-release medication administration is generally viewed favorably by experts, and several researchers have highlighted its benefits. Silk fibroin is easily processed into a range of forms, including hydrogels, microparticles, and nanoparticles, which can be used to encapsulate pharmaceuticals. It has been demonstrated to be both biocompatible and biodegradable. Furthermore, research indicates that a broad spectrum of medications, including important macromolecules like proteins and nucleic acids as well as tiny compounds, may be present in silk fibroin¹⁰². Furthermore, silk fibroin has been shown to have low toxicity and immune-stimulating properties, which makes it a great choice for controlled-release drug administration¹⁰³. There are still issues to be resolved before silk fibroin is widely used as a drug delivery system animal. One of the main issues is enhancing the stability of silk fibroin-based delivery methods to prevent drug leakage. Controlling the rate at which medications are released from silk fibroin-based delivery systems is another problem that has to be resolved¹⁰⁴. All things considered, the fabrication of silk fibroin biomaterials (Figure 9) could be used to administer controlled-release medications, however further research is needed to address the problems that need to be fixed.

Figure 9: Production of Particles of Silk ¹⁰⁵.

5. The Applications of Nanoparticles Based on Silk Fibroin for Drug Delivery:

Silk fibroin-based nanoparticles have been studied as a possible drug delivery strategy because of their biocompatibility, biodegradability, and low immunogenicity. Silk fibroin is a naturally occurring protein that can be easily extracted from silkworm cocoons and processed into nanoparticles using methods like solvent evaporation, electrospraying, and electrospinning. There are several scenarios in which drug delivery via silk fibroin-based nanoparticles could be employed.

• Cancer treatment: Due to their capacity to selectively target tumor cells and release the medicine under controlled circumstances, silk fibroin-based nanoparticles have been studied as a possible anticancer drug delivery system.
• Gene therapy: Silk fibroin-based nanoparticles have been shown to carry plasmid DNA, which can be used to introduce genetic material into cells.
• Vaccines: Silk fibroin-based nanoparticles have been studied as possible vaccine carriers because they can strengthen the immune response to the vaccination.
• Ocular drug delivery: Due to its ability to both reduce the number of doses required and enhance drug retention in the eye, silk fibroin-based nanoparticles have been studied as a potential drug delivery technology.
• Dermal drug delivery: Since silk fibroin-based nanoparticles may improve the drug's skin penetration and reduce the number of doses required, they have been studied as a possible carrier for dermal pharmaceuticals.
• Biomedical imaging: Silk fibroin-based nanoparticles are used as a contrast agent in computed tomography (CT) and magnetic resonance imaging (MRI) procedures.

While silk fibroin-based nanoparticles have great potential as drug-delivery vehicles (Table 1), further research is needed to fully understand their properties and optimize their use in a range of applications.

Table 1: Model medications contained in nanoparticles of silk fibroin ¹⁰⁶.

6. Expert Opinions:

Various reviews and research papers provide expert opinions regarding the use of silk fibroin-based nanoparticles for drug delivery. In a paper, the authors assessed the potential of silk fibroin-based nanoparticles as a drug delivery vehicle and highlighted the advantages of using them, such as their controlled drug release, biocompatibility, and biodegradability. Additionally, they discussed the challenges that must be overcome for silk fibroin-based nanoparticles to realize their full potential^107,108.The authors of the review study discussed the application of silk fibroin-based nanoparticles for cancer therapy. They discussed the advantages of using silk fibroin-based nanoparticles for targeted drug administration and assessed the current status of research in this area¹⁰⁹. An article discussed the usage of silk fibroin-based nanoparticles for the delivery of ophthalmic medications. They highlighted the advantages of using silk fibroin nanoparticles for the delivery of ocular medications, such as their regulated release capabilities and biocompatibility. They also highlighted the challenges that must be solved for silk fibroin-based nanoparticles to fulfill their full potential in the delivery of ocular medications^110,111.An article mentioned using silk fibroin-based nanoparticles for gene therapy. The advantages of using silk fibroin-based nanoparticles for gene transfer were highlighted, including their controlled gene release properties, biocompatibility, and biodegradability^. They also discussed the challenges that must be solved for silk fibroin-based gene therapy nanoparticles to realize their full potential¹¹².

An article described the use of silk fibroin-based nanoparticles for protein delivery. They highlighted the advantages of using silk fibroin-based nanoparticles for protein delivery, including their regulated protein release capabilities, biocompatibility, and biodegradability. They also discussed the challenges that must be overcome for silk fibroin-based nanoparticles to fulfill their full promise in protein delivery^113,114.An article described the usage of silk fibroin-based nanoparticles for the transport of small compounds. They highlighted the advantages of using silk fibroin-based nanoparticles for the transport of small compounds, such as their controlled release properties, biocompatibility, and biodegradability. They also discussed the challenges that must be solved for silk fibroin-based nanoparticles to fulfill their full potential in the delivery of tiny molecules of therapy¹¹⁵.An article mentioned using silk fibroin-based nanoparticles as a cancer treatment. The advantages of silk fibroin-based nanoparticles for cancer therapy were highlighted, including their regulated drug release, biocompatibility, and biodegradability ^116,117. They also discussed the challenges that must be solved for silk fibroin-based nanoparticles to be fully utilized in cancer treatment¹¹⁸.A paper described the use of silk fibroin-based nanoparticles for gene editing. The advantages of using silk fibroin nanoparticles for gene editing were highlighted, including their capacity for regulated drug release, biocompatibility, and biodegradability. They also discussed the challenges that must be solved for silk fibroin-based gene editing nanoparticles to realize their full potential¹¹⁹.An article described the use of silk fibroin-based nanoparticles for targeted medication delivery. The advantages of using silk fibroin nanoparticles for targeted drug delivery were highlighted, including their ability to encapsulate a range of medications and their biocompatibility and biodegradability. They also discussed the challenges that must be solved for silk fibroin-based nanoparticles to fulfill their full potential in the targeted drug delivery industry¹²⁰.An article mentioned using silk fibroin-based nanoparticles to heal wounds. They highlighted the advantages of using silk fibroin-based nanoparticles for wound healing, such as their ability to deliver drugs with controlled release and biocompatibility^121,122. They also discussed the challenges that must be solved for silk fibroin-based nanoparticles to heal wounds to the fullest extent possible^123,124. An article examined the application of silk fibroin-based nanoparticles for skin delivery. They highlighted the advantages of using silk fibroin-based nanoparticles, such as their ability to stop drug degradation and their biocompatibility and biodegradability^125,98, for the transportation of medications through the skin. Additionally, they discussed the challenges that must be solved for silk fibroin-based nanoparticles intended for skin distribution to realize their full potential¹²⁷.These are just a few instances of current expert opinions; there are many more publications on the use of silk fibroin-based nanoparticles for medication administration and other therapeutic applications. Like with any new technology, more research is necessary to fully understand its features and make the most of it in a variety of applications.

7. Conclusions:

The emerging ideas may be included in this investigation that explore the use of silk fibroin-based nanoparticles for medication delivery: due to their biocompatibility, biodegradability, and capacity to encapsulate a variety of medicines, silk fibroin-based nanoparticles offer promise as a vehicle for regulated drug delivery. Research on targeted medication delivery via silk fibroin-based nanoparticles is ongoing and has the potential to increase treatment efficacy and lessen negative effects. The current difficulties in creating silk fibroin-based nanoparticles for drug delivery include heightening their stability, managing drug release, and enhancing targeting. To fully grasp the promise of silk fibroin-based nanoparticles for medication administration and to address the issues that must be resolved, more study is required. Future work on this project will focus on realizing the full potential of silk fibroin-based nanoparticles, and the knowledge gained could be useful to the development of cutting-edge controlled drug delivery systems.

Conflict of Interest: The authors declare no potential conflict of interest with respect to the contents, authorship, and/or publication of this article.

Author Contributions: All authors have equal contribution in the preparation of manuscript and compilation.

Source of Support: Nil

Funding: The authors declared that this study has received no financial support.

Informed Consent Statement: Not applicable.

Data Availability Statement: The data supporting in this paper are available in the cited references.

Ethical approval: This study does not involve experiments on animals or human subjects.

References:

1. Wang S, Xu T, Yang Y, Shao Z. Colloidal Stability of Silk Fibroin Nanoparticles Coated with Cationic Polymer for Effective Drug Delivery. ACS Appl Mater Interfaces. Published online 2015. https://doi.org/10.1021/acsami.5b05335 PMid:26331584
2. Rockwood DN, Preda RC, Yücel T, Wang X, Lovett ML, Kaplan DL. Materials fabrication from Bombyx mori silk fibroin. Nat Protoc. 2011;6(10):1612-1631. https://doi.org/10.1038/nprot.2011.379 PMid:21959241 PMCid:PMC3808976
3. Xu Z, Shi L, Yang M, Zhu L. Preparation and biomedical applications of silk fibroin-nanoparticles composites with enhanced properties - A review. Mater Sci Eng C. Published online 2019. https://doi.org/10.1016/j.msec.2018.11.010 PMid:30573254
4. Matthew SAL, Totten JD, Phuagkhaopong S, et al. Silk Nanoparticle Manufacture in Semi-Batch Format. ACS Biomater Sci Eng. Published online 2020. https://doi.org/10.1021/acsbiomaterials.0c01028 PMid:33320640
5. Lee OJ, Kim JH, Moon BM, et al. Fabrication and characterization of hydrocolloid dressing with silk fibroin nanoparticles for wound healing. Tissue Eng Regen Med. Published online 2016. https://doi.org/10.1007/s13770-016-9058-5 PMid:30603402 PMCid:PMC6170831
6. Hasanzadeh S, Farokhi M, Habibi M, et al. Silk Fibroin Nanoadjuvant as a Promising Vaccine Carrier to Deliver the FimH-IutA Antigen for Urinary Tract Infection. ACS Biomater Sci Eng. Published online 2020. https://doi.org/10.1021/acsbiomaterials.0c00736 PMid:33455198
7. Wang Q, Han G, Yan S, Zhang Q. 3D printing of silk fibroin for biomedical applications. Materials (Basel). Published online 2019. https://doi.org/10.3390/ma12030504 PMid:30736388 PMCid:PMC6384667
8. Roy TC. Journal of Drug Delivery and Therapeutics Silk Fibroin Hydrogel - Assisted Controlled Release of Antifungal Drug Ketoconazole. 2023;13(3):125-130. https://doi.org/10.22270/jddt.v13i3.5775
9. Bruder V, Ludwig T, Opitz S, Christoffels R, Fischer T, Maleki H. Hierarchical Assembly of Surface Modified Silk Fibroin Biomass into Micro-, and Milli-Metric Hybrid Aerogels with Core-Shell, Janus, and Composite Configurations for Rapid Removal of Water Pollutants. Adv Mater Interfaces. Published online 2021. https://doi.org/10.1002/admi.202001892
10. Haque Ansary R, Roy T, Asraf A, Easmin S. Preparation, Characterization and Antifungal Activity Studies of AgNPs Loaded Silk Fibroin Hydrogels. Am J Nano Res Appl. 2020;8(2):28. https://doi.org/10.11648/j.nano.20200802.13
11. Feng Y, Lin J, Niu L, et al. High molecular weight silk fibroin prepared by papain degumming. Polymers (Basel). Published online 2020. https://doi.org/10.3390/polym12092105 PMid:32947834 PMCid:PMC7570354
12. Roy T, Ansary RH. International Journal for Asian Contemporary Research ( IJACR ) Fabrication , Characterization and Antifungal Activity Studies of Silk Fibroin Hydrogel as a Potential Controlled Release of Fluconazole. 2021;1(I):31-38.
13. Lee MS, Hung CS, Phillips DA, Buck CC, Gupta MK, Lux MW. Silk fibroin as an additive for cell-free protein synthesis. Synth Syst Biotechnol. Published online 2020. https://doi.org/10.1016/j.synbio.2020.06.004 PMid:32637668 PMCid:PMC7320238
14. Jiang Y, Xu M, Yadavalli VK. Silk fibroin-sheathed conducting polymer wires as organic connectors for biosensors. Biosensors. Published online 2019. https://doi.org/10.3390/bios9030103 PMid:31466277 PMCid:PMC6784353
15. Zhang YQ, Shen W De, Xiang RL, Zhuge LJ, Gao WJ, Wang WB. Formation of silk fibroin nanoparticles in water-miscible organic solvent and their characterization. J Nanoparticle Res. 2007;9(5):885-900. https://doi.org/10.1007/s11051-006-9162-x
16. Wen DL, Sun DH, Huang P, et al. Recent progress in silk fibroin-based flexible electronics. Microsystems Nanoeng. Published online 2021. https://doi.org/10.1038/s41378-021-00261-2 PMid:34567749 PMCid:PMC8433308
17. Crivelli B, Bari E, Perteghella S, et al. Silk fibroin nanoparticles for celecoxib and curcumin delivery: ROS-scavenging and anti-inflammatory activities in an in vitro model of osteoarthritis. Eur J Pharm Biopharm. Published online 2019. https://doi.org/10.1016/j.ejpb.2019.02.008 PMid:30772432
18. De Moraes MA, Mahl CRA, Silva MF, Beppu MM. Formation of silk fibroin hydrogel and evaluation of its drug release profile. J Appl Polym Sci. 2015;132(15):1-6. https://doi.org/10.1002/app.41802
19. Calamak S, Aksoy EA, Ertas N, Erdogdu C, Sagiroglu M, Ulubayram K. Ag/silk fibroin nanofibers: Effect of fibroin morphology on Ag+ release and antibacterial activity. Eur Polym J. Published online 2015. https://doi.org/10.1016/j.eurpolymj.2015.03.068
20. Ansary RH, Rahman MM, Awang MB, Katas H, Hadi H, Doolaanea AA. Preparation, characterization, and in vitro release studies of insulin-loaded double-walled poly(lactide-co-glycolide) microspheres. Drug Deliv Transl Res. Published online 2016. https://doi.org/10.1007/s13346-016-0278-y PMid:26817478
21. Koh LD, Cheng Y, Teng CP, et al. Structures, mechanical properties and applications of silk fibroin materials. Prog Polym Sci. Published online 2015. https://doi.org/10.1016/j.progpolymsci.2015.02.001
22. Feng K, Li X, Bai Y, Zhang D, Tian L. Mechanisms of cancer cell death induction by triptolide: A comprehensive overview. Heliyon. 2024;10(2):e24335. https://doi.org/10.1016/j.heliyon.2024.e24335 PMid:38293343 PMCid:PMC10826740
23. Zheng D, Chen T, Han L, et al. Synergetic integrations of bone marrow stem cells and transforming growth factor-β1 loaded chitosan nanoparticles blended silk fibroin injectable hydrogel to enhance repair and regeneration potential in articular cartilage tissue. Int Wound J. Published online 2022. https://doi.org/10.1111/iwj.13699 PMid:35266304 PMCid:PMC9284642
24. Cheng G, Davoudi Z, Xing X, et al. Advanced Silk Fibroin Biomaterials for Cartilage Regeneration. ACS Biomater Sci Eng. Published online 2018. https://doi.org/10.1021/acsbiomaterials.8b00150 PMid:33434996
25. Wu R, Li H, Yang Y, Zheng Q, Li S, Chen Y. Bioactive Silk Fibroin-Based Hybrid Biomaterials for Musculoskeletal Engineering: Recent Progress and Perspectives. ACS Appl Bio Mater. Published online 2021. https://doi.org/10.1021/acsabm.1c00654 PMid:35006966
26. Zahedi P, Hassani Besheli N, Farokhi M, Mottaghitalab F, Sohrabi A, Ghorbanian SA. Silk Fibroin Nanoparticles Functionalized with Fibronectin for Release of Vascular Endothelial Growth Factor to Enhance Angiogenesis. J Nat Fibers. Published online 2022. https://doi.org/10.1080/15440478.2021.1982814
27. Grabska‐zielińska S, Sionkowska A. How to improve physico‐chemical properties of silk fibroin materials for biomedical applications?-blending and cross‐linking of silk fibroin-a review. Materials (Basel). Published online 2021. https://doi.org/10.3390/ma14061510 PMid:33808809 PMCid:PMC8003607
28. Abu Elella MH, Mohamed F, Abdel Gawad OF, Abdallah HM. Polymer nanocomposite films and coatings in the textile industry. Polym Nanocomposite Film Coatings. 2024;(January):631-662. https://doi.org/10.1016/B978-0-443-19139-8.00008-5
29. Melke J, Midha S, Ghosh S, Ito K, Hofmann S. Silk fibroin as biomaterial for bone tissue engineering. Acta Biomater. Published online 2016. https://doi.org/10.1016/j.actbio.2015.09.005 PMid:26360593
30. Montalbán MG, Coburn JM, Lozano-Pérez AA, Cenis JL, Víllora G, Kaplan DL. Production of curcumin-loaded silk fibroin nanoparticles for cancer therapy. Nanomaterials. Published online 2018. https://doi.org/10.3390/nano8020126 PMid:29495296 PMCid:PMC5853757
31. Ruiz MAA, Fuster MG, Martínez TM, et al. The Effect of Sterilization on the Characteristics of Silk Fibroin Nanoparticles. Polymers (Basel). Published online 2022. https://doi.org/10.3390/polym14030498 PMid:35160487 PMCid:PMC8840090
32. Ansary RH, Awang MB, Rahman MM. Biodegradable poly(D,L-lactic-co-glycolic acid)-based micro/nanoparticles for sustained release of protein drugs - A review. Trop J Pharm Res. Published online 2014. https://doi.org/10.4314/tjpr.v13i7.24
33. Wang Y, Kim BJ, Peng B, et al. Controlling silk fibroin conformation for dynamic, responsive, multifunctional, micropatterned surfaces. Proc Natl Acad Sci U S A. Published online 2019. https://doi.org/10.1073/pnas.1911563116 PMid:31591247 PMCid:PMC6815133
34. Pandey V, Haider T, Chandak AR, Chakraborty A, Banerjee S, Soni V. Surface modified silk fibroin nanoparticles for improved delivery of doxorubicin: Development, characterization, in-vitro studies. Int J Biol Macromol. Published online 2020. https://doi.org/10.1016/j.ijbiomac.2020.07.326 PMid:32758604
35. Gholipourmalekabadi M, Sapru S, Samadikuchaksaraei A, Reis RL, Kaplan DL, Kundu SC. Silk fibroin for skin injury repair: Where do things stand? Adv Drug Deliv Rev. Published online 2020. https://doi.org/10.1016/j.addr.2019.09.003 PMid:31678360
36. Tanaka K, Kajiyama N, Ishikura K, et al. Determination of the site of disulfide linkage between heavy and light chains of silk fibroin produced by Bombyx mori. Biochim Biophys Acta - Protein Struct Mol Enzymol. Published online 1999. https://doi.org/10.1016/S0167-4838(99)00088-6
37. Eisoldt L, Thamm C, Scheibel T. Review: The role of terminal domains during storage and assembly of spider silk proteins. Biopolymers. Published online 2012. https://doi.org/10.1002/bip.22006 PMid:22057429
38. Tong X, Pan W, Su T, Zhang M, Dong W, Qi X. Recent advances in natural polymer-based drug delivery systems. React Funct Polym. Published online 2020. https://doi.org/10.1016/j.reactfunctpolym.2020.104501
39. Florczak A, Grzechowiak I, Deptuch T, Kucharczyk K, Kaminska A, Dams-Kozlowska H. Silk particles as carriers of therapeutic molecules for cancer treatment. Materials (Basel). Published online 2020. https://doi.org/10.3390/ma13214946 PMid:33158060 PMCid:PMC7663281
40. Passi M, Kumar V, Packirisamy G. Theranostic nanozyme: Silk fibroin based multifunctional nanocomposites to combat oxidative stress. Mater Sci Eng C. Published online 2020. https://doi.org/10.1016/j.msec.2019.110255 PMid:31761203
41. Pham DT, Saelim N, Tiyaboonchai W. Design of experiments model for the optimization of silk fibroin based nanoparticles. Int J Appl Pharm. Published online 2018. https://doi.org/10.22159/ijap.2018v10i5.28139
42. Kolev A, Vassileva V, Radev L. Antibacterial fibroin / alginate blended biomaterials containing Silver and Ciprofloxacin. 2016;(December):1965-1971.
43. Liu Q, Liu H, Fan Y. Preparation of silk fibroin carriers for controlled release. Microsc Res Tech. Published online 2017. https://doi.org/10.1002/jemt.22606 PMid:26638113
44. Mottaghitalab F, Farokhi M, Shokrgozar MA, Atyabi F, Hosseinkhani H. Silk fibroin nanoparticle as a novel drug delivery system. J Control Release. Published online 2015. https://doi.org/10.1016/j.jconrel.2015.03.020 PMid:25797561
45. Jain A, Singh SK, Arya SK, Kundu SC, Kapoor S. Protein Nanoparticles: Promising Platforms for Drug Delivery Applications. ACS Biomater Sci Eng. Published online 2018. https://doi.org/10.1021/acsbiomaterials.8b01098 PMid:33418796
46. Fan C, Chen P, Liu X, et al. Use of the freeze salting-out method for reducing dosage of salting-out agent and salinity in wastewater from carmine production. Desalination. Published online 2020. https://doi.org/10.1016/j.desal.2020.114475
47. Hammad SF, Abdallah IA, Bedair A, Mansour FR. Salting-out induced liquid-liquid microextraction for alogliptin benzoate determination in human plasma by HPLC/UV. BMC Chem. Published online 2021. https://doi.org/10.1186/s13065-020-00729-8 PMid:33451337 PMCid:PMC7809805
48. Fu C, Li Z, Sun Z, Xie S. A review of salting-out effect and sugaring-out effect: driving forces for novel liquid-liquid extraction of biofuels and biochemicals. Front Chem Sci Eng. Published online 2021. https://doi.org/10.1007/s11705-020-1980-3
49. Nguyen TP, Nguyen QV, Nguyen VH, et al. Silk fibroin-based biomaterials for biomedical applications: A review. Polymers (Basel). Published online 2019. https://doi.org/10.3390/polym11121933 PMid:31771251 PMCid:PMC6960760
50. Pritchard EM, Kaplan DL. Silk fibroin biomaterials for controlled release drug delivery. Expert Opin Drug Deliv. 2011;8(6):797-811. https://doi.org/10.1517/17425247.2011.568936 PMid:21453189
51. Burke KA, Roberts DC, Kaplan DL. Silk Fibroin Aqueous-Based Adhesives Inspired by Mussel Adhesive Proteins. Biomacromolecules. Published online 2016. https://doi.org/10.1021/acs.biomac.5b01330 PMid:26674175 PMCid:PMC5765759
52. Pang L, Ming J, Pan F, Ning X. Fabrication of silk fibroin fluorescent nanofibers via electrospinning. Polymers (Basel). Published online 2019. https://doi.org/10.3390/polym11060986 PMid:31167377 PMCid:PMC6631164
53. Fuster MG, Carissimi G, Montalbán MG, Víllora G. Improving anticancer therapy with naringenin-loaded silk fibroin nanoparticles. Nanomaterials. Published online 2020. https://doi.org/10.3390/nano10040718 PMid:32290154 PMCid:PMC7221656
54. Yadav R, Purwar R. Influence of metal oxide nanoparticles on morphological, structural, rheological and conductive properties of mulberry silk fibroin nanocomposite solutions. Polym Test. Published online 2021. https://doi.org/10.1016/j.polymertesting.2020.106916
55. Carissimi G, Lozano-Pérez AA, Montalbán MG, Aznar-Cervantes SD, Cenis JL, Víllora G. Revealing the influence of the degumming process in the properties of silk fibroin nanoparticles. Polymers (Basel). Published online 2019. https://doi.org/10.3390/polym11122045 PMid:31835438 PMCid:PMC6960545
56. Prakash NJ, Mane PP, George SM, Kandasubramanian B. Silk Fibroin As an Immobilization Matrix for Sensing Applications. ACS Biomater Sci Eng. Published online 2021. https://doi.org/10.1021/acsbiomaterials.1c00080 PMid:33861079
57. Lv S. Silk Fibroin-Based Materials for Catalyst Immobilization. Molecules. Published online 2020. https://doi.org/10.3390/molecules25214929 PMid:33114465 PMCid:PMC7663501
58. Hcini K, Lozano-Pérez AA, Cenis JL, Quílez M, Jordán MJ. Extraction and encapsulation of phenolic compounds of tunisian rosemary (Rosmarinus officinalis l.) extracts in silk fibroin nanoparticles. Plants. Published online 2021. https://doi.org/10.3390/plants10112312 PMid:34834676 PMCid:PMC8618009
59. Darshan GH, Kong D, Gautrot J, Vootla SK. Fabrication and Characterization of Conductive Conjugated Polymer-Coated Antheraea mylitta Silk Fibroin Fibers for Biomedical Applications. Macromol Biosci. Published online 2017. https://doi.org/10.1002/mabi.201600443 PMid:28240813
60. Das S, Ghosh B, Sarkar K. Nanocellulose as sustainable biomaterials for drug delivery. Sensors Int. Published online 2022. https://doi.org/10.1016/j.sintl.2021.100135
61. Fei X, Jia M, Du X, et al. Green synthesis of silk fibroin-silver nanoparticle composites with effective antibacterial and biofilm-disrupting properties. Biomacromolecules. 2013;14(12):4483-4488. https://doi.org/10.1021/bm4014149 PMid:24171643
62. Mann JE, Gao R, London SS, Swift JA. Desolvation Processes in Channel Solvates of Niclosamide. Mol Pharm. Published online 2023. https://doi.org/10.1021/acs.molpharmaceut.3c00481 PMid:37850910 PMCid:PMC10630950
63. Weber C, Coester C, Kreuter J, Langer K. Desolvation process and surface characterisation of protein nanoparticles. Int J Pharm. Published online 2000. https://doi.org/10.1016/S0378-5173(99)00370-1 PMid:10601688
64. Wang A, Wang L, Wu Y, et al. Uncovering the Effect of Solid Electrolyte Interphase on Ion Desolvation for Rational Interface Design in Li-Ion Batteries. Adv Energy Mater. Published online 2023. https://doi.org/10.1002/aenm.202300626
65. Xu S, Chen S, Zhang F, et al. Preparation and controlled coating of hydroxyl-modified silver nanoparticles on silk fibers through intermolecular interaction-induced self-assembly. Mater Des. 2016;95:107-118. https://doi.org/10.1016/j.matdes.2016.01.104
66. Yang Z, Peng H, Wang W, Liu T. Crystallization behavior of poly(ε-caprolactone)/layered double hydroxide nanocomposites. J Appl Polym Sci. 2010;116(5):2658-2667. https://doi.org/10.1002/app.31787
67. Simončič B, Klemenčič D. Preparation and performance of silver as an antimicrobial agent for textiles: A review. Text Res J. 2016;86(2):210-223. https://doi.org/10.1177/0040517515586157
68. Pandiarajan J, Krishnan M. Properties, synthesis and toxicity of silver nanoparticles. Environ Chem Lett. 2017;15(3):387-397. https://doi.org/10.1007/s10311-017-0624-4
69. Calamak S, Aksoy EA, Erdogdu C, Sagıroglu M, Ulubayram K. Silver nanoparticle containing silk fibroin bionanotextiles. J Nanoparticle Res. 2015;17(2). https://doi.org/10.1007/s11051-015-2895-7
70. Shrivastava S, Bera T, Roy A, Singh G, Ramachandrarao P, Dash D. Characterization of enhanced antibacterial effects of novel silver nanoparticles. Nanotechnology. 2007;18(22). https://doi.org/10.1088/0957-4484/18/22/225103 PMid:37016550
71. Pei Z, Sun Q, Sun X, Wang Y, Zhao P. Preparation and characterization of silver nanoparticles on silk fibroin/carboxymethy lchitosan composite sponge as anti-bacterial wound dressing. Biomed Mater Eng. 2015;26:S111-S118. https://doi.org/10.3233/BME-151296 PMid:26405868
72. Lammel AS, Hu X, Park SH, Kaplan DL, Scheibel TR. Controlling silk fibroin particle features for drug delivery. Biomaterials. 2010;31(16):4583-4591. https://doi.org/10.1016/j.biomaterials.2010.02.024 PMid:20219241 PMCid:PMC2846964
73. Xu S, Song J, Morikawa H, Chen Y, Lin H. Fabrication of hierarchical structured Fe3O4 and Ag nanoparticles dual-coated silk fibers through electrostatic self-assembly. Mater Lett. 2015;164(October):274-277. https://doi.org/10.1016/j.matlet.2015.08.051
74. Jaworek A, Sobczyk AT. Electrospraying route to nanotechnology: An overview. J Electrostat. Published online 2008. https://doi.org/10.1016/j.elstat.2007.10.001
75. Sridhar R, Ramakrishna S. Electrosprayed nanoparticles for drug delivery and pharmaceutical applications. Biomatter. 2013;3(3):37-41. https://doi.org/10.4161/biom.24281 PMid:23512013 PMCid:PMC3749275
76. Aseh A, Ríos CN. <Gupta V-IJN.pdf>. Published online 2009:115-122.
77. Dhas SP, Anbarasan S, Mukherjee A, Chandrasekaran N. Biobased silver nanocolloid coating on silk fibers for prevention of post-surgical wound infections. Int J Nanomedicine. 2015;10:159-170. https://doi.org/10.2147/IJN.S82211 PMid:26491317 PMCid:PMC4599606
78. Bhat PN, Nivedita S, Roy S. Use of sericin of Bombyx mori in the synthesis of silver nanoparticles, their characterization and application. Indian J Fibre Text Res. 2011;36(2):167-171.
79. Lu Z, Meng M, Jiang Y, Xie J. UV-assisted in situ synthesis of silver nanoparticles on silk fibers for antibacterial applications. Colloids Surfaces A Physicochem Eng Asp. 2014;447:1-7. https://doi.org/10.1016/j.colsurfa.2014.01.064
80. Seib FP, Jones GT, Rnjak-Kovacina J, Lin Y, Kaplan DL. pH-Dependent Anticancer Drug Release from Silk Nanoparticles. Adv Healthc Mater. 2013;2(12):1606-1611. https://doi.org/10.1002/adhm.201300034 PMid:23625825 PMCid:PMC3808531
81. Choi YJ, Cho DW, Lee H. Development of Silk Fibroin Scaffolds by Using Indirect 3D-Bioprinting Technology. Micromachines. Published online 2022. https://doi.org/10.3390/mi13010043 PMid:35056208 PMCid:PMC8779165
82. Carullo D, Carpentieri S, Ferrari G, Pataro G. Influence of mechanical comminution of raw materials and PEF treatment on the aqueous extraction of phenolic compounds from artichoke wastes. J Food Eng. Published online 2024. https://doi.org/10.1016/j.jfoodeng.2024.111939
83. Patil RA, Deshannavar UB. To study the effect of mechanical comminution on lignin percentage and calorific value of dry sugar cane leaves. In: Materials Today: Proceedings. ; 2018. https://doi.org/10.1016/j.matpr.2018.06.149
84. Subia B, Chandra S, Talukdar S, Kundu SC. Folate conjugated silk fibroin nanocarriers for targeted drug delivery. Integr Biol (United Kingdom). Published online 2014. https://doi.org/10.1039/C3IB40184G PMid:24345855
85. Gianak O, Pavlidou E, Sarafidis C, Karageorgiou V, Deliyanni E. Silk fibroin nanoparticles for drug delivery: Effect of bovine serum albumin and magnetic nanoparticles addition on drug encapsulation and release. Separations. Published online 2018. https://doi.org/10.3390/separations5020025
86. Srisuwan Y, Srihanam P, Baimark Y. Preparation of silk fibroin microspheres and its application to protein adsorption. J Macromol Sci Part A Pure Appl Chem. 2009;46(5):521-525. https://doi.org/10.1080/10601320902797780
87. Reddy A H, B V. Synthesis of Silk Silver Nanoparticles form Silkworm Cocoons and Their Antibacterial Activity on Methicillin Resistant Staphylococcus aureus (MRSA) and Escherichia coli. J Nanomed Nanotechnol. 2017;08(04):8-10. https://doi.org/10.4172/2157-7439.1000453
88. Marin M. Tuning and Optimization of Silk Fibroin Gels for Biomedical Applications. T Virginia Commonw Univ. 2014;Ms(2014-4):55.
89. Bailey K. Potential Applications of Silk Fibroin as a Biomaterial. Published online 2013:137. https://uwspace.uwaterloo.ca/bitstream/handle/10012/7621/Bailey_Kevin.pdf?sequence=1
90. Crescent R, Tower B, Road AEG, Name P, Mustafa M. Non-Government Teachers ' Registration & Certification Authority ( NTRCA ) 17th Teachers ' Registration Exam 2020 Candidate ' s Information Form ( CIF ) User ID : TZEYKS Exam Centre : Academic Qua. Published online 2020:17-18.
91. Shi P, Goh JCH. Release and cellular acceptance of multiple drugs loaded silk fibroin particles. Int J Pharm. 2011;420(2):282-289. https://doi.org/10.1016/j.ijpharm.2011.08.051 PMid:21920418
92. Yan HB, Zhang YQ, Ma YL, Zhou LX. Biosynthesis of insulin-silk fibroin nanoparticles conjugates and in vitro evaluation of a drug delivery system. J Nanoparticle Res. 2009;11(8):1937-1946. https://doi.org/10.1007/s11051-008-9549-y
93. Cao Z, Chen X, Yao J, Huang L, Shao Z. The preparation of regenerated silk fibroin microspheres. Soft Matter. 2007;3(7):910-915. https://doi.org/10.1039/b703139d PMid:32900086
94. Kundu B, Rajkhowa R, Kundu SC, Wang X. Silk fibroin biomaterials for tissue regenerations. Adv Drug Deliv Rev. 2013;65(4):457-470. https://doi.org/10.1016/j.addr.2012.09.043 PMid:23137786
95. Liu B, Song Y wei, Jin L, et al. Silk structure and degradation. Colloids Surfaces B Biointerfaces. Published online 2015. https://doi.org/10.1016/j.colsurfb.2015.04.040 PMid:25982316
96. Mathur AB, Gupta V. Silk fibroin-derived nanoparticles for biomedical applications. Nanomedicine. 2010;5(5):807-820. https://doi.org/10.2217/nnm.10.51 PMid:20662650
97. Zhao M, Qi Z, Tao X, Newkirk C, Hu X, Lu S. Chemical, thermal, time, and enzymatic stability of silk materials with silk i structure. Int J Mol Sci. Published online 2021. https://doi.org/10.3390/ijms22084136 PMid:33923636 PMCid:PMC8073524
98. Bandyopadhyay A, Chowdhury SK, Dey S, Moses JC, Mandal BB. Silk: A Promising Biomaterial Opening New Vistas Towards Affordable Healthcare Solutions. J Indian Inst Sci. Published online 2019. https://doi.org/10.1007/s41745-019-00114-y
99. Hori K, Wada A STC. NII-Electronic Library Service. Chem Pharm Bull. 1970;(43):2091. http://www.mendeley.com/research/geology-volcanic-history-eruptive-style-yakedake-volcano-group-central-japan/
100. Wang J, Yang S, Li C, et al. Nucleation and Assembly of Silica into Protein-Based Nanocomposites as Effective Anticancer Drug Carriers Using Self-Assembled Silk Protein Nanostructures as Biotemplates. ACS Appl Mater Interfaces. Published online 2017. https://doi.org/10.1021/acsami.7b05664 PMid:28665103 PMCid:PMC5759309
101. Srisuwan Y, Srihanam P, Baimark Y. Preparation of silk fibroin microspheres and its application to protein adsorption. J Macromol Sci Part A Pure Appl Chem. 2009;46(5):521-525. https://doi.org/10.1080/10601320902797780
102. Tran HA, Hoang TT, Maraldo A, et al. Emerging silk fibroin materials and their applications: New functionality arising from innovations in silk crosslinking. Mater Today. Published online 2023. https://doi.org/10.1016/j.mattod.2023.03.027
103. Sridhar R, Ramakrishna S. Electrosprayed nanoparticles for drug delivery and pharmaceutical applications. Biomatter. 2013;3(3):37-41. https://doi.org/10.4161/biom.24281 PMid:23512013 PMCid:PMC3749275
104. Li J, Li S, Huang J, et al. Spider Silk-Inspired Artificial Fibers. Adv Sci. Published online 2022. https://doi.org/10.1002/advs.202103965 PMid:34927397 PMCid:PMC8844500
105. Reddy A H, B V. Synthesis of Silk Silver Nanoparticles form Silkworm Cocoons and Their Antibacterial Activity on Methicillin Resistant Staphylococcus aureus (MRSA) and Escherichia coli. J Nanomed Nanotechnol. 2017;08(04):8-10. https://doi.org/10.4172/2157-7439.1000453
106. Bodea A, Leucuta SE. Optimization of propranolol hydrochloride sustained release pellets using a factorial design. Int J Pharm. Published online 1997. https://doi.org/10.1016/S0378-5173(97)00114-2
107. Marin M. Tuning and Optimization of Silk Fibroin Gels for Biomedical Applications. T Virginia Commonw Univ. 2014;Ms(2014-4):55.
108. Asakura T. Structure of Silk I (Bombyx mori Silk Fibroin before Spinning) -Type II β-Turn, Not α-Helix. Molecules. Published online 2021. https://doi.org/10.3390/molecules26123706 PMid:34204550 PMCid:PMC8234240
109. Bailey K. Potential Applications of Silk Fibroin as a Biomaterial. Published online 2013:137. https://uwspace.uwaterloo.ca/bitstream/handle/10012/7621/Bailey_Kevin.pdf?sequence=1
110. Whittall DR, Baker K V., Breitling R, Takano E. Host Systems for the Production of Recombinant Spider Silk. Trends Biotechnol. Published online 2021. https://doi.org/10.1016/j.tibtech.2020.09.007 PMid:33051051
111. Crescent R, Tower B, Road AEG, Name P, Mustafa M. Non-Government Teachers ' Registration & Certification Authority ( NTRCA ) 17th Teachers ' Registration Exam 2020 Candidate ' s Information Form ( CIF ) User ID : TZEYKS Exam Centre : Chattogram Mailing / Present Address : Permanent Address : Academic Qua. Published online 2020:17-18.
112. Verma D, Gulati N, Kaul S, Mukherjee S, Nagaich U. Protein Based Nanostructures for Drug Delivery. J Pharm. 2018;2018:1-18. https://doi.org/10.1155/2018/9285854 PMid:29862118 PMCid:PMC5976961
113. Shi P, Goh JCH. Release and cellular acceptance of multiple drugs loaded silk fibroin particles. Int J Pharm. 2011;420(2):282-289. https://doi.org/10.1016/j.ijpharm.2011.08.051 PMid:21920418
114. Shivananda CS, Madhu Kumar R, Narayana B, et al. Preparation and characterisation of silk fibroin-silver nanoparticles (SF-AgNPs) composite films. Mater Res Innov. 2017;21(4):210-214. https://doi.org/10.1080/14328917.2016.1200844
115. Yan HB, Zhang YQ, Ma YL, Zhou LX. Biosynthesis of insulin-silk fibroin nanoparticles conjugates and in vitro evaluation of a drug delivery system. J Nanoparticle Res. 2009;11(8):1937-1946. https://doi.org/10.1007/s11051-008-9549-y
116. Wang Z, Wang Z, Lu WW, Zhen W, Yang D, Peng S. Novel biomaterial strategies for controlled growth factor delivery for biomedical applications. NPG Asia Mater. 2017;9(10):e435-17. https://doi.org/10.1038/am.2017.171
117. Cao Z, Chen X, Yao J, Huang L, Shao Z. The preparation of regenerated silk fibroin microspheres. Soft Matter. 2007;3(7):910-915. https://doi.org/10.1039/b703139d PMid:32900086
118. Meinel L, Kaplan DL. Silk constructs for delivery of musculoskeletal therapeutics. Adv Drug Deliv Rev. 2012;64(12):1111-1122. https://doi.org/10.1016/j.addr.2012.03.016 PMid:22522139 PMCid:PMC3719414
119. Kundu B, Rajkhowa R, Kundu SC, Wang X. Silk fibroin biomaterials for tissue regenerations. Adv Drug Deliv Rev. 2013;65(4):457-470. https://doi.org/10.1016/j.addr.2012.09.043 PMid:23137786
120. Qi Y, Wang H, Wei K, et al. A review of structure construction of silk fibroin biomaterials from single structures to multi-level structures. Int J Mol Sci. 2017;18(3). https://doi.org/10.3390/ijms18030237 PMid:28273799 PMCid:PMC5372488
121. Liu B, Song Y wei, Jin L, et al. Silk structure and degradation. Colloids Surfaces B Biointerfaces. Published online 2015. https://doi.org/10.1016/j.colsurfb.2015.04.040 PMid:25982316
122. Kundu J, Chung Y Il, Kim YH, Tae G, Kundu SC. Silk fibroin nanoparticles for cellular uptake and control release. Int J Pharm. 2010;388(1-2):242-250. https://doi.org/10.1016/j.ijpharm.2009.12.052 PMid:20060449
123. Mathur AB, Gupta V. Silk fibroin-derived nanoparticles for biomedical applications. Nanomedicine. 2010;5(5):807-820. https://doi.org/10.2217/nnm.10.51 PMid:20662650
124. Zhao M, Qi Z, Tao X, Newkirk C, Hu X, Lu S. Chemical, thermal, time, and enzymatic stability of silk materials with silk i structure. Int J Mol Sci. Published online 2021. https://doi.org/10.3390/ijms22084136 PMid:33923636 PMCid:PMC8073524
125. Mondal M, Trivedy K, Nirmal Kumar S. The silk proteins, sericin and fibroin in silkworm. Casp J Environ Sci. 2007;5(2):63-76.
126. Bandyopadhyay A, Chowdhury SK, Dey S, Moses JC, Mandal BB. Silk: A Promising Biomaterial Opening New Vistas Towards Affordable Healthcare Solutions. J Indian Inst Sci. Published online 2019. https://doi.org/10.1007/s41745-019-00114-y
127. Hori K, Wada A STC. NII-Electronic Library Service. Chem Pharm Bull. 1970;(43):2091. http://www.mendeley.com/research/geology-volcanic-history-eruptive-style-yakedake-volcano-group-central-japan/