Available online on 15.09.2026 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

Copyright  © 2026 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

Bilosomes: A specialized bile salt based nanocarrier drug delivery system in cancer therapy

Shagufta Rafik Shikalgar ¹, Natalin Marian Veg ¹,  Ashwini Ashok Delekar ¹,  Shreya Dilip Sangale ¹,  Vikas Basu Pawar ¹, Sunita Sakharam Shinde *²

1 Department of Pharmaceutics, Tatyasaheb Kore College of Pharmacy, Warananagar 416113, Maharashtra, India. 

2 Department of Pharmaceutics, Tatyasaheb Kore College of Pharmacy, Warana University, Warananagar 416113, Maharashtra, India

 

 

Targeted drug delivery system is widely used platform for treating various disease across the globe. Drug targeting concept was first coined by Paul Ehrlich a German scientist in the late 19^th and early 20^th centuries. This targeting approach is then terms as Magic bullet ¹. His study finally led to the discovery of arsphenamine in 1909, the first effective ‘targeted’ treatment for syphilis, which regarded as the practical implementation of his magic bullet notion and the basis for contemporary chemotherapy ². Drug targeting enables the medicine to reach its target site and produce the desired pharmacological reaction as per the therapeutic necessity.  A precise grasp of the level of targeting makes it simple to select the appropriate targeting moiety, ligand, or carrier system ³.   Furthermore, focused delivery enables for a minimal amount of medicine to reach non target organs and tissues, resulting in an effective and safe drug delivery system ⁴. A carrier system can be used to deliver medications in a targeted manner.  A carrier is a distinct molecule or system that is fundamentally required for the efficient delivery of a loaded drug to predetermined areas ⁵.  These are specially engineered vectors that transport medicine to the desired location by encapsulating or attaching to it with a spacer moiety. Drug carrier is nothing but the nanotechnology used in the targeting which involves liposomes, ethosomes, cubosomes, transferosomes, bilosomes, polymeric micelles and dendrimers ⁶. Targeted approach is highly suitable techniques as compared to traditional drug administration methods because this system reduces the systemic toxicity and lowers side effects as well as improve the bioavailability, accumulation of drug at targeted site which significantly improves the therapeutic index of drug ⁷.   

Bilosomes are emerged as a recent development of advanced targeted drug carrier or novel targeting approach based on bile salt and phospholipids which are nano carrier that created to get around some of the drawbacks of traditional liposomes , namely instability in the digestive system .Because of their extreme flexibility, they can encapsulated medications or genetic material to improve absorption, stability ,and targeted delivery via a variety of methods ,including oral, transdermal or ocular administration⁸. This is accomplished by the bile salts improving penetration through biological membranes and protecting the vesicles against deterioration. They are incorporated bile salts into the bilayer membrane. Bilosomes in particular enhance the stability and oral absorption of medications in GI malignancies ⁹. 

Bilosomes have several advantages over other targeting drug delivery systems such as more stability and biocompatibility due to presence of nonionic surfactant also Cholesterol to make the membrane stiff (Fig.1). Bile salts to improve penetration and provide stability against GI deterioration. High entrapment efficiency and capacity to deliver a range of mediation and biological substances. Bilosomes amphililic properties enable them to shield their contents from GI tract acid and enzymatic degradation, promoting excellent medication absorption when taken orally. By improving medication uptake and transport across epithelial barriers, bilosomes facilitate targeted distribution. They can be further modified foe better targeting and controlled release ¹⁰. Increased stability and resistance to GI breakdown when compared to traditional vesicles. Adaptability in delivery methods, including as oral, transdermal and mucosal ¹¹. The mechanism of bilosomes are involved bile salts change the characteristics of vesicular membranes by functioning as edge activators that improve fluidity, reduces surface tension ,and encourages tissue penetration¹². 

According to the World Health Organization (WHO), cancer is the leading cause of illness and death worldwide.  Between 2005 and 2020, an estimated 85 million people are expected to die from cancer ¹³.In September 2025 recent study shows that by 75% death rate expected to rise in next 25 years ¹⁴.  Patient morbidity and mortality rates are rarely reduced by the conventional chemotherapeutics used in cancer treatment.   This result is caused by the chemotherapeutics since they seriously damage healthy tissues.  One intriguing development in cancer treatment is the ability of nanoparticles to overcome resistance in cancer cells ¹⁵.   Research has looked into using nanoparticles as a possible drug delivery method to solve these issues in cancer treatment.  While simultaneously increasing the intracellular concentration of drugs within cancer cells, nanoparticles can protect healthy cells from harm ¹⁶. In order to improve pharmaceutical formulations and treatment approaches, the future will offer customized nanomedicine, artificial intelligence, and real-time imaging¹⁷ .One of the main objectives of cancer treatment is to target the specific cancer cells while sparing as many healthy cells as possible.  Chemotherapy administration is hampered by several significant clinical obstacles because of the wide body distribution, MDR mechanism, poor absorption, increased metabolism, excretion, and poor diffusion across the tumor mass ¹⁸. In this regard, improving nanoparticle absorption depends on EPR in solid tumors and the physiological drug resistance of the cancer micro environment ¹⁹. This enhancement was made possible by increasing encapsulation efficiency, using artificial intelligence algorithms to model nanocarrier drug release kinetics, and predicting interactions between drug incorporation, nanocarriers, cell membranes, and biological mediators ²⁰.

Hepatocellular carcinoma, breast cancer, colon cancer, melanoma and have all demonstrated encouraging outcomes when treated with bilosomes ²¹.Their longer circulation duration improves the like hood of targeting distant tumor location and invasive cells in metastatic malignancies and also in breast cancer ²². Both hydrophilic and hydrophobic anticancer medications are encapsulated in bilosomes, which increases their solubility and stability and boosts their therapeutic action and bioavailability ²³.  This review article involves potentially use of bilosomes as a targeting drug delivery system in various cancer types such as melanoma or skin cancer, hepatic or liver cancer, colon cancer, breast cancer also collectively study of mechanism of bilosomes.                 

The primary structural components of bilosomes formulation includes 

Bile salts: these are the key component of bilosomes system.  Common bile salts used are sodium deoxycholate (SDC), sodium Glycocholate (SGC), and sodium Taurocholate (STC). Bile salts are integrated into the phospholipid bilayers and nonionic surfactants 

Amphiphilic Lipids / Nonionic surfactants: These are Main framework of bilayer phospholipid membrane. Examples includes phospholipids like phosphatidylcholine and soybean and nonionic surfactants like span 60, 80 or tween 60, 80 etc. 

Cholesterol: This is important for maintain membrane fluidity and rigidity and hence it can effects permeability and stability bilosome structure.

                 

Figure 1: Structure of bilosomes

Figure 2: 3D structure of bilosomes

Figure 3: Bilosomes in targeted drug delivery

 

 

Figure 4: Bilosomes at tumor site

 

3.  MECHANISM OF ACTION OF BILOSOMES:

In the formulation of bilosomes the main ingredient is a bile salt. In below Table 1 various types of Bile salts are mentioned that also involving in treatment specifying related to cancer.

Table 1: Type of Bile salts used in Cancer

Sr.No	Bile Salt	Structure	pH	Cancer Treatment	Ref
	Sodium Deoxycholate	Steroid structure with 2 hydroxyl groups	pH >7	Colorectal and other cancers	24
	Deoxycholic acid	Steroid structure having 2 hydroxyl groups & 1 carboxyl group	pH~8.3	Breast and Colorectal	25
	Sodium Glycocholate	Glycine trihydroxyl sodium salt	pH 6-8	Lung cancer , liver cancer, skin cancer	26
	Sodium Chenodeoxycholate	Steroid nucleus , hydroxyls at C-3, C-7 positions	pH ~ 6.7	Colon & skin cancer	27
	Sodium Ursodeoxycholate	Epimerized CDCA at C-7, more hydrophilic	pH ~ 8	Gastric , liver and prostate cancer	28
	Sodium Taurocholate	Cholic acid steroid linked with amino acid taurine	pH 6-8	Colorectal cancer	29
	Sodium Taurodeoxycholate	Deoxycholic acid steroid with 2 OH group linked with amide-taurine bond	pH 6-8	Colorectal & Gastric Cancer	30
	Sodium cholate	Steroidal 3 OH & 1 COOH	pH 6-10	Liver & Pancreatic cancer , Breast cancer	31
	Conjugated Bile Salts	Glycerin/taurine conjugation increases solubility	pH 5.5-7	Liver  cancer	32
	Lithocholic Acid ( least commonly used salt farm)	Hydroxycholan-24-oic acid	Unstable / oxidize easily under acidic & neutral pH	Breast , pancreatic & prostate	32
	Tauro-chenodeoxycholic acid(TCDCA)	Dihydroxyl ethanesulfonic acid	p H 4.5-5	Gastric cancer	33

 

There are various preparation methods used to formulate Bilosomal nanoparticles. In below table 2 preparation methods are characterizes based on their advantages, disadvantages and types of cancer treated most. 

Table 2. Preparation methods of Bilosomes

There are primarily four to five methods used in the preparation of bilosomes which summarizes in below Table 2 with their advantages and disadvantages.

 

 

5. ROLE OF BILOSOMES IN CANCER

5.1 Liver cancer or Hepatocarcinoma 

Primary liver cancer is a condition characterized by the formation of malignant (cancer) cells in liver tissues³⁹. Bilosomes in liver cancer treatment serve as advanced nanocarrier, improving anticancer agent oral delivery and therapeutic efficacy.  These bilosomes are frequently coated with lactoferrin (LF) to allow active targeting, as LF can bind to receptors overexpressed on HCC cells, such as glycoprotein receptors, hence increasing cellular internalization⁴⁰. The mechanism consists of passive targeting via the increased permeability and retention (EPR) effect and active targeting via LF receptor-mediated endocytosis ⁴¹.The bilosomal formulation increases stability, bioavailability, and targeted administration to liver cancer cells, resulting in enhanced death via caspase-3 activation. This results in much better anticancer potency than free medicines, with a noticeable increase in tumor cell cytotoxicity without increased damage to normal cells ⁴². Bilosomes are a promising oral drug delivery strategy for liver cancer because they improve targeting, cellular uptake, and therapeutic results through both passive and active mechanisms, using particular ligands⁴³.

5.2 Lung Cancer 

Lung cancer is a condition characterized by uncontrolled cell proliferation in the lungs⁴⁴.  It was considered relatively rare in the early twentieth century, but by the end of the century, it had become the top cause of cancer-related death among males in more than 25 developed countries.  Bilosomes have showed promise as nanocarrier in lung cancer treatment, enhancing drug delivery and efficacy⁴⁵. Their mode of action in lung cancer mostly involves increasing drug permeability and cellular uptake, which results in enhanced cytotoxicity against lung cancer cells^. For example, piceatannol-loaded bilosome-zein protein formulations (PIC-BZ) had much stronger lethal effects on A549 lung cancer cells than the pure drug ⁴⁶.  By boosting caspase-3 protein expression, this formulation increased medication absorption while also inducing cell cycle arrest in the G2-M phase and apoptosis ⁴⁷. Similarly, bilosomes loaded with medications such as trametinib demonstrated enhanced penetration and cytotoxicity against lung cancer cells, as well as increased apoptotic activity when compared to the drug alone⁴⁸. In summary, bilosomes operate as effective nanocarriers in lung cancer by improving anticancer drug delivery, cellular uptake, and apoptosis-inducing properties, resulting in better treatment outcomes in lung cancer models such as the A549 cell line ⁴⁹

5.3 Breast Cancer: 

Breast cancer is leading cause of cancer deaths among women globally, rate vary by fivefold over the world, but they are increasing in areas where the disease was formerly uncommon. Nanotechnology is utilized to diagnose molecular cancer through the use of biomarker and nanoparticles, resulting in multivalent effect that increases specificity and binding affinity, making them an appropriate diagnostic agent⁵⁰.  Bilosomes have demonstrated promising efficacy in breast cancer treatment as drug delivery vehicles. They improve the absorption and targeting of anticancer medicines while minimizing side effects and treatment resistant^.   Bilosomes have been investigated for transdermal delivery of tamoxifen to the breast, which improves local drug concentration while reducing systematic side effects compared to oral treatment ⁵¹. According to recent study, bilosomes loaded with medications such as axitinib and methotrexate cause higher cytotoxicity and apoptosis in breast cancer cell lines such as MF7, showing increased anticancer activity ⁵². Bilosomal formulations improves drug stability, allow for controlled release penetration, resulting in greater therapeutic efficiency.

 

 

5.4 Skin cancer:

Skin cancer is an abnormal development of skin cells that is most commonly induced by exposure to ultraviolet radiation from sunlight or tanning beds. The most prevalent forms include basal cell carcinoma, squamous cell carcinoma and melanoma ⁵³. Bilosomes improved skin penetration and shield encapsulated medications or photosensitizing from deterioration^. Bilosomes have been shown in recent research to be efficient transporters of photosensitizers and anticancer drugs in skin cancer, particularly metastatic melanoma. For example, niosomes containing a mix of natural carotenoids (astaxanthin) and second – generation photosensitizers (such as Rose Bengal) have demonstrated potent antitumor effectiveness against human melanoma cell lines ⁵⁵. By dramatically decreasing cancer cell viability upon light activation, inducing apoptosis by modifying pro and anti-apoptosis proteins, and decreasing metastasis, these formulations make use of photodynamic treatment (PDT) ⁵⁶. Their surface characterization and Nano scale (size less than 100 nm) enable cellular absorption and transdermal administration. They target cancer cell more successfully than free medications, increasing selectivity and lowering toxicity ^57-58. Bilosomes offer regulated activation and synergistic anticancer effects, such as melanoma cell death and mitochondrial damage, when used in conjugation with photodynamic therapy ⁵⁹. By improving delivery and therapeutic efficacy, this novel bilosomes based method shows great promise a skin cancer therapy alternatives, particularly for difficult melanoma cases.

Bilosomes are comparatively more efficient and stable formulation among other nanoparticles or nano formulations. In Table 3 comparatively study are described between Bilosomes and traditional Nano formulations like liposomes or niosomes focuses mainly on important features.

 

 

Table 3: Comparative study of bilosomes with other nanotechnology

 

Bilosomes   require comprehensive characterization to evaluate their size , stability , charge , Morphology and drug loading for effective drug delivery applications⁶²  Common parameters are mentioned in below Table 4.

 

Table 4: Characterization of Bilosomes 

Parameter	Description	Typical Methods
Particle Size	Measures vesicle diameter distribution	Dynamic Light Scattering (DLS)
Polydispersity  Index (PDI)	Indicates Size Uniformity	DLS
Zeta Potential	Assesses Surface charge and stability	Zeta sizer
Entrapment Efficiency (%EE)	% of drug encapsulated	Centrifugation
Morphology	Vesicle shape and lamellarity	Transmission Electron Microscopy (TEM)

 

 

Bilosomes, as novel drug delivery nanocarriers offers advantages for cancer treatment, but their regulatory pathway present specific complexities. Bilosome components, which are often bile salts and phospholipids, are widely acknowledged as safe, biodegradable, and biocompatible, indicating that they are pharmaceutically acceptable ⁶³ that are summarized in Table 5 .

Bilosomes and other lipid-based drug delivery systems, are subject to the same regulatory scrutiny as nanocarriers by agencies such as the US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) to established efficacy and safety, these nanocarriers must be thoroughly characterized, tested for toxicity and validated clinically⁶⁴. Regulatory guidance mandates comprehensive evaluation through in vitro and in vivo toxicological studies to address potential risks and to ensure patient safety ⁶⁵. 

 

 

Table 5: Regulatory bodies and their role in regulation 

 

 

9. CASE STUDIES: 

9.1 Breast Cancer:

1. Zafar A et al., designed Lute Olin loaded Peglyated bilosome using thin-film hydration method and optimized them for enhanced anti-cancer activity. The percentage entrapment efficiency, particle size, poly-dispersity index, and zeta potential were found to be ‘75.05±0.65%, 252.24±3.54nm, 0.24, 32mV’ respectively. In vitro antioxidant activity of the Luteolin loaded pegylated bilosome compared to free drug was found to be 96.87±3.32% and 70.31±2.11% respectively. In cytotoxicity testing, the IC₅₀ value of the Luteolin loaded Peglyated bilosome was found to be 390mM and 510 mM against MCF7 and MDA-MB-231 cancer cells, respectively at 48 h. In cytotoxicity testing, the IC₅₀ value of Luteolin loaded Peglyated bilosome was found to be 370 µM and 510 µM whereas that of the free drug was 820 µM and 980 µM against MCF7 and MDA-MB-231 cancer cells, respectively at 48 h, demonstrating that luteolin loaded pegylated bilosome had a lower IC₅₀ value than the free drug . Overall, the results of the study indicated that luteolin loaded pegylated bilosome are promising in the treatment of Breast cancer ⁶⁷.

2. Zaki I et al., developed acrylamide derivatives loaded Peglyated bilosomes using the thin-film hydration method and optimized them for enhanced anti-cancer activity against ‘MCF-7’ breast cancer cells. The percentage entrapment efficiency, particle size and zeta potential, of optimized formulation were found to be ‘100 5.6%, 280.3 15.4 nm, 22.5 3.4 mv’ respectively. In cytotoxicity testing, the IC₅₀ value of acrylamide derivatives loaded Peglyated bilosomes compared to that of the free drug was 0.75 0.03 µM and 2.11 0.19 M respectively against MCF7 indicating that acrylamide derivatives loaded Peglyated bilosomes had a lower IC₅₀ value than the free drug. The findings of this study show that acrylamide derivatives loaded Peglyated bilosomes significantly better approach in the treatment of Breast cancer ⁶⁸.

9.2 Lung Cancer:

1. Alhakamy NA et al., Formulated Piceatannol-Loaded Bilosome Stabilized Zein Protein using the thin-film hydration method and optimized them for enhanced anticancer efficacy. The percentage entrapment efficiency and particle size were found to be 93.14 2.15% and 157.45 1.62 nm respectively. . In cytotoxicity testing, the IC₅₀ value of the pure Piceatannol and Piceatannol-Loaded Bilosome Stabilized zeta potential was found to be 22.3±3.4 µM and 5.78±2.3 µM respectively against A549 lung cancer cell line demonstrating that Piceatannol-Loaded Bilosome Stabilized Zein Protein had a lower IC₅₀ value than the free Piceatannol. The wound coverage of free Piceatannol and Piceatannol-Loaded Bilosome Stabilized Zein 59.64%, and 35.87% respectively. Overall, the study revealed that Piceatannol-Loaded Bilosome Stabilized Zein Protein are highly promising for improving the oral bioavailability and anticancer efficacy of Piceatannol in lung cancer treatment ⁴⁶.

 2. Chettupalli A. et al., designed Trametinib-loaded nano-bilosomes using the thin-film hydration method and optimized them for enhanced anticancer efficacy. The percentage entrapment efficiency, particle size, poly-dispersity index, and zeta potential were found to be 94.27 ± 2.16%, 158.32 ± 10.24 nm, 0.132 ± 0.03, and −46.57 ± 1.06 mV respectively. Ex vivo permeation studies revealed free drug and Trametinib-loaded nano-bilosomes solution exhibited 89.36 ± 4.95 µg and 1159.36 ± 4.81 µg permeation respectively which indicated markedly higher intestinal permeability and penetration compared to pure Trametinib. In cytotoxicity testing, the IC₅₀ value of the pure Trametinib and Trametinib-loaded nano-bilosomes was found to be 28.61 ± 3.56 µM and 9.74 ± 1.52 µM respectively demonstrating that Trametinib-loaded nano-bilosomes had a lower IC₅₀ value than the free Trametinib. Overall, the study revealed that Trametinib-loaded nano-bilosomes are highly promising for improving the oral bioavailability and anticancer efficacy of Trametinib in lung cancer treatment ^69.

9.3 Liver Cancer:

1. Kharouba M et al., developed Pitavastatin loaded bilosomes using the thin-film hydration method and optimized them for treatment of hepatocellular carcinoma. The percentage entrapment efficiency, particle size, poly-dispersity index, and zeta potential were found to be ‘90.56% ± 3.22, 112.28 nm ± 6.35, 0.229 ± 0.06, −7.86 mV ± 1.13’ respectively. In a comparative cytotoxicity investigation lactoferrin coated Pitavastatin loaded bilosomes exhibited IC₅₀ values of 2.82 μg/mL and 39.8 μg/mL whereas free drug solution exhibited IC₅₀ values of 124.9 μg/mL and 169 μg/mL against 2D HepG2 cancer cells, 3D HepG2 spheroids respectively which indicated superior selective anticancer activity. The In vivo studies demonstrated LF-coated PIT-loaded bilosomes produced the strongest anticancer effect, with 3-fold decrease tumor size and increasing caspase-3 expression by 4 to 5-fold. Generally, the study revealed that Pitavastatin loaded bilosomes are highly promising for improving the oral bioavailability and anticancer efficacy of Pitavastatin in treatment of hepatocellular carcinoma^14.

2. Abbas H et al., designed cur cumin analog nano-bilosomes using the thin-film hydration method and optimized them for treatment of hepatocellular carcinoma. The percentage entrapment efficiency, particle size, poly-dispersity index, and zeta potential were found to be ‘90.21 ± 1.0%, 111.6 ± 1.4 nm, 0.006, 27.05 ± 1.08mV’ respectively. In a comparative cytotoxicity investigation, PIP-loaded bilosomes and cur cumin suspension exhibited showed an IC₅₀ of 0.0895 µg/mL and 0.346 µg/mL against Huh-7 hepatocellular carcinoma cells indicating superior anticancer potency of the bilosomal formulation. The in-vivo safety study demonstrated that PIP-loaded bilosomes were significantly less toxic to normal Wi-38 cells with an IC₅₀ of 37.64 µg/mL compared to curcumin suspension and doxorubicin with 6.56 µg/mL and 2.02 µg/mL respectively. Overall, the study revealed that PIP-loaded bilosomes are highly promising for improving the solubility, selectivity, and anticancer efficacy of cur cumin analogs in hepatocellular carcinoma treatment ^70.

9.4 Skin Cancer:

1. Waglewska E et al., formulated Rose Bengal (RB) and Astaxanthin (AST) co-loaded positively charged bilosomes using the thin-film hydration method followed by sonication and optimized them for melanoma therapy. The particle size, poly-dispersity index, and zeta potential were found to be ‘69 ± 1 nm, 0.29 ± 0.01, +44 ± 1 mV’ respectively with entrapment efficiency of ‘85 ± 3%’ and ‘95 ± 2%’ for RB and AST respectively. In vitro cytotoxicity study was carried out using A375 and Me45 melanoma cells exhibited 20% and 30% reduction in viability against A375 and Me45 cell line respectively while maintaining >80% viability in normal HaCaT cells, confirming strong and selective photo cytotoxicity. Overall, the study indicated that Rose Bengal and Astaxanthin loaded cationic bilosomes represent a promising and biocompatible nano photodynamic platform with superior tumor-selective activity for melanoma treatment ⁵⁴.

10. LIMITATIONS:

Bilosomes, or bile salt incorporated nanocarriers like liposomes, have numerous significant drawbacks in drug delivery applications. These issues have an impact on the formulations, stability and performance.

Anionic hydrophilic medicines frequently move to the exterior aqueous space, lowering %EE. 

A negative charge on bile salts makes it difficult to incorporate certain drug^.

Bilosomes are more sensitive to preparation conditions, influencing vesicle size and stability. High production costs and challenges in large scale manufacturing hinder commercial viability. Capable production using micro fluidization remains challenging, as do long-term stability challenges such as aggregation and regulatory gaps for clinical approval. Safety profiling and clinical studies are required for human validation ⁷¹.

There is poor association between in vivo and in vitro models that simulated GI conditions. This leads to more difficult to accurately characterize and anticipate real world behavior^. 

11. FUTURE DIRECTIONS:

Bilosomes a bile salt-stabilized vesicular nanocarriers hold significant promise for drug delivery due to their enhanced stability relative to liposomes and niosomes, particularly via oral, transdermal, and mucosal routes. A 2025 study highlights their potential to improve bioavailability, enable targeted drug delivery, and support vaccine administration.

Bilosomes are particularly effective for the oral delivery of peptides, proteins, and biologics, as they resist gastrointestinal degradation and enhance absorption. They facilitate anticancer targeting through ligand modifications such as folic acid conjugation, reduce toxicity associated with anti-inflammatory medications, and support ophthalmic, nasal, and vaccine applications through controlled release mechanisms. While polymer incorporation improves stability and mucoadhesion, nano sized bilosomes enhance tissue penetration and cellular uptake. In the context of oncology, bilosomes are emerging as a viable nanocarrier platform for cancer therapy, offering enhanced stability. Targeted tumor delivery, and improved bioavailability of anticancer drugs compared to free drug formulations. Preclinical studies have demonstrated superior cytotoxic and pro apoptotic effects in colon, breast, and lung cancer cells relative to conventional treatments. These vesicles protect drugs from gastrointestinal degradation, enable precise targeting of cancer cells via bile salt receptors, and reduce systemic toxicity through strategies such as PEGylation and ligand modification. Potential applications extend to gastrointestinal malignancies, melanoma, and solid tumors requiring stimuli responsive drug release.

12. CONCLUSION:

Bilosomes are emerging as a promising nanocarrier platform for cancer therapy, offering enhanced stability, targeted tumor delivery, and improved bioavailability of anticancer drug compared to free drug formulations. Preclinical studies have demonstrated superior cytotoxic and pro- apoptotic effects in colon, breast, and lung cancer cells relative to conventional treatments. These vesicles protect drugs from gastrointestinal degradation, enables precise targeting of cancer cells via bile salt receptors, and reduce systemic toxicity through strategies such as PEGylation and ligand modification. Potential applications include gastrointestinal malignancies, melanoma, and solid tumors requiring stimuli- responsive drug release. However, current evidence remains limited to preclinical studies, with no human trials conducted to date. Challenges related to scalability, long term stability, and regulatory approval continue to hinder clinical translation. Future research should prioritize GMP- compliant manufacturing, clinical validation, and the development of hybrid formulations to fully realize the potential of bilosomes in transforming oncology drug delivery.  

CONTRIBUTION STATEMENT 

Shagufta Shikalgar: original drafting, formal analysis, reviewing.  Natalin Veg: draft, editing and conceptualization. Ashwini Delekar, Shreya Sangale, and Vikas Powar: reviewing and verifying. Sunita Shinde: Final editing and reviewing of main draft.  

DECLARATION OF USING SOFTWARE 

All authors are declared that all the figures are original in nature there are no copyrighting involve, we create images with the help of software named ‘Anara’.

ACKNOWLEDGEMENT

The authors declare that no external funding was received for this work.

CONFLICT OF INTEREST 

All authors have declare that they have no conflict of interest 

FUNDING SOURCE 

None 

ETHICAL APPROVAL 

Not applicable 

REFERENCES

1. Jiang H, Li AM, Ye J. The magic bullet: Niclosamide. Frontiers in oncology. 2022 Nov 21;12:1004978. https://doi.org/10.3389/fonc.2022.1004978 PMid:36479072 PMCid:PMC9720275

2. Thorburn AL. Paul Ehrlich: pioneer of chemotherapy and cure by arsenic (1854-1915). The British journal of venereal diseases. 1983 Dec;59(6):404-5. https://doi.org/10.1136/sti.59.6.404 PMid:6196079 PMCid:PMC1046247

3. Torchilin VP. Drug targeting. European journal of pharmaceutical sciences. 2000 Oct 1;11:S81-91. https://doi.org/10.1016/S0928-0987(00)00166-4 PMid:11033430

4. Kleinstreuer C, Feng Y, Childress E. Drug-targeting methodologies with applications: A review. World Journal of Clinical Cases: WJCC. 2014 Dec 16;2(12):742. https://doi.org/10.12998/wjcc.v2.i12.742 PMid:25516850 PMCid:PMC4266823

5.     Adarsha Ganguly*, Bipasha Pal, Priya Ray, A Thorough Analysis of Targeted Drug Delivery Methods, Int. J. of Pharm. Sci., 2024, 2 (11), 872-877.

6. Ciftci F, Özarslan AC, Kantarci IC, Yelkenci A, Tavukcuoglu O, Ghorbanpour M. Advances in drug targeting, drug delivery, and nanotechnology applications: therapeutic significance in cancer treatment. Pharmaceutics. 2025 Jan 16;17(1):121. https://doi.org/10.3390/pharmaceutics17010121 PMid:39861768 PMCid:PMC11769154

7. Zhuo Y, Zhao YG, Zhang Y. Enhancing drug solubility, bioavailability, and targeted therapeutic applications through magnetic nanoparticles. Molecules. 2024 Oct 13;29(20):4854. https://doi.org/10.3390/molecules29204854 PMid:39459222 PMCid:PMC11510236

8. Md Ikbal Husain, Susmita Sarkar, Nilimanka Das. Bilosomes as Novel Nanocarrier: A Review. Sch Acad J Pharm,2026 Feb 15(2): 32-41. https://doi.org/10.36347/sajp.2026.v15i02.001

9. Kaurav, H.; Tripathi, M.;Kaur, S.D.,et al. Emerging Trends in Bilosomes as Therapeutic DrugDelivery Systems. Pharmaceutics 2024,16, 697. https://doi.org/10.3390/pharmaceutics16060697 PMid:38931820 PMCid:PMC11206586

10. Mitrovi’c, D. etal..A,The Pharmaceutical and Pharmacological Potential Applications of Bilosomes as Nanocarriers for Drug Delivery. Molecules 2025, 30, 1181. https://doi.org/10.3390/molecules30051181 PMid:40076403 PMCid:PMC11901966

11. Pradnya Palekar-Shanbhag, Supriya Lande, et al. Source: Current Drug Therapy, Volume 15, Issue 4, Aug 2020, p. 312-320 https://doi.org/10.2174/1574885514666190917145510

12. Sguizzato, M., Ferrara, F., et al . Bilosomes and Biloparticles for the Delivery of Lipophilic Drugs: A Preliminary Study. Antioxidants, 2023 12(12), https://doi.org/10.3390/antiox12122025 PMid:38136145

13.  Ferlay J, Ervik M, Lam F, et al. Global cancer observatory: cancer today. Lyon: International agency for research on cancer. 2020 Nov 25; 20182020:557-67.

14. Source: Institute for Health Metrics and Evaluation https://share.google/xSgrdCxjxDqtuKvL3.

15. Debabrata Dastidar, Dipanjan Ghosh, Amlan Das,Recent developments in nanocarriers for cancer chemotherapy,OpenNano,Volume 8,2022,100080,ISSN 2352-9520, https://doi.org/10.1016/j.onano.2022.100080

16. Gavas, S., Quazi, S., & Karpiński, T. M. Nanoparticles for Cancer Therapy: Current Progress and Challenges. Nanoscale research letters, 2021 16(1), 173. https://doi.org/10.1186/s11671-021-03628-6 PMid:34866166 PMCid:PMC8645667

17. Saiqa Imtiaz, Umme Tamanna Ferdous, et al. ,Mechanistic study of cancer drug delivery: Current techniques,limitations, and future prospects,European Journal of Medicinal Chemistry, ,2025,117535,ISSN 0223-5234, https://doi.org/10.1016/j.ejmech.2025.117535 PMid:40132495

18. Bukowski K, Kciuk M, Kontek R. Mechanisms of multidrug resistance in cancer chemotherapy. International journal of molecular sciences. 2020 May 2;21(9):3233. https://doi.org/10.3390/ijms21093233 PMid:32370233 PMCid:PMC7247559

19. Garg P, Malhotra J, Kulkarni P, Horne D, Salgia R, Singhal SS. Emerging therapeutic strategies to overcome drug resistance in cancer cells. Cancers. 2024 Jul 7;16(13):2478. https://doi.org/10.3390/cancers16132478 PMid:39001539 PMCid:PMC11240358

20. Hu T, Gong H, Xu J, Huang Y, Wu F, He Z. Nanomedicines for overcoming cancer drug resistance. Pharmaceutics. 2022 Aug 1;14(8):1606. https://doi.org/10.3390/pharmaceutics14081606 PMid:36015232 PMCid:PMC9412887

21. Kharouba M, El-Kamel A, Mehanna R, Thabet E, Heikal L. Pitavastatin-loaded bilosomes for oral treatment of hepatocellular carcinoma: a repurposing approach. Drug delivery. 2022 Dec 31;29(1):2925-44. https://doi.org/10.1080/10717544.2022.2120925 PMid:36081339 PMCid:PMC9467608

22. Abd-Elfadel AA, Ewees MG, Aboud HM, El Rouby WM, et al. Evaluating the efficacy of bilosomes as a promising nanovector for methotrexate against breast cancer. Journal of Drug Delivery Science and Technology. 2025 Aug 11:107395. https://doi.org/10.1016/j.jddst.2025.107395

23. Zarenezhad E, Marzi M, Abdulabbas HT, Jasim SA, Kouhpayeh SA, et al. Bilosomes as nanocarriers for the drug and vaccine delivery against gastrointestinal infections: opportunities and challenges. Journal of functional biomaterials. 2023 Sep 1;14(9):453. https://doi.org/10.3390/jfb14090453 PMid:37754867 PMCid:PMC10531812

24. Fu J, Yu M, Xu W, Yu S. Research progress of bile acids in cancer. Frontiers in oncology. 2022 Jan 20;11:778258. https://doi.org/10.3389/fonc.2021.778258 PMid:35127481 PMCid:PMC8810494

25. Krishnamurthy K, Wang G, Rokhfeld D, Bieberich E. Deoxycholate promotes survival of breast cancer cells by reducing the level of pro-apoptotic ceramide. Breast Cancer Research. 2008 Dec 16;10(6):R106. https://doi.org/10.1186/bcr2211 PMid:19087284 PMCid:PMC2656903

26. Tafazzoli Mehrjardi S, Tafaghodi M, Malek S, Yari D, Mohammadpour AH, Kamali H, Nokhodchi A. Intranasal delivery of cetrorelix via lipid liquid crystal nanoparticles: characterization and pharmacokinetic studies in rats. AAPS PharmSciTech. 2025 Jul 1;26(6):176. https://doi.org/10.1208/s12249-025-03169-6 PMid:40593190

27. Hofmann AF, Mysels KJ. Bile salts as biological surfactants. Colloids and Surfaces. 1987 Jan 1;30(1):145-73. https://doi.org/10.1016/0166-6622(87)80207-X

28. Nguyen TT, Ung TT, Kim NH, Do Jung Y. Role of bile acids in colon carcinogenesis. World journal of clinical cases. 2018 Nov 6;6(13):577. https://doi.org/10.12998/wjcc.v6.i13.577 PMid:30430113 PMCid:PMC6232560

29. Smith DL, Keshavan P, Avissar U, Ahmed K, Zucker SD. Sodium taurocholate inhibits intestinal adenoma formation in APC Min/+ mice, potentially through activation of the farnesoid X receptor. Carcinogenesis. 2010 Jun 1;31(6):1100-9. https://doi.org/10.1093/carcin/bgq050 PMid:20194350 PMCid:PMC2878362

30.  Rainey JB. Bile acids in experimental colorectal cancer. Annals of the Royal College of Surgeons of England. 1986 May;68(3):130.

31. Gándola YB, Fontana C, Bojorge MA, Luschnat TT, Moretton MA, Chiapetta DA, Verstraeten SV, González L. Concentration-dependent effects of sodium cholate and deoxycholate bile salts on breast cancer cells proliferation and survival. Molecular biology reports. 2020 May;47(5):3521-39. https://doi.org/10.1007/s11033-020-05442-2 PMid:32297292

32. Trah J, Arand J, Oh J, Pagerols-Raluy L, Trochimiuk M, Appl B, Heidelbach H, Vincent D, Saleem MA, Reinshagen K, Mühlig AK. Lithocholic bile acid induces apoptosis in human nephroblastoma cells: A non-selective treatment option. Scientific Reports. 2020 Nov 23;10(1):20349. https://doi.org/10.1038/s41598-020-77436-w PMid:33230229 PMCid:PMC7683553

33. Zhang D, Zhu Y, Su Y, Yu M, Xu X, Wang C, Zhang S, Xia L. Taurochenodeoxycholic acid inhibits the proliferation and invasion of gastric cancer and induces its apoptosis. Journal of food biochemistry. 2022 Mar;46(3):e13866. https://doi.org/10.1111/jfbc.13866

34. Youness RA, Al-Mahallawi AM, Mahmoud FH, Atta H, Braoudaki M, Fahmy SA. Oral delivery of psoralidin by mucoadhesive surface-modified bilosomes showed boosted apoptotic and necrotic effects against breast and lung cancer cells. Polymers. 2023 Mar 15;15(6):1464. https://doi.org/10.3390/polym15061464 PMid:36987244 PMCid:PMC10052996

35. Mohsen AM, Wagdi MA, Salama A. Rutin loaded bilosomes for enhancing the oral activity and nephroprotective effects of rutin in potassium dichromate induced acute nephrotoxicity in rats. Scientific Reports. 2024 Oct 11;14(1):23799. https://doi.org/10.1038/s41598-024-73567-6 PMid:39394242 PMCid:PMC11479598

36. Alruwaili NK, Zafar A, Alsaidan OA, Yasir M, Mostafa EM, Alnomasy SF, Rawaf A, Alquraini A, Alomar FA. Development of surface modified bilosomes for the oral delivery of quercetin: Optimization, characterization in-vitro antioxidant, antimicrobial, and cytotoxicity study. Drug Delivery. 2022 Dec 31;29(1):3035-50. https://doi.org/10.1080/10717544.2022.2122634 PMid:36120935 PMCid:PMC9848422

37. Gad S, Awd H, Abdelwahab N, Nasr A, Ghorab M. Bilosomes as a versatile drug delivery system: preparation techniques and biomedical application. Records of Pharmaceutical and Biomedical Sciences. 2024 May 1;8(3):67-86. https://doi.org/10.21608/rpbs.2024.285225.1294

38. Guan P, Lu Y, Qi J, Wu W. Readily restoring freeze-dried probilosomes as potential nanocarriers for enhancing oral delivery of cyclosporine A. Colloids and Surfaces B: Biointerfaces. 2016 Aug 1;144:143-51. https://doi.org/10.1016/j.colsurfb.2016.04.006 PMid:27085046

39. Castelli G, Pelosi E, Testa U. Liver cancer: molecular characterization, clonal evolution and cancer stem cells. Cancers. 2017 Sep 20;9(9):127. https://doi.org/10.3390/cancers9090127 PMid:28930164 PMCid:PMC5615342

40. Tran TH, Tran PT, Truong DH. Lactoferrin and nanotechnology: The potential for cancer treatment. Pharmaceutics. 2023 Apr 28;15(5):1362. https://doi.org/10.3390/pharmaceutics15051362 PMid:37242604 PMCid:PMC10224286

41. Kamel R, Darwish AB, Youness RA, Basha M. Vesicular Nanosystem as a Promising Platform for the Management of Cancer. InCancer Immunotherapy and Nanobiotechnology: An Interdisciplinary Approach 2024 Aug 21 (pp. 759-795). Cham: Springer Nature Switzerland. https://doi.org/10.1007/16833_2024_329

42. Huang Q, Li F, Liu X, Li W, Shi W, Liu FF, O’sullivan B, He Z, Peng Y, Tan AC, Zhou L. Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nature medicine. 2011 Jul;17(7):860-6. https://doi.org/10.1038/nm.2385 PMid:21725296 PMCid:PMC3132290

43. Parashar P, Rana P, Dwivedi M, Saraf SA. Dextrose modified bilosomes for peroral delivery: improved therapeutic potential and stability of silymarin in diethylnitrosamine-induced hepatic carcinoma in rats. Journal of liposome research. 2019 Jul 3;29(3):251-63. https://doi.org/10.1080/08982104.2018.1551408 PMid:30501440

44. Sembiring YE, Effendi WI, Dillon JJ, Soebroto H, Winarno DJ, Puruhito P, Putra IG, Sebayang AN, Negoro SP. Lung cancer: a literature review. Jurnal Respirasi. 2023 Sep 30;9(3):246-51. https://doi.org/10.20473/jr.v9-I.3.2023.246-251

45. Zarenezhad E, Marzi M, Abdulabbas HT, Jasim SA, Kouhpayeh SA, Barbaresi S, Ahmadi S, Ghasemian A. Bilosomes as nanocarriers for the drug and vaccine delivery against gastrointestinal infections: opportunities and challenges. Journal of functional biomaterials. 2023 Sep 1;14(9):453. https://doi.org/10.3390/jfb14090453 PMid:37754867 PMCid:PMC10531812

46. Alhakamy NA, Caruso G, Al-Rabia MW,et al. Piceatannol-loaded bilosome-stabilized zein protein exhibits enhanced cytostatic and apoptotic activities in lung cancer cells. Pharmaceutics. 2021 Apr 29;13(5):638. https://doi.org/10.3390/pharmaceutics13050638 PMid:33947103 PMCid:PMC8146359

47. Hsu SL, Yu CT, Yin SC, Tang MJ, Tien AC, Wu YM, Huang CY. Caspase 3, periodically expressed and activated at G2/M transition, is required for nocodazole-induced mitotic checkpoint. Apoptosis. 2006 May;11(5):765-71. https://doi.org/10.1007/s10495-006-5880-x PMid:16532268

48. Artzy-Schnirman A, Raviv SA, Flikshtain OD, Shklover J, Korin N, Gross A, Mizrahi B, Schroeder A, Sznitman J. Advanced human-relevant in vitro pulmonary platforms for respiratory therapeutics. Advanced drug delivery reviews. 2021 Sep 1;176:113901. https://doi.org/10.1016/j.addr.2021.113901 PMid:34331989 PMCid:PMC7611797

49. Beura PP, Mohapatra SD, Dash A, Satpathy R, Raul SK. Advancement in Green nano-formulation for management of Gynaecological disorders: Emerging trends and Therapeutic insights. Journal of Drug Delivery & Therapeutics. 2026 May 1;16(5):208. https://doi.org/10.22270/jddt.v16i5.7738

50. Kimta N, Majdalawieh MA, Majdalawieh AF. The future of breast cancer treatment: from conventional wisdom to nanotechnology-enabled precision. International journal of molecular sciences. 2026 Feb 24;27(5):2109. https://doi.org/10.3390/ijms27052109 PMid:41828336 PMCid:PMC12984651

51. Abou Assi R, Abdulbaqi IM, Tan SM, Wahab HA, Darwis Y, Chan SY. Breaking barriers: bilosomes gel potentials to pave the way for transdermal breast cancer treatment with tamoxifen. Drug Development and Industrial Pharmacy. 2023 Sep 20:1-2. https://doi.org/10.1080/03639045.2023.2256404 PMid:37722711

52. Zaki RM, Aldosari BN, Alkharashi LA, Alsalhi A, Abo El-Ela FI, Alosaimi RM, Alsunbul M, Afzal O, Said M. Fabrication and appraisal of targeted axitinib loaded bilosomes for the enhanced breast and ovarian anticancer activity. Plos one. 2025 Jul 17;20(7):e0325511. https://doi.org/10.1371/journal.pone.0325511 PMid:40674382 PMCid:PMC12270130

53. Feller L, Khammissa RA, Kramer B, Altini M, Lemmer J. Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face. Head & face medicine. 2016 Feb 5;12(1):11. https://doi.org/10.1186/s13005-016-0106-0 PMid:26850723 PMCid:PMC4744388

54. Waglewska E, Kulbacka J, Bazylinska U. Superior drug delivery performance of multifunctional bilosomes: innovative strategy to kill skin cancer cells for nanomedicine application. International Journal of Nanomedicine. 2024 Dec 31:4701-17. https://doi.org/10.2147/IJN.S450181 PMid:38808148 PMCid:PMC11131132

55. Demartis S, Rassu G, Murgia S, Casula L, Giunchedi P, Gavini E. Improving dermal delivery of rose bengal by deformable lipid nanovesicles for topical treatment of melanoma. Molecular Pharmaceutics. 2021 Sep 23;18(11):4046. https://doi.org/10.1021/acs.molpharmaceut.1c00468 PMid:34554752 PMCid:PMC8564756

56. Papa V, Furci F, Minciullo PL, Casciaro M, Allegra A, Gangemi S. Photodynamic therapy in cancer: Insights into cellular and molecular pathways. Current Issues in Molecular Biology. 2025 Jan 21;47(2):69. https://doi.org/10.3390/cimb47020069 PMid:39996790 PMCid:PMC11854756

57. Din FU, Aman W, Ullah I, Qureshi OS, Mustapha O, Shafique S, Zeb A. Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. International journal of nanomedicine. 2017 Oct 5:7291-309. https://doi.org/10.2147/IJN.S146315 PMid:29042776 PMCid:PMC5634382

58. Peddapalli H, Radha GV, Chinnaiyan SK. Formulation optimization and PK/PD evaluation of novel valsartan bilosomes enhancing transdermal drug delivery. Journal of Drug Delivery Science and Technology. 2024 Feb 1;92:105400. https://doi.org/10.1016/j.jddst.2024.105400

59. Abdullah HD, Kamal I, Sabry SA, Abd Elghany M, El hakim Ramadan A. Effective tailoring of cefepime into bilosomes: a promising nanoplatform for enhancing oral absorption, extending half-life, and evaluating biocompatibility, antibacterial, anti-biofilm, anti-breast cancer activity, ex-vivo, and in-vivo studies. International Journal of Pharmaceutics. 2025 Jan 5;668:125001. https://doi.org/10.1016/j.ijpharm.2024.125001 PMid:39586513

60. Rajput T, Chauhan MK. Bilosome: a bile salt based novel carrier system gaining interest in pharmaceutical research. J Drug Deliv Ther. 2017 Sep 13;7(5):4-16. https://doi.org/10.22270/jddt.v7i5.1479

61.  Thirumalai A, Harini K, Pallavi P, Gowtham P, Girigoswami K, Girigoswami A. Bile salt-mediated surface-engineered bilosome-nanocarriers for delivering therapeutics. Nanomedicine Journal. 2024 Jan 1;11(1):1.

62. Ismail A, Teiama M, Magdy B, Sakran W. Development of a novel bilosomal system for improved oral bioavailability of sertraline hydrochloride: Formulation design, in vitro characterization, and ex vivo and in vivo studies. AAPS pharmscitech. 2022 Jul 8;23(6):188. https://doi.org/10.1208/s12249-022-02339-0 PMid:35799076

63. Foulkes R, Man E, Thind J, Yeung S, Joy A, Hoskins C. The regulation of nanomaterials and nanomedicines for clinical application: current and future perspectives. Biomaterials science. 2020 Aug 25;8(17):4653-64. https://doi.org/10.1039/D0BM00558D PMid:32672255

64. Paradise J. Regulating nanomedicine at the food and drug administration. AMA journal of ethics. 2019 Apr 1;21(4):347-55. https://doi.org/10.1001/amajethics.2019.347 PMid:31012422

65. Sarella PN, Mangam VT. Enhancing nutraceutical bioavailability with bilosomes: A comprehensive review. Asian Journal of Pharmacy and Technology. 2024 Sep 19;14(3):271-80. https://doi.org/10.52711/2231-5713.2024.00044

66. Rodriguez F, Caruana P, De la Fuente N, Espanol P, Gamez M, Balart J, Llurba E, Rovira R, Ruiz R, Martin-Lorente C, Corchero JL. Nano-based approved pharmaceuticals for cancer treatment: present and future challenges. Biomolecules. 2022 Jun 4;12(6):784. https://doi.org/10.3390/biom12060784 PMid:35740909 PMCid:PMC9221343

67. Zafar A, Alruwaili NK, Imam SS, Alsaidan OA, Yasir M, Ghoneim MM, Alshehri S, Anwer MK, Almurshedi AS, Alanazi AS. Development and evaluation of luteolin loaded pegylated bilosome: optimization, in vitro characterization, and cytotoxicity study. Drug delivery. 2021 Jan 1;28(1):2562-73. https://doi.org/10.1080/10717544.2021.2008055 PMid:34866534 PMCid:PMC8654410

68. Zaki I, Abou-Elkhair RA, Abu Almaaty AH, A. Abu Ali O, Fayad E, Ahmed Gaafar AG, Zakaria MY. Design and synthesis of newly synthesized acrylamide derivatives as potential chemotherapeutic agents against MCF-7 breast cancer cell line lodged on PEGylated bilosomal nano-vesicles for improving cytotoxic activity. Pharmaceuticals. 2021 Oct 4;14(10):1021. https://doi.org/10.3390/ph14101021 PMid:34681245 PMCid:PMC8540948

69. Chettupalli AK, Chokkarapu S, Singh A, Babu MR, Singh MP, Bukke SP. Development and fabrication of a novel nano-bilosomal system for enhanced oral delivery of Trametinib: apoptotic induction and anticancer efficacy evaluation. Materials technology. 2025 Dec 31;40(1):2495346. https://doi.org/10.1080/10667857.2025.2495346

70. Abbas H, El-Feky YA, Al-Sawahli MM, El-Deeb NM, El-Nassan HB, Zewail M. Development and optimization of curcumin analog nano-bilosomes using 21.31 full factorial design for anti-tumor profiles improvement in human hepatocellular carcinoma: in-vitro evaluation, in-vivo safety assay. Drug delivery. 2022 Dec 31;29(1):714-27. https://doi.org/10.1080/10717544.2022.2044938 PMid:35243951 PMCid:PMC8903797

71. Nayak D, Rathnanand M, Tippavajhala VK. Unlocking the potential of bilosomes and modified bilosomes: A comprehensive journey into advanced drug delivery trends. AAPS PharmSciTech. 2023 Nov 21;24(8):238 https://doi.org/10.1208/s12249-023-02696-4 PMid:37989979