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Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

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Open Access Full Text Article  Review Article

Introduction about Global infectious disease and use of nanotechnology

Ankita Y. Gawai*, Ravindra L. Bakal , Pooja R. Hatwar , Krushnali N. Nehar, Pranali R. Bhujade

Department of Pharmaceutics, Shri Swami Samarth Institute of Pharmacy, At. Parsodi, Dhamangaon Rly, Dist. Amravati (444709) Maharashtra, India

 

 

Introduction: 

Infectious diseases constitute the primary cause of mortality worldwide¹. Infectious conditions caused by viruses (human immunodeficiency virus (HIV), hepatitis C, and dengue fever, parasites (malaria, trypanosomiasis, and leishmaniasis), and bacteria (tuberculosis and cholera) are significant contributors to morbidity and death in the developing countries². Nanotechnology is a modern and innovative domain characterized by technological advances¹. Nanotechnology is characterized as a technology employed to fabricate nanoscale materials across various domains, including materials engineering, energy, biotechnology, physics, and pharmacy³. It provides an incredible chance for improving drug-resistant microbial infections¹. Furthermore, it significantly influences the treatment of global infections, as well as and health care devices such as imaging probes, drug delivery systems, and diagnostic biosensors within the pharmaceutical sector⁴. Nanoparticles (NPs) are microscopic entities made of several hundred atoms, with dimensions quantified in nanometers⁵. Nanoparticles (NPs) are solid, biocompatible polymeric entities ranging from 1 to 100 nanometers (nm) in size, characterized by an enclosing interfacial coating⁶. Nanoparticles and Nano-pharmaceuticals are classified into many types of nanosystems according to their distinct properties, namely inorganic, organic, lipid-based, polymeric, and nanocapsules, among others⁷.

Organic Nanotechnology - Organic nanoparticles are the most thoroughly researched and widely accepted form of nanoparticles for drug delivery and therapeutic applications in human systems ⁶. Organic nanoparticles contain polymeric nanoparticles, nanocapsules, nanospheres, liposomes, dendrimers, solid lipid nanoparticles, quantum dots, among others⁸.

1. Liposomes - The term liposome is derived from two Greek words: 'Lipo’, meaning fat, and 'Soma,' meaning body. Liposomes are tiny bilayer vesicles created from natural phospholipids. They may contain hydrophilic and lipophilic compounds in aqueous environments or inside the phospholipid bilayer^9.
2. Quantum Dots- Quantum dots, or semiconductor nanocrystals, have unique optical and physical characteristics that render them appropriate for diagnostic advancements¹⁰.
3.  Dendrimers- Derived from the Greek term 'dendron’, signifying tree. Dendrimers are a unique category of polymeric compounds. Dendrimers are often characterized as monodisperse macromolecules exhibiting a highly three-dimensional architecture, which confers a significant degree of surface activity and an extensive range of abilities⁹.

Inorganic nanoparticles: Inorganic Nanoparticles far smaller in size than organic nanoparticles It encompasses size ranges of 1-100 nm with enhanced loading effectivenss⁶. 

It includes:

1. Silver nanoparticles: consist of silver atoms typically measuring between 1 nm and 100 nm. Numerous synthetic techniques have been developed to manufacture AgNP¹. SNPs are notable inorganic nanoparticles with substantial effectiveness, mostly attributed to silver's intrinsic inhibitory and antibacterial properties, as well as its improved conductivity⁶.
2. Gold Nanoparticles - Gold nanoparticles, nanorods, and nanoparticles eliminate bacterial infections by emitting narrowed laser pulses at the appropriate wavelength¹. Gold nanoparticles (AuNPs) possess exceptional qualities, including electrical, optical, mechanical, and biological capabilities, which have garnered substantial interest in the pharmaceutical industry¹¹.
3. Aluminium oxide nanoparticles - The bacterial cell wall became altered at elevated concentrations of aluminium oxide (Al2O3) nanoparticles. Alumina nanoparticles are thermodynamically stable at elevated temperatures¹².

 

 

 
Figure 1: Various classifications of Nanoparticles (NPs) ¹³.

 

 

Infectious Disease –

Coronavirus – 

COVID19, a severe and acute respiratory condition that originated in December 2019 and is a persistent hazard ¹⁴. The initial case was detected in Wuhan, Hubei Province, China, and it swiftly disseminated to 25 nations¹⁵. Corona viruses are classified within the subfamily Coronavirinae, Order Nidovirales, including family Coronaviridae¹⁶. 

The origin of this name comes from the Latin term corona, or crown¹⁷. 

Coronaviruses (CoVs) have been among the primary causes of death in recent decades¹⁸. Coronaviruses are single stranded, Positive sense RNA viruses that possess the longest genome of any known RNA virus, with a genomic content (GC) varying from 32 to 43%¹⁷.

Recent research from China indicates that COVID19, the illness produced by SARSCoV2, is characterized bythree clinical patterns: asymptomatic or mildly symptomatic cases, mild to moderate disease, and severe pneumonia necessitating ICU hospitalization¹⁹.

The illness is spread by respiratory droplets from infected individuals during coughing or sneezing and mostly impacts the lung parenchyma¹⁵.

Categories of coronavirus ²⁰.

• Alpha coronavirus
• Beta coronavirus
• Gamma coronavirus
• Delta coronavirus

 

 

Figure 2: Structure of the human coronavirus²¹.

 

 

Symptoms of coronavirus

The predominant symptoms of COVID19 are fever (85.6%), cough (68.7%) and tiredness (39.4%). Dyspnea, headache, anorexia, anosmia, ageusia, tachypnea, emesis, diarrhea, rhinorrhea, and abdominal discomfort are less prevalent symptoms of the disease²². Conversely, sputum production (33.4%), respiratory distress (18.6%), pharyngodynia (13.9%), chills (11.4%), nasal obstruction (4.8%), and hemoptysis (0.9%) constitute the principle symptoms of this condition¹⁵.

Nanotechnology Utilized in COVID-19 
The utilization of nanotechnology in personal protective equipment (PPE) imbedded textiles, which enhance the physicochemical features of fabrics, including fire resistance, self-cleaning capabilities, antimicrobial effects, and UV protection, among others²³. Nanomedicine strategies primarily aim to mitigate toxicity and adverse effects while addressing constraints associated with therapeutic agents²⁴.

Nanotechnology in SARS-CoV-2 Detection

The initial diagnostic stage for COVID-19 patients relies on their travel and communication history²⁵. Nucleic acid-based testing was initially the principal detection method for SARS-CoV-2. Combinatorial Nanotechnology-Driven Therapy²⁶. Protein assays with nanotechnology. Nanotechnology-based point-of-care testing (POCT) can be employed to identify illnesses in remote locations and deliver immediate treatment, hence aiding in the prevention of infection transmission²⁷.

Application of nanotechnology in coronavirus therapy 

Nanotechnology may enhance the safety and efficacy of COVID-19 treatments by facilitating drug encapsulation, targeted delivery to areas, and minimizing drug toxicity²⁸.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 1: Advantages of Nanotechnology in COVID-19¹.

	Conventional Approach	Nanotechnology-based Approach
Diagnosis	Lengthy time of detection Limitations in antibody tests like technical production and identification problems Lack of suitability False positive or negative findings	Early-stage detection No or minimized contamination Protected error risk Sensitivity Possibility of miniaturization with metallic NPs NPs conjugated with corona virus specific antibodies
Treatment	Absence of effective therapeutics Low surface area to mass ratio Chemical reactivity/instability Side effects from high serum and non-target Concentrations Inaccessibility of the target by the drug	Stabilized in the systemic circulation Targeted, controlled and sustained delivery Controllable size and size-dependent transport, biocompatibility Reduced toxicity Theranostic approach Noninvasive administration like inhalations
Vaccines	Low blood stability, slow absorption and short half life Insufficient immune response Higher doses risk for side effects Poor immunogenicity, Absorption non targeting, slow absorption High storage and delivery requirements	Multiple targeting Strong immuno stimulatory effects Manageable size and surface properties Reduced adverse effects Controllable drug release Strong stimulation of humoral and cellular responses
Personal prospective equipment (PPE)	Shortage of supplies Low filtration efficiency Single-use (use-and-throw) - economic, eco-safety and waste management problems Breathing pressure and heat dissipation Ineffective disinfection and sanitizing	Reusable and improved bio-safety Self-cleaning, high efficiency and effective disinfectants with antimicrobial and antiviral properties Designing contamination-free equipment Adding inherent virucidity to surfaces Antimicrobial releasing self-sanitizing and surface topolo- gies with viral self-deactivation

 

 

MALARIA: 

In 2020, there were an expected 241 million cases and 627 thousand fatalities due to malaria globally ²⁹. Malaria is a protozoan illness carried by female Anopheles mosquitoes, caused by the infection of a susceptible host with Plasmodium parasites³⁰. The name malaria originates from the Italian phrase “malaaria,” which translates to bad air³². The bulk of illnesses are attributed to P. falciparum and P. vivax, with the more severe P. falciparum responsible for the bulk of malaria-related fatalities worldwide³².

Human Plasmodium species responsible for malaria³³:

b) Plasmodium vivax

c) Plasmodium ovale

d)Plasmodium knowlesi

e) Plasmodium malariae 

Signs and Symptoms of Malaria- The prevalent symptoms encompass fever, chills, headache, myalgia, emesis, severe anemia, spleen unresponsive coma, and mortality if untreated³⁴. Malaria is the predominant etiology of fever, and the majority of patients exhibit few aberrant physical signs².

In uncomplicated malaria, symptoms advance sequentially through the chilly, heat, and sweating phases.

• A feeling of cold combined with shivering

• Fever, headaches, and vomiting 

• Seizures may occasionally manifest in younger individuals afflicted with the condition.

• Sweating, succeeded by a reversion to baseline temperature, accompanied with fatigue³⁵.

 

 
Figure 3: Life Cycle of the Malaria Parasite³⁴.

 

 

Techniques employed in the laboratory diagnosis of malaria encompass

1. Microscopic Diagnosis.
2. Antigen Detection Technique 
3. Molecular Detection Technique (PCR). 
4. Serological Detection Method (ELISA)
5. Field Assessment 
6. Diagnostic procedures in the laboratory³⁵
7. Rapid diagnostic assays or immunochromatographic testing - This device is recognized as a prevalent point-of-care test (POCT) for malaria diagnosis. Rapid diagnostic tests (RDTs) utilize a lateral flow immunoassay method to identify biomarkers unique to the Plasmodium parasite³⁶.

Application of nanotechnology in malaria therapy – 

• Metallic nanoparticles - gold and silver

1. Nonbiological techniques (physical and chemical).
2. Biological Method (sustainable nanoparticles from bacteria, fungi, and plants)

• Inorganic non-metallic nanoparticles: Titanium dioxide.

1. Zinc oxide 
2. Cadmium oxide³⁶

• Carbon-based nanoparticles: Multiwalled carbon nanotubes. 

Liposomes may transport both hydrophilic and hydrophobic medicines, exhibit great stability, are biodegradable, non-toxic, and can be delivered via parenteral and cutaneous routes. They boost the therapeutic index and allow for surface functionalization possibilities⁴⁴.

Nanoemulsions may be administered by oral, parenteral, and cutaneous routes, are thermodynamically stable, and can be sterilized using filtering^.

Metallic nanoparticles have antifungal and antibacterial properties, characterized by excellent stability and uniformity in structure³⁴.

 Nanostructured lipid carriers (NLCs) have enhanced stability and drug loading relative to solid lipid nanoparticles (SLNs), possess an extended shelf life, and facilitate straightforward scaling and sterilization. Polymeric nanoparticles are biocompatible, cost-effective, circumvent the reticular endothelial system, allow for ligand-specific interactions, and prevent drug leakage.

Solid lipid nanoparticles are biocompatible, easily scalable and sterilizable, very stable, and may be delivered by oral, parenteral, and cutaneous routes. They eliminate the need of organic solvents and can encapsulate both lipophilic and hydrophobic medicines⁶.

TUBERCULOSIS – 

Tuberculosis (TB) is an airborne infectious illness caused by Mycobacterium tuberculosis (MTB) that predominantly impacts the lungs³⁷. Prior to the COVID-19 epidemic, more than 4,000 individuals died to tuberculosis (TB) regularly³⁸ 

Characteristics of Mycobacterium tuberculosis: Mycobacterium tuberculosis is classified as 

ORDER- Actinomycetes, 

CLASS- Actinomycetes

FAMILY- Mycobacteriaceae. 

GENUS- Mycobacterium³⁹

Mycobacterium tuberculosis is an aerobic, non-spore-forming, nonmotile facultative bacterium characterized by curved intracellular rods. 

Dimensions - 0.2-0.5 micrometers by 2-4 micrometers. 

The cell walls of mycobacteria include mycolic acid-rich long-chain glycolipids and phospholipoglycans (mycolides), which safeguard them from lysosomal degradation and preserve red basic fuchsin dye upon acid rinsing, characteristic of the acid-fast stain^39,40.

Symptoms of tuberculosis ⁴¹: Include the expectoration of mucus and sputum.

1. Fever - 74 (46.5%)
2. Weight reduction - 82 (51.6%)
3. Thoracic discomfort,
4. Jaundice: 31 cases (20.0%)
5. Diarrhea 
6. Hemoptysis
7. Nocturnal hyperhidrosis

Types of tuberculosis – There are primarily two forms of TB.

1. Active TB - Bacteria reproduce and spread inside the body, resulting in tissue destruction.
2. Latent tuberculosis - This stage can last for an extended duration. Treatment typically involves administering a single medication for a duration of nine months. In active tuberculosis, germs proliferate and disseminate throughout the body, resulting in tissue damage⁴².

Nanotechnology employed in the detection and treatment of TB – 

Various nanoparticles, such as metallic nanoparticles (gold and silver) and fluorescent nanoparticles, can be utilized for diagnosing numerous infectious illnesses, including tuberculosis. Gold nanoparticles were the first nanomaterials employed as nano-diagnostics for tuberculosis testing in 1996⁴³.

Quantum Dots – 

Nanotechnology employs semiconductor nanocrystals, known as "quantum dots," measuring no more than 10 nanometers, which may be induced to glow in various colors based on their size, to enhance the specificity of fluorescence or electron microscopy in detecting TB bacilli⁴⁴.

Imaging Nanotechnology – 

Labeling of targeted TB-bacilli molecules with quantum dots or synthetic chromophores, such as fluorescent proteins, to enable direct examination of intracellular signalling complexes through optical techniques, such as confocal fluorescence microscopy or correlation imaging⁴⁴.

Sparse Cell Detection - This technique leverages the distinctive characteristics of sparse cells, seen in the variations in deformation of intracellular TB bacilli.

The nanotechnology-based drug delivery system enhances the tolerance of harmful chemotherapies, facilitates prolonged and regulated drug release, and ultimately increases bioavailability⁴².

Exosomes are lipid bilayer membrane vesicles with a diameter ranging from 30 nm to 150 nm, released by nearly all live cells, and have a varied function in the detection and treatment of TB infection.

Liposomes: Rifampicin encapsulated in liposome nanoparticles has demonstrated enhanced anti-TB efficacy, increased absorption rate, reduced cytotoxicity, improved in vivo drug administration, and prolonged retention duration.

Noisome: Niosomes as a drug carrier, may be employed for prolonged medication delivery to minimize drug consumption and side effects by enhancing bioavailability⁴⁵.

 

 
Figure 4: Nanocarrier-based anti-tuberculosis medication delivery system⁴⁶.

 

 

STD: SEXUALLY TRANSMITTED DISEASE: 

Sexually transmitted infections (STIs) result in reproductive morbidity globally. In 2019, the World Health Organization (WHO) anticipated 376 million new cases of chlamydia, gonorrhea, syphilis, and trichomoniasis⁴⁷. Sexually transmitted infections (STIs) are among the most prevalent communicable illnesses globally, linked to considerable morbidity and mortality, with a rising frequency worldwide⁴⁸.

 STIs are responsible for HIV and other illnesses⁴⁹.

 HIV/AIDS represents a significant challenge for the medical community, as AIDS is life-threatening and still lacks a cure, although it may be managed. The human immunodeficiency virus (HIV) is a retrovirus classified under the lentivirus family. HIV comprises a cylindrical core encased in a spherical lipid bilayer exterior.

HIV is spread through three primary methods. Sexual intercourse, exposure to contaminated bodily fluids, including sweat, tears, saliva, semen, and vaginal secretions. Vertical transfer from mother to kid during gestation, parturition, or lactation⁵⁰.

There are two strains of HIV that lead to AIDS, namely

HIV-1 
 HIV-2
 Acute HIV infection often starts with symptoms resembling mononucleosis.

Symptoms of HIV seroconversion may encompass fever, chills, lymphadenopathy, stomach discomfort, pharyngitis, diarrhea, and rash.

Incubation duration: 2-6 weeks⁵¹.

There are four primary phases of HIV⁵⁰_.

Stage I: Clinical Latency/Asymptomatic Disease 

Stage II: Mild Signs and Symptoms of HIV

Stage III: Advanced manifestations and indicators of HIV 

Stage IV: Acquired immunodeficiency syndrome (AIDS).

AIDS: The human immunodeficiency virus (HIV), the etiological agent of acquired immune deficiency syndrome (AIDS), was identified more than 25 years ago. Acquired Immunodeficiency Syndrome (AIDS) is characterized by a CD4+ T cell count below 200 cells per µL or the manifestation of certain disorders in conjunction with an HIV infection⁴⁹.

Diagnosis of AIDS

1)ELISA assay, 

2)Saliva test. 

3)Viral load test ⁴⁵. 

Nanotechnology applied in HIV treatment has led to the introduction of various nanoparticle formulations aimed at prolonging the therapeutic window, thereby decreasing the required dosing frequency and addressing patient compliance issues. Stavudine, a nucleoside analogue, has been encapsulated in gelatin nanoparticles and subsequently coated with a layer of soya lecithin-liposome for dual-functionalized HIV-1 treatment.

Virucidal nanomaterials- Various nanomaterials, including metal nanoparticles and graphene-based nanosheets, have inherent virucidal capabilities attributable to their distinctive physicochemical characteristics.

An unconventional nanoparticle platform consisting of endogenous ribonucleoprotein, known as vaults, has been utilized for HIV-1 therapy. The distinctive characteristics of nanoparticles are especially appealing for addressing several obstacles that hinder the effective practical use of RNAi antiviral treatment. Diverse tissue-targeted nanoparticle formulations, including those for vaginal administration, topical use, and cerebral distribution for neurosis treatment, have been synthesized to enhance the management and prevention of HIV infections at specific tissue locations⁵³.

 

 

Figure 5: Antiretroviral drug-conjugated vault nanoparticles for the inhibition of human immunodeficiency virus (HIV)⁵³.

 

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