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Review Article | DOI: https://doi.org/10.31579/2639-4162/217
Department of Pharmaceutics, RBVRR Women’s college of Pharmacy.
*Corresponding Author: Abbaraju Krishna Sailaja, Department of Pharmaceutics, RBVRR Women’s college of pharmacy
Citation: Abbaraju K. Sailaja, Shreya Deshmukh, (2024), Applications of Nanoparticles in Drug Targeting, J. General Medicine and Clinical Practice, 7(15); DOI:10.31579/2639-4162/217
Copyright: © 2024, Abbaraju Krishna Sailaja. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 12 August 2024 | Accepted: 31 August 2024 | Published: 06 September 2024
Keywords: blood transfusions; hiv; immune function; anemia; quality of life
The current article sites the importance of the emerging and promising future of new dosage form, nanoparticles, and the importance of nanoparticles in various diseases. It is now possible to determine the fate of Medicine entering the body with the use of advanced drug targeting technologies. Nanotechnology is expected to revolutionise manufacturing and have a huge impact on life sciences, particularly in the area of delivery, diagnostics, nutraceuticals, and biomaterials synthesis.In this article the various applications of nanopartcle drug delivery system is discussed in detail.
1.Passive Targeting
The preferential accumulation. Of chemotherapeutic drugs in solid tumours is the most well-known example of passive targeting when compared to healthy tissue. These results in increased vascular permeability in tumour tissues. Because ligand receptor interactions in passive targeting can be highly selective, Accurate targeting at the place of interest is achievable. Mucosal obstacles, nonspecific particle absorption, and nonspecific medication delivery are among them (as a result of uncontrolled release)1.
2.Active Targeting
Drug Delivery Approach in Skin Diseases
Skin diseases are follicular and cutaneous. Nanoparticle delivery for cutaneous disease treatment is preferred, with minor side effects [1]. The conventionally used creams, gels, and ointments are insufficient for delivering drugs due to low penetration in skin tissues. The polymeric micelles enhance drug penetration into the skin tissue to treat skin cancer. [2] Gold nanoparticles are extremely small in size and can penetrate easily and effectively with very low toxicity and no skin damage. As such, they are used widely in formulations for skin diseases.
Drug Delivery Approach in Bone Diseases
Bone diseases include bone defects due to many pathological factors, such as fracture, trauma, osteoporosis, arthritis, infections, and many other diseases. ³ In, bone regeneration as a disease treatment is a very complex process, due to which nanomaterials and biological materials are fused to repair bones effectively. The combination of biomaterial and nanomaterial has reduced bone implantation through the development of bone bio scaffolds.
Drug Delivery Approach in Heart Diseases
Cardiovascular diseases include myocardial infraction (MI)ischemic impairment, coronary artery disease (CAD), heart arrhythmias, pericardial disease, cardiomyopathy (heart muscle disease), and congenital heart disease. All these illnesses are the basic main cause of mortality and morbidity in the world. Cardiac diseases in humans involve in the morphogenesis of heart arrangement, functionality, and the healing and periodic shrinkage of cardiac muscles. Modern therapeutic approaches are developed to stop heart failure after myocardial infarction. Liposomes, silica NPs, dendrimers, cerium oxide NPs, micelles, TiO2 NPs, stents with nano-coatings, microbubbles, and polymer–drug conjugates are used for drug delivery. Magnetic nanoparticles like magneto liposomes (MLs) are made up of the union of liposomes and magnetic nanoparticles. They are used as magnetic-targeted drug delivery.The PEGylation of MLs increases their rate of flow in the blood, and pairing of the MLs with antibodies raises the rate of active target to pretentious positions. Namdari and his co-workers performed experiments in a mice model afflicted with myocardial infraction (MI). Liposomes are used with various modifications and in different ways; they are adapted to load drugs on NPs for efficient delivery inside the cell. Cationic liposomes, perfluorocarbon nanoparticles, polyelectrolyte nanoparticles, and polymeric nanoparticles are the forms of nanocarriers [2,3].
Cancer Therapy: Nanoparticles can be designed to target tumor cells specifically, reducing damage to healthy tissues. For example, nanoparticles can be coated with ligands that bind to receptors overexpressed on cancer cells, ensuring the drug is delivered directly to the tumor site.
Brain Targeting: Nanoparticles can cross the blood-brain barrier (BBB), which is a significant challenge in treating neurological diseases. This capability is essential for delivering drugs to treat conditions like Alzheimer's, Parkinson's, and brain tumors[4,5].
Controlled and Sustained Release
Prolonged Drug Release: Nanoparticles can be engineered to release drugs over an extended period, reducing the frequency of dosing and improving patient compliance. Polymers like PLGA (poly (lactic-co-glycolic acid)) are often used for this purpose.
pH-Responsive Systems: Nanoparticles can be designed to release their drug cargo in response to the pH of the surrounding environment, such as the acidic conditions in tumors or inflamed tissues [6,7].
Improved Solubility and Stability
Solubility Enhancement: Many drugs have poor water solubility, limiting their bioavailability. Nanoparticles can enhance the solubility of these drugs, making them more effective.
Stabilization of Labile Drugs: Nanoparticles can protect drugs that are sensitive to degradation by enzymes or harsh environmental conditions, ensuring they reach their target in an active form [9,10].
Vaccination
Vaccine Delivery: Nanoparticles can enhance the immune response by serving as adjuvants or by delivering antigens to specific immune cells. This approach is being explored for vaccines against various infectious diseases, including COVID-19.
Gene Delivery
Gene Therapy: Nanoparticles can deliver genetic material (like DNA, RNA, or siRNA) into cells, a crucial aspect of gene therapy for treating genetic disorders. Lipid nanoparticles, for example, are used to deliver mRNA in some COVID-19 vaccines.
Diagnostics and Theranostics
Imaging and Therapy Combination (Theranostics): Nanoparticles can be designed for both imaging and treatment, allowing for real-time monitoring of therapeutic outcomes. For example, nanoparticles can be loaded with a drug and a contrast agent for MRI, enabling simultaneous treatment and tracking of disease progression11,12.
Overcoming Multidrug Resistance
Efflux Pump Inhibition: Some nanoparticles can inhibit efflux pumps, which are responsible for drug resistance in cancer cells, allowing chemotherapeutic agents to remain effective.
Nanoparticles offer a versatile and effective platform for improving drug delivery, potentially transforming the treatment of various diseases by enhancing efficacy, reducing side effects, and improving patient outcomes13.
Tumour targeting using nanoparticulate delivery systems:
The argument for employing nanoparticles for tumor targeting is based on the fact that one of the nanoparticles most efficient functions is delivering medicine to tumor targets via improved permeability and retention. This can also be accomplished by using ligands on the surface of nanoparticles to actively target them. Nanoparticles decrease drug exposure to healthy tissues by limiting drug distribution to the target organ. The liver, spleen, lungs of mice treated with doxorubicin-based polyps. Poly (isohexilecyanoacrylate) nanospheres had higher doxorubicin concentration that mice treated with free doxorubicin. It was also shown that the polymeric composition of nanoparticles such as polymeric biodegradation profile and the associated drug’s Molecular weight, polymer type, localization in Nanospheres. And mode of incorporation technique, adsorption or incorporation, hydrophobicity, all have a significant impact on drug distribution patterns in vivo Furthermore, nanoparticles have the benefit of forming nanoparticles quickly, within one. By two to three hours, and this is likely due to MPS and endocytosis or phagocytosis process. A previous study in tumour bearing my short the biodistribution and pharmacokinetics pattern of a cyclic RGB Doxorubicin nanoparticle formulation. Drug concentrations in the heart lung, kidney, and plasma decreased overtime in this biodistribution investigation, while drug accumulation was discovered in the liver spleen, and tumour at 48 hours after injection, the liver received the Highest percentage of the injected dose, 56% while the tumour. Received only 1.6 percent. This research shows that nanoparticles have a high likelihood of being caught by the liver. The most difficult aspect of employing nanoparticles for tumour targeting, according to this and other studies, is avoiding particle uptake by the mononuclear phagocytic system. Mps in the liver and spleen. The ability of the mononuclear phagocytic system to endocytosis or phagocytosis nanoparticles provides a way to deliver therapeutic drugs to these cells effectively. This biodistribution may be useful in the treatment of mononuclear phagocytic system, rich organs or tissues with localized tumours [14,15].
Previous study, using Doxorubicin in loaded conventional nanoparticles to treat a hepatic metastasis model in mice proof to be beneficial. Furthermore, it was revealed that when the free medicine was taken, there was a higher reduction in the degree of metastasis. This is due to the drug reservoir been allocated. To malignant tissues and Doxorubicin been transferred from healthy tissue, resulting in improved therapeutic efficacy of the formulation. Several other factors, such as tissue histology, assure a significant concentration of nanoparticles in Kupffer cells, lysosomal vesicles, whereas nanoparticles could not be clearly recognized in tumoral cells. When typically, nanoparticles are used in chemotherapy, damage against. Kupffer cells is likely to occur to some level, resulting in Kupffer cell deficit. This could lead to a reduction in hepatic uptake and reduction in therapeutic efficacy. Furthermore, bone marrow can be a good target for conventional nanoparticles. The location of action for most anti-cancer medications is the bone marrow, which is significant, yet unfavourable because therapy with chemotherapeutic agents at this site increases myelosuppressive effects. As a result, the ability of unconventional nanoparticles to boost anti-cancer treatment efficacies restricted to tumours targeted at the level of organs within mononuclear phagocytic system. Furthermore, if nanoparticles are rapidly cleared after intravenous administration, targeting anti-cancer drug loaded nanoparticles to other tumour locations is impossible [16,17].
Nanoparticles for oral drugdelivery of peptides and proteins:
Search for additional antigenic compounds in the fields of biotechnology and biochemistry is helping to keep vaccine production going. Various bio macromolecules and vaccines are being investigated as a result of recent advancements in biotechnology. As a result, an appropriate carrier system is urgently needed, which remains a challenge due to the fact that viability of these compounds is limited by gastrointestinal epithelial barriers and their sensitivity to gastrointestinal breakdown by digestive enzymes. Insulin loaded polymeric nanoparticles preserved insulin activity and reduced blood glucose in diabetic rats for up to 14 days after oral administration Demonstrating that polymer-based nanoparticles can help encapsulate bio active molecules and protect them from enzymatic and hydrolytic degradation.The surface area of human mucosa is 200 times that of skin, according to popular belief. Physiological and anatomical impediments to protein or peptide-based medication delivery have been encountered18.
The intestinal mucosa’s histological features are designed to effectively inhibit the intake of particulate particles from the environment. To get the through the gastrointestinal barrier. A drug can be administered in a colloidal carrier system, which could improve the drug delivery systems interactions with the epithelial cells in the gi tract. The use of ligands product nanoparticles to epithelial cells could improve the interaction of nanoparticles with adsorptive enterocytes mediated by selective binding to particulate receptors and M cells of pier patches in the Gi tract. Targeting can be divided into two types, those that use selective binding to ligands or receptors, and those that use a nonspecific adsorptive mechanism enterocytes surface may act as binding sites for colloidal drug carriers containing suitable ligands Since M cells Express cell specific carbohydrates. A particular receptor mediated mechanism efficiently binds many glycoproteins and lectins to this type of surface structure. Oral peptide adsorption has been examined using lectins like tomato, lectin and bean lectin. Selective mucoprotein, which is generated by the mucus membrane in the stomach and bind selectively to Cobalamin, is necessary to make the process more efficient. Mucoprotein resorption in the ileum is mediated by selective binding to particular receptors, which can improve absorption even further. Nonspecific interactions can also help increase absorption. In general, macromolecules and particulate materials are absorbed in the gastrointestinal system via the paracellular or endocytotic pathways. For the paracellular route of absorption of nanoparticles containing polymeric materials such as starch or chitosan, less than 1% of mucosal surface area is used. The permeability of macromolecules paracellularly is improved by such polymers. Endocytotic absorption of nanoparticles can be accomplished through receptor mediated endocytosis (active targeting) or adsorptive endocytosis, which does not require any ligands. This entire process is aided by the presence of electrostatic forces (hydrogen bonding or hydrophobic bonding) between the cell surface and the absorbed substance. Adsorptive endocytosis is primarily influenced by the size and surface properties of the materials; for example, positive surface charged nanoparticles with a hydrophobic surface provide an affinity to adsorptive enterocytes, whereas negative surface charged nanoparticles with a hydrophilic surface have a greater affinity to adsorptive enterocytes and M cells. As a result, it has been determined that size, in surface charge, and hydrophilicity all play a significant impact in material absorption [19].
Nanoparticles For Gene Delivery
Several vaccine-based nanomedicines work by delivering genes to host cells and demonstrating their expression through antigenic protein synthesis to trigger an immune response. One of the most recent polynucleotide vaccines works by transferring genes encoding relevant antigens to host cells (where they are expressed), causing the antigenic protein to be produced in the proximity of professional antigen presenting cells, triggering an immune response. Since intracellular protein synthesis, rather than extracellular deposition, stimulates both arms of the immune system, such vaccines are responsible for both humoral and cell-mediated protection. Polynucleotide vaccines are made up of a core ingredient called DNA, which can be generated cheaply and had far superior storage and handling capabilities than the majority of protein-based vaccines’ constituents. Many traditional vaccines are expected to be replace by polynucleotide vaccines due to their potential immunotherapy. However, there are a number of difficulties with this polynucleotide-based vaccination that limit its use. These difficulties include ensuring that the polynucleotide’s integrity is preserved during delivery to the target cell population and its localization to the nucleus of these cells, as well as ensuring that the polynucleotide’s integrity is maintained during deliver plasmid DNA based nanoparticulate systems serve as a potential sustained release gene delivery strategy due to their quick escape from the degradative endo-lysosomal compartment to the cytoplasmic compartment. Previous research has demonstrated that these nanoparticles intracellular absorption and end lysosomal escape provide continuous DNA release, resulting in sustained gene expression. PLGA nanoparticles harbouring therapeutic genes such bone morphogenic protein could be used in this technique to aid bone repair to the target site is still in regard [20].
Nanoparticles For Drug Delivery in The Brain
The nervous system is one of the body’s most fragile micro-environments, with the blood- brain barrier (BBB) managing its homeostasis and protecting it. The most critical problem restricting the development of novel medications for the central nervous system is the blood- brain barrier (BBB). The blood-brain-barrier (BBB) is a complex system that tightly controls the transport of ions from a small number o small molecules and an even smaller number of macro molecules from the bloodstream to the brain, protecting it from accidents and diseases. Endothelial cells with tight connections, enzymatic activity, and active efflux transport mechanisms make up the BBB, which is relatively impenetrable. It efficiently blocks the flow of water-soluble molecules from the blood circulation into the CNS and, through the action of enzymes or efflux pumps, can also diminish the concentration of lipid-soluble molecules in the brain. Because the BBB only allows selective transport of molecules that are required for brain function, it also prevents the delivery of medications to the brain, inhibiting the treatment of a variety of neurological illnesses. The ability of poly (butyl cyanoacrylate) based nanoparticles to carry dalargin, hexapeptide, doxorubicin, and other medicine into the brain has been revealed, which is noteworthy given how difficult it is for pharmaceuticals to penetrate the BBB. Despite multiple papers claiming effectiveness with polysorbate coated NPs, this method has a number of flaws, including rapid NP disintegration, toxicity induced by high polysorbate concentrations, and desorption of the polysorbate coating. In addition to certain publications, anti-transferrin receptor MAbs (anti-transferrin receptor MAbs), the most researched BBB targeting antibody neurodegeneration (e.g., amyotrophic lateral sclerosis, Alzheimer’s, Parkinson's, Huntington disease, and Prion disease), genetic deficiencies (e.g., Lysosomal storage disease, leukodystrophy), and genetic deficiencies (e.g., lysosomal storage diseases, leukodystrophy), and genetic deficiencies (e.g., lysosomal storage diseases, leukocyte and several types of cancers. Even if candidate medications for the treatment of such diseases exist in concepts, they are now unavailable due to insufficient access to the central nervous system (CNS) due to the presence of the blood-brain barrier (BBB), which prevents blood from reaching the brain. It’s feasible that these BBB specific compounds will soon be employed to target nanoparticles to the brain
Anthray Vaccine Uses Nanoparticles to Produce Immunity
Bacillus anthracis, a Gram-positive spore-forming bacteria, causes anthrax. B anthracis toxins are primarily caused by an AB type toxin compared of the receptor-binding subunit protective antigen (PA) and two enzymatic sub-units knows as fatal factor and edoema factor. Antibodies against PA, the core components of the current anthrax vaccine, confer protective immunity against B. anthracis infection. In the August issue of infection and immunity, university of Michigan Medical School scientists report that a vaccination against anthrax that is more effective and easier to give than the current vaccine has shown highly effective in tests in mice and guinea pigs. The vaccinations are safe and effective, although it does require numerous shorts and annual boosters. By treating the inside of the animals’ noses with a “nano emulsion,” a suspension of water, soybean oil, alcohol, and surfactant emulsified to generate droplets as small as 200-300nm, the researchers were able to elicit a critical anthrax protein through the nasal membranes, allowing immune system cells to react to the protein and trigger an immunological response. This prepares the immune system to fight infection as soon as it comes into contact with the entire germ. To equal the breadth of a human hair,265 drops would have to be lined up side by side. In regions where refrigeration is not available, it is simple to keep and utilise. An effective and simple-to-use vaccination would be a useful weapon for health officials coping with any future incident in which anthrax bacteria are dispersed by a terrorist. If a nasal nano emulsion-based anthrax vaccine proves effective in humans, the researchers believe it might be administered to patients even after they have been exposed to anthrax, coupled with antibiotics. Vaccines gives after exposure are used to speed up the immune response in some disease [21].
Stem Cell Therapy
Nanotechnology has the potential to improve stem cell therapy. Nanoparticles are important participants in disclosing the fate and performance of stem cell therapy because of their synergy between size, structure, and physical properties. In stem cell research and therapy. Nanoparticles clearly have a lot to offer. Stem cell therapies have a lot of promise for treating a variety of diseases and disorders. With so many stem cell replacement therapies in clinical trials right now, there is a big push to figure out what makes them work. And one of the most important ways is to follow stem cell migration proliferation and differentiation in vivo. Tracking systems should ideally be non-invasive, high resolution and allow tracking in three dimensions to be most useful. Magnetic resonance imaging is one of the best approaches, but it requires a contrast agent to be put into the cells to be followed. And magnetic nano particles are one of the most often used in stem cell tracking. Researchers were able to boost stem cell potential by using nano particles to stimulate the repair of injured vascular tissue and prevent muscle degeneration. Furthermore, researchers are looking into the significance of stem cells in stimulating immune system and new blood vessels formulation after they were implanted into a living organism. This was studied. Cells may not be able to renew tissue well enough to keep it alive for an extended period of time. As a result, cells can profit from the assistance of performance enhancing genes that drive tissue growth. Typically. Researchers are viral vectors to deliver therapeutic genes to stem cells. Tiny nanoparticles may be twice as likely to seek to the interface of two non-mixing liquids than previously thought according to dynein nano particles, can be used for delivering this therapeutic gene. This study paves the path of for nanoparticles to be used in living cells, polymer composites and high-tech foams, gels and paints [22].
Gold nanoparticles detect cancer:
Due to ability to adjust the size shape structure composition assembly. Encapsulation and tuneable optical properties of metallic nanostructures. They are more flexible particles than other nano materials. Among that metallic nanostructures that can be used aunts appear to be in particular interest in medical field, demonstrating high efficacy in cancer therapy. The constant. Fascination with aunts stems for their tuneable optical properties, which may be regulated and modified for disease therapy and diagnosis. Gold nanoparticles have been used as Ultra-sensitive fluorescent strokes to detect cancer, biomarkers in human blood by a number of studies. This method, high sensitivity, outperforms conventional approaches by several orders of magnitude, making it more suitable for direct detection of viral log bacterial DNA. These Nano particles are intriguing biological probes because they are simple to make and unlike other fluorescent probes. Do not heat up and burnout after prolonged light exposure. Researchers from China use the particles to identify Carcinoma embryonic antigen and alpha foetal protein to essential biomarkers in the detection of diseases such as liver breast and lung cancer, according to one study. They used nanoparticles conjugated with antibodies to detect amount of biomarker levels in the sample in the study [23