Drug Delivery System PDF

Drug delivery system  Nanotechnology is the study of extremely tiny things and is basically the hub of all science disciplines including physics, chemistry, biology, engineering, information technology, electronics, and material science. The structures measured with nanotechnology range f...

Drug delivery system  Nanotechnology is the study of extremely tiny things and is basically the hub of all science disciplines including physics, chemistry, biology, engineering, information technology, electronics, and material science. The structures measured with nanotechnology range from 1–100 nm at the nanoscale level. Nanoparticles have different material characteristics because of submicroscopic size and also provide practical implementations in a wide range of fields including engineering, drug delivery, nanomedicine, environmental indentification, and catalysis, as well as target diseases such as melanoma and cardiovascular diseases (CVD), skin diseases, liver diseases, and many others.  Nanoparticles are less effective and can treat cancer by selectively killing all cancerous cells. In 2015, the Food and Drug Administration (FDA) approved the clinical trials of nanomedicine in the treatment of cancer. The characteristic properties of nanocarriers are physicochemical properties, supporting the drugs by improving solubility, degradation, clearance, targeting and combination therapy  History Petros and his colleague reported a study about mid-19th century work on nanotechnology. As they reported, polymers and drugs were conjugated in 1955 The first controlled-release polymer device appeared in 1964, the liposome was discovered by Bangham in 1965, Albumin-based NPs were reported in 1972, liposome-based drugs were formulated in 1973, the first micelle was formulated and approved in 1983, the FDA approved the first controlled formulation in 1989, and first polyethylene glycol (PEG) conjugated with protein entered the market in 1990. Further studies have produced incredibly encouraging results for treating a variety of disorders  Recent Approaches Used in Drug Carriage System for Treatment of Various Diseases Brain Drug Delivery System and Its Types Role of Nanocarriers in Alzheimer’s Disease The blood–brain barrier (BBB) The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system, thus protecting the brain from harmful or unwanted substances in the blood. The blood–brain barrier restricts the passage of pathogens, the diffusion of solutes in the blood, and large or hydrophilic molecules into the cerebrospinal fluid, while allowing the diffusion of hydrophobic molecules (O2, CO2, hormones) and small non-polar molecules. Cells of the barrier actively transport metabolic products such as glucose across the barrier using specific transport proteins.  Malignant brain tumors carry a poor prognosis, and therapeutic treatment is limited by BBB impermeability. Glioblastoma is the most common brain malignancy and represents the most aggressive form of glioma Despite the combination of surgery, radiation, and chemotherapy, overall outcomes remain poor for patients, with a 5 year survival rate of nearly 32% for malignant brain tumors, which decreases to 5% for glioblastoma. The BBB remains impermeable to nearly all large macromolecules and excludes nearly 98% of small-molecule drugs from the brain, limiting available therapeutic regimens  To enhance drug delivery for the treatment of neurological diseases, several delivery technologies to circumvent the BBB have been developed in the last few years. Among them, nanoparticles (NPs) are one of the most versatile and promising tools. The characteristics of NPs that facilitate BBB penetration, including their size, shape, chemical composition, surface charge, and importantly, their conjugation with various biological or synthetic molecules such as glucose, transferrin, insulin, polyethylene glycol, peptides, and aptamers Properties of Nanoparticles Size and Charge of NPs NPs are small molecules ranging in size from 1 to 1000 nm. Their small size is advantageous for crossing the BBB, and studies have shown increasing permeability through BBB gaps as NP size decreases, with essentially no permeability Ligands and Functional Groups The surfaces of NPs can be conjugated with specific ligands, including peptides, proteins, antibodies, and surfactants, to enhance BBB crossing by improving circulation time or by binding to endothelial receptors above 200 nm  Glucose Conjugation of NPs with glucose or related derivatives enhances BBB penetration by leveraging their binding affinity to specific glucose transporters on the endothelial cell surface. Specifically, glucose transporter type 1 (GLUT1) constitutes the subtype that is mainly expressed in the brain endothelium and principally responsible for glucose uptake. Glucose-coated gold NPs have been shown to be transferred three times faster in cerebral endothelial cell lines compared to non-brain endothelial cell lines  Transferrin Peptides and proteins, can be added to NP surfaces to improve transcytosis by targeting specific cellular receptors on the BBB, as well as targeting specific tissue. These ligands are often termed “Trojan horses” as they are recognized and internalized by BBB receptor-mediated transport systems along with their associated NP Transferrin is an essential iron transporter abundant in the BBB endothelium, rendering it a good mediator for targeted drug delivery in the brain. NPs conjugated with transferrin receptor (TfR)-targeting ligands or antibodies can promote their transcytosis across brain endothelial cells via receptor-mediated endocytosis.  PEGylated albumin NPs with anchored transferrin on their surface have shown increased uptake and localization in the brains of healthy Wistar strain albino rats when intravenously administered. Gold NPs with transferrin conjugation enhanced brain localization when systemically administered to BALB/c mice, and a larger amount of transferrin enabled strong attachment of gold NPs to brain endothelial cells Insulin Insulin-coated gold NPs (INS-GNPs) were synthesized to serve as a BBB transport system. INS-GNPs were found in mouse brains at five times greater concentrations than control untargeted GNPs. Peptides Conjugating peptides with NPs enables them to bind to receptors and other proteins expressed on BBB endothelial cells, facilitating penetration of the BBB. Typical examples of peptides targeting receptors that have been used in brain disorders include the RGD peptide targeting αvβ3-integrin, which is highly expressed on tumor tissues Recent advancement Under the most pathological circumstances of diseases such as strokes, seizures, multiple sclerosis, AIDS, diabetes, glioma, Alzheimer’s disease, and Parkinson’s disease, the blood–brain barrier (BBB) is disrupted. An important reason for the breakdown of the blood–brain barrier is the remodeling of the protein complex in intra-endothelial junctions under the pathological conditions. Normally, the blood–brain barrier acts to maintain blood–brain homeostasis by preventing entry of macromolecules and micromolecules from the blood. If a drug crosses the BBB, it restricts accumulation of the drug in the intracerebral region of brain, and bioavailability is reduced, due to which brain diseases cannot be treated.  Therefore, the optimal drug delivery system (DDS) is a cell membrane DDS, virus-based DDS, or exosome-based DDS designed for BBB penetrability, lesion-targeting ability, and standard safety. For the cure of brain diseases, the nanocarrier-assisted intranasal drug carriage system is widely used. Now, at the advanced level, drugs poorly distributed to the brain can be loaded into a nanocarrier-based system, which would interact well with the endothelial micro vessel cells at the BBB and nasal mucosa to increase drug absorption time and the olfactory nerve fibers to stimulate straight nose-to-brain delivery , thus greater drug absorption in brain parenchyma through the secondary nose-to-blood-to-brain pathway  The current strategies used are viral vectors, nanoparticles, exosomes, brain permeability enhancers, delivery through active transporters in the BBB, alteration of administration route, nanoparticles for the brain, and imaging/diagnostics under diseased conditions  Types of Nanoparticles The classes of nanoparticles listed below are all very general and multi-functional 1) Solid lipid nanoparticles (SLNs) 2) Liposomes 3) Nanostructured lipid carriers (NLC) 4) Fullerenes 5) Nanoshells 6) Quantum dots (QD) 7) Super paramagnetic nanoparticles  Polymeric nanoparticles Polymer nanoparticles refer to solid particles composed of macromolecular polymers, with particle size ranging from 10 to 1000 nm. Polymer nanoparticles can protect the encapsulated macromolecules from enzymatic degradation and change the dynamic behavior and tissue distribution of the encapsulated drugs in vivo.  Polymer-based nanoparticles are colloidal systems made up of natural or synthetic polymers. They furnish significant advantages over other nanocarriers such as liposomes, micelles and inorganic nanosystems Langer and Folkman were the first to demonstrate the controlled release of macromolecules using polymers, which allowed the development of antiangiogenic drug delivery systems for cancer therapy  The first polymers used to develop polymeric nanoparticles (PNs) were non-biodegradable polymers, such as poly(methyl methacrylate) (PMMA), polyacrylamide, polystyrene, and polyacrylates. The nanosystems made up of these materials exhibited a rapid and efficient clearance, but chronic toxicity and inflammatory reactions were observed.  The drugs can not only be dissolved or encapsulated in the nanoparticles but also be bound or adsorbed on the surface of the polymer nanoparticles. Advantages : Low toxicity, good biocompatibility, and biodegradation at specific sites are the main advantages of polymer nanoparticles as drug carriers  Biodegradable polymers include synthetic polymers such as poly(D,l-lactide) (PLA), poly(D,L-glycolide) (PLG), co-polymer poly(lactide-co-glycolide) (PLGA), polyalkylcyanoacrylates, poly-Ɛ-caprolactone. They are considered safe and a few biodegradable polymer products have been approved by the US Food and Drug Administration (FDA) as well as by the European Medicines Agency (EMA) for pharmaceutical application Non-synthetic biodegradable polymers, chitosan alginate gelatin zein albumin Physico – Chemical Properties  Drug delivery The drug dissolved, entrapped, encapsulated or attached to a nanoparticles matrix. Depending upon to the method of preparation, nanoparticles, nanospheres or nanocapsules can be obtained. Nanocapsules are systems in which the drug is confined to a cavity surrounded by a unique polymer membrane, while nanospheres are matrix systems in which the drug is physically and uniformly dispersed.  In recent years, biodegradable polymeric nanoparticles, particularly those coated with hydrophilic polymer such as poly (ethylene glycol) (PEG) known as long-circulating particles, have been used as potential drug delivery devices because of their ability to circulate for a prolonged period time target a particular organ, as carrier of DNA in gene therapy, and their ability to deliver proteins, peptides and genes  Many biomaterials, primarily polymer- or lipid-based, can be used to this end, offering extensive chemical diversity and the potential for further modification using nanoparticles. The particularly large surface area on the nanoparticles presents diverse opportunities to place functional groups on the surface.