Nanotechnology in Medicine. Группа авторов
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1.3.2 Drug Delivery
Nanotechnology offers various nanostructures/nanoformulations in the field of nanomedicine with exceptional physical, chemical, mechanical, electrical, magnetic, and biologic properties. Nanomaterials as a key component of nanomedicine extend many benefits due to their nanoscale properties as shown in Figure 1.1. Medical developments in cancer are among the most promising treatment methods in nanomedicine. So, the additional emphasis on cardiovascular, autoimmune, psychiatric, viral, and genetic and rare diseases is a positive development within the scientific community in nanomedicine. Another new field of high promise for nanomedicine is RNA‐based synthetic vaccines (De Jong and Borm 2008; Utreja et al. 2020).
In recent years, nanomedicines have been well known because nanostructures can be used as delivery agents by encapsulating or adding medicinal drugs and distributing them more specifically with a controlled release to target tissues. More than 50 nanoformulations have been approved by the FDA since 1995 and are currently on the market for a variety of indications. The commonly approved nanoformulations are liposomes, nanocrystals, iron colloids, protein‐based NPs, nanoemulsions, and metal oxide NPs. The recent acceptance of three primary nanomedicine drugs (e.g. Onpattro®, Vyxeos®, and Hensify®) by the FDA has demonstrated that the field of nanomedicine is specifically capable of developing products that transcend crucial obstacles in conventional medicine in a special manner (Martins et al. 2020). It also offers new drug‐free clinical effects through the use of pure physical modes of action within the cells, which thereby allows a difference in the lives of patients. In addition, new clinical applications are introduced commercially owing to nanomedicine formulations currently in clinical trials (above 400) unaided or jointly with foremost technologies including microfluidics, biotechnology, photonics, information and communication technology, advanced materials, biomaterials, smart systems, and robotics. Colloidal particles composed of macromolecular compounds in the 1–500 nm size range are NPs that are carriers in which either the active material is dissolved, encapsulated, or adsorbed into the matrix uniformly (Germain et al. 2020).
Figure 1.1 Nanoscale properties and allied benefits of nanomaterials in nanotherapy.
Liposomes are one of the most studied advanced nanoformulations, first described in 1965 for medical applications. They are biocompatible bilayered structures (single or multiple) of 50–500 nm size range composed of either or both synthetic and natural lipids that imitate cell membranes with an empty aqueous interior core. They are classified as multilamellar, oligolamellar, and unilamellar depending upon structural parameters or the number of bilayers formed and the diameter of the resultant vesicles as well as the method of preparation. They are widely used and researched nanoformulations owing to their unique properties and capacity to carry and deliver both hydrophilic as well as hydrophobic therapies in the aqueous core and lipophilic bilayer, respectively. These nanostructures are also considered to boost biodistribution and to make encapsulated medicines, such as low‐molecular weight drugs, imaging agents, nucleic acids, proteins, and peptides, safe in the harsh bioenvironment of ill tissues (Vanza et al. 2020). The biological molecules like monoclonal antibodies, enzymes, and antigens can be delivered by conjugation as ligands on their surfaces (Zeb et al. 2020). Liposomes can exhibit high circulation time, sustained exposure to the site of action, strong diffusion, and penetration activity due to their unique physicochemical properties. However, clearance by RES (reticuloendothelial system), immunogenicity, and opsonization are obstacles in the use of liposomes for drug delivery. However, factors such as EPR effect aspire to improve the functioning of liposomes as drug carriers. Their simplicity of surface alteration makes them more popular in the distribution of medications (Utreja et al. 2020). PEGylated liposomes are developed by surface modification of lipid bilayer through polyethylene glycol (PEG) and are also known as long‐circulating liposomes or stealth liposomes. This decreases the uptake of liposomes by RES due to steric repression of hydrophobic and electrostatic interactions with plasma proteins or cell, thus avoiding its clearance. Various investigators have shown that moderately PEGylated liposomes have increased stability of drugs with longer blood circulation time, poor plasma clearance, and low volume of distribution (Gabizon et al. 1994; Bobo et al. 2016). The liposomal delivery vehicles are expected to change drastically by the transformation of conventional liposomes into novel types such as stealth liposome, targeted liposome, and theranostic liposome. The latter is an assemblage of the previous three forms of liposomes, encompassing medicinal, imaging, and targeting molecules. The active molecule can be encapsulated in the liposome after (active approach) or during (passive approach) its formation through procedures like thin layer hydration, mechanical agitation, solvent evaporation, solvent injection, solvent dispersion, detergent removal method, and the surfactant solubilization (Eloy et al. 2014).
Accumulation of lipid vesicles at the desired location is a prerequisite for the release and absorption of the encapsulated drug besides enhanced bioavailability. The EPR effect originate passive targeting and many approved nanoliposomal formulations (e.g. Doxil®, Lipodox®, DaunoXome®, Onivyde®, etc.) have successfully increased distribution to the diseased states based on this strategy (Caster et al. 2017). However, nanoliposomes can be synthesized by incorporating antibodies, ligands, etc. on their surface for targeted and extended delivery of drugs to organs or tissues, so that the therapeutic effect is obtained only on diseased cells sparing the normal cells. Stimuli‐responsive liposomes (pH‐sensitive, temperature‐sensitive, etc.) are also persuaded by utilizing lipids of differing fatty acid chain lengths. This allows the controlled release of their contents only on exposure to specific environmental conditions. The use of liposomal nanoformulations for drug delivery has had a major effect on anticancer, antifungal, analgesic pharmacology and is increasingly advancing to other categories as well (Patra et al. 2018).
Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are utilized for medicinal intention especially to target cancer and the transmission of ocular medicines. SLNs are biodegradable and biocompatible nanoscale colloidal carriers with a size range of 50–1000 nm. They are one of the nanocarrier systems to provide a highly lipophilic lipid matrix for dissolved and dispersed drugs manufactured by dispersing melted solid lipids in aqueous media or water using emulsifiers as a stabilizer. As carriers, SLNs deliver various advantages like higher drug payload, negligible in vivo toxicity, better bioavailability and stability of poorly soluble medicines and ease of large‐scale processing than liposomes and other colloidal systems (Vanza et al. 2020). They provide a biological medium to encapsulate lipotropic cytotoxic drugs in the core, shell, or lipid matrix and can be functionalized using compounds like oligosaccharides, proteins, antibodies, or ligands for receptors. Nevertheless, they suffer from certain restrictions that comprise of high water content required to disperse, drug leakage, and low loading capacities. The above‐stated problems related to SLNs can be overcome by using second‐generation carriers NLCs. It comprises of two main components: one is a nanostructured solid lipid matrix (a combination of liquid and solid lipids) and another is an aqueous phase (containing surfactant). In contrast to SLNs, they facilitate elevated encapsulation of active molecules, give marginal drug leakage, exalted stability and versatility (Shidhaye et al. 2008). A wide range of solid lipids are commonly used in the formulation of lipid NPs, including free fatty acids, fatty alcohols, steroids,