Nanotechnology in Medicine. Группа авторов

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, waxes as well as monoglycerides, diglycerides, and triglycerides. In addition, oleic acid, isopropyl myristate, vitamin E, Transcutol P, Labrafac PG, Miglyol 812 N are some of the examples of liquid lipids used to manufacture lipidic nanoparticle by any of the methods, namely microemusification, high‐pressure homogenization, solvent emulsification‐evaporation technique, solvent emulsification‐diffusion technique, high shear homogenization or ultrasonication technique, solvent injection (or solvent displacement) technique, phase inversion temperature (PIT) method, and double emulsion technique (Utreja et al. 2020).

      Polymer NPs are commonly used in nanomedical research for the delivery of various drugs. They are quickly synthesized and there is a vast volume of evidence on their effectiveness and protection. They provide many benefits over other delivery systems in terms of stability in the gastrointestinal atmosphere and the potential to shield encapsulated agents from drug efflux pumps and enzymatic degradation. They are considered promising carriers for a variety of drugs, including cancer, coronary disease, and diabetes treatments; bone‐strengthening treatments; and vaccines (Wibowo et al. 2020). Implementation of different polymers to produce NPs enables simple manipulation of their properties such as surface load, hydrophilicity and particle size, along with stimulus‐oriented regulated release of drugs. It is possible to change the surface of NPs by conjugating polymers with peptides and antibodies (Rahman et al. 2012). Biodegradable polymers that can be completely metabolized and eliminated from the body are of special interest in nanocarriers for drug delivery. Polymeric NPs are typically made up of polymers such as chitosan, sodium alginate, polylactic acid, poly (lactic‐co‐glycolic acid) (PLGA) and poly(ш‐caprolactone) (Chavan et al. 2020).

      Nanospheres are spherical polymeric matrix particles that are rigid with drug encapsulated or dispersed within the polymer matrix. Nanocapsules are vesicular reservoir polymeric structures that act as a reservoir in which the drug is spread or absorbed in a liquid core (oil/water) surrounded by a polymer (Allen et al. 2019). Dendrimers are another form of polymeric NPs that has a branched three‐dimensional structure with ease of surface adjustment and flexibility. Various properties of dendrimers, such as high degrees of branching, size uniformity, water solubility, and the inclusion of several internal cavities, make them an effective drug delivery platform. They demonstrate the ability to enhance the solubility and bioavailability of hydrophobic drugs that may be stuck in their intramolecular cavity or conjugated to their functional surface groups. These almost monodispersed technologies represent new drug delivery systems for the treatment of various diseases and conditions of the human body. A recent emerging field of therapeutic use is the synthesis of dendrimers with bioactive ligands to promote targeted delivery and improve the effectiveness of medications with the smart use of advanced pharmaceuticals and nanomedicine. However further studies are necessary to reveal the complex structure–functional relationship of ligand–dendrimer conjugates in drug delivery processes (Lombardo et al. 2019).

Hydrophobic core–hydrophilic shell structures formed by self‐assembly of amphiphilic block copolymers in the aqueous solution are nanodrugs comprising polymeric micelles. They are investigated for the delivery of various drugs (like anti‐infective, anticancer molecules), genetic material (DNA and siRNA), proteins, peptides, etc. The micelles prepared by thin‐film hydration, sonication, or dialysis technique can be tweaked to obtain various particle sizes (20–200 nm) with narrow size distribution, drug loading and release characteristics. They can be personalized to obtain slow controlled release circumventing prompt renal clearance, thereby allowing sustained circulation and accumulation due to the impact of EPR. They flaunt biocompatibility and stability attributable to numerous