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 amphiphilic copolymers used like poly (vinyl alcohol) (PVA), poly(ethylenimine) (PEI), poly(ε‐caprolactone) (PCL), poly‐N‐(2‐hydroxypropyl) methacrylamide (HPMA), poly(D,L‐lactic acid) (PLA), dextran, poly(D,L‐lactic‐co‐glycolic acid) (PLGA), alongside additional stealth effect offered by most widely used PEG (Utreja et al. 2020). The amphiphilic character allows poorly water‐soluble drugs to be loaded in the core with the shell providing aqueous solubility, colloidal stability, and essential stealth character. Although these nanoformulations offer improved penetrability, solubility, bioavailability, targeting through directing ligand complexed on the surface or combining monoclonal antibodies to the micelle corona, they suffer from poor in vivo stability. This effect is due to dissociation and early drug release below critical micelle concentration succeeding its administration that can also lead to drug‐related toxicity. However, stimuli‐responsive cross‐linked micelles have exhibited micellar stability and have attracted formulation scientists for the delivery of docetaxel, camptothecin, paclitaxel, cisplatin, and oxaliplatin (Ventola 2017).
The original milled organic nanocrystal, Rapamune®, approved by FDA in 2000 opened new avenues for resourceful NPs that were capable of enhancing solubility and bioavailability. Nanocrystal‐based drugs within the range of 1000 nm are peculiar because they are solely composed of drug derivatives without any carriers bound to them and are typically stabilized using polymeric steric stabilizers or surfactants. The poorly soluble organic or inorganic drugs are rendered enriched pharmacokinetic (PK)/pharmacodynamic (PD) properties by nanostructures known as nanocrystals. Nanocrystals have unique characteristics that allow them to solve problems such as increasing solubility of saturation, increased speed of dissolution, and enhanced surface/cell membrane binding. Saturation solubility increases the forces that, via biological mechanisms, such as the walls of the gastrointestinal tract, drive diffusion‐based mass transfer (Farjadian et al. 2019). The oral absorption process for nanocrystal formulations, however, is not well known and their action is not completely predictable after subcutaneous injection. They are photochemically stable and exhibit a narrow, controllable, symmetric emission spectrum. They consist of an optically energetic core enclosed by a shield that creates a physical barrier to the external environment, rendering them less vulnerable to photo‐oxidation or medium shifts. The methods of preparation of nanocrystals can be divided into top‐down and bottom‐up processes. The bottom‐up method creates nanocrystals from the solution, which requires two basic stages: nucleation and crystal formation. It mainly involves high‐pressure homogenization accompanied by grinding procedures. The top‐down methodologies comprise of high‐energy mechanical powers like milling (NanoCrystals®) or high‐pressure homogenization (IDD‐P®, DissoCubes® and Nanopure®), and the main benefit is that it is adaptable to the manufacturing scale (Lopalco and Denora 2018). Nevertheless, high energy, cost, and time used as well as impurity from grinding media are a downside of this technology, leading to unintended toxic undesirable results. Supercritical fluid (SCF) such as supercritical carbon dioxide exhibits superior physical characteristics, liquid solubilization, diffusivity similar to gas and minimal environmental effect. Thus, nanocrystals are lately prepared using SCF.
Inorganic nanocarriers have recently been used to create powerful nanocarriers for drug delivery applications attributable to easy alteration, high drug loading capability, and stability. A significant variety of inorganic materials can be used to produce NPs, such as silica, metal oxide, or metal. In particular, NPs of metal and metal oxide are being intensively studied for simultaneous therapeutic as well as imaging purposes. They are used and developed for an investigative picture of the diseased area because of the special magnetic and plasmonic properties. However, only a few inorganic NPs have been approved for clinical use, although others are still in the clinical testing stage. They are composed of a core containing the inorganic portion such as silica, gold, iron oxide, or quantum dots. A shell region consisting mostly of organic polymers (or metals) offers an adequate surface functionalization substrate or a way to protect from redundant physicochemical interactions with the biological microenvironment. Particle modification is usually done to strengthen the interaction with the biological membranes. In spite of these benefits, however, inorganic NPs have demonstrated only modest effectiveness in the treatment of disease tissues due to the crucial problems associated with the limited quantity of drug substances delivered and extreme toxicity (Lombardo et al. 2019). Gold NPs, silver NPs, and iron oxide NPs have been extensively studied in the biomedical field due to their special biochemical properties and high electron conductivity. With the approval of Abraxane® in 2005, which incorporates 130‐nm albumin NPs conjugated with paclitaxel, a shift occurred from the use of unmodified proteins to engineered particle complexes originated to enable active targeting. Protein‐based NPs include protein‐conjugated medications, formulations where the protein itself is
