**1. Introduction**

Enormous amounts of research and exploration of disorders and diseases have helped us to achieve an appropriate dosage system to stabilize a patient's health [1,2]. Conventional drug delivery systems such as salting-out (salting-out agent required), supercritical fluid technology (capillary nozzle and a supercritical fluid required), dialysis (capillary nozzle and a supercritical fluid required), solvent evaporation (surfactant required), and nanoprecipitation (non-solvent for the polymer required) are also used [1]. Moreover, conventional drug delivery systems have several deficiencies such as reduced patient compliance, shorter half-life of drugs, and high peak, etc. There is, thus, increased interest amongst scientists in developing beneficial methods to improve drug delivery systems as time passes.

A hundred years ago, Paul Ehrlich proposed the idea of tiny-drug loaded magic bullets. Later, the concept of a submicron drug delivery system was conceived by Kumar and Banker in 1996. Among these carriers, liposomes and micro/nanoparticles have been the most widely considered. Liposomes present a few technological limitations, such as poor stability, poor reproducibility, and low drug encapsulation efficiency. This technology is suitable for low molecular weight drugs. Hence, the polymeric nanoparticle drug delivery system has been proposed as an effective alternative drug delivery system to the conventional system [3]. Scheme 1 illustrates the general preparation methods for nanoparticles and their applications for drug delivery systems.

Brachais et al., in 1998, prepared a solid dispersion method to synthesize an orally-controlled drug release system. They used a biodegradable hydrophobic matrix, poly (methyl glyoxylate), and a water-soluble drug, metoprolol. Jeong et al., in 1999, studied the star-shaped block copolymers using bio-degradable polyethylene oxide and poly (L-lactic acid), in which copolymers exhibit reversible sol-gel transition [4]. Avnesh Kumari et al., in 2010, reviewed biodegradable nanoparticles such as chitosan, gelatin, poly(lactic-co-glycolic acid), Polycaprolactone, PLA(Poly Lactic acid), and gelatin as having better encapsulation properties for drug release [5]. In 2014, Carlotta Marianecci et al. presented a review on surfactant vesicles, which generated interest among the scientific community in the last decades. They studied how niosomes, which are self-assembled vesicular nanocarriers for the drug delivery system, overcome the side effects of liposomes due to their less-toxic effect, are stable, and have a low cost [6]. Jeong et al., in 1999, studied star-shaped block copolymers using bio-degradable polyethylene oxide and poly (L-lactic acid); these copolymers exhibit reversible sol-gel transition.

**Scheme 1.** Representation of the general method of synthesis/preparation of nanoparticles.

Therefore, exponential growth in the development of modified drug delivery systems is essential for dosage form improvement. Modified drug delivery systems have been considered to transport active agents in higher demand due to their delivery process, programmed target-specificity, cellular uptake, clearance, toxicity, metabolism, pharmacokinetics, excretion, greater half-life in terms of repeated administration of drugs and improved patient health [7]. The successful drug delivery systems are designed to increase the efficiency of the drug in the body by using external or internal stimuli, and nanocarrier features are modified according to the physicochemical properties of drugs [2]. Indeed, drugs essentially require highly effective, controlled release along with biocompatible encapsulation to increase patient compliance [2].

Due to the rapid increase in research in the field of polymer science, the structural backbone for the development of novel and modified drug delivery systems is considered [8]. Primarily, non-biodegradable polymeric nanoparticles, such as polymethylmethacrylate, polyacrylamide, and polystyrene, have been used for drug delivery systems; however, a huge level of toxicity and detrimental health consequences from non-biodegradable polymers have been observed. Therefore, biocompatible polymers, due to their immense properties and growth, are under discussion within the scientific community for in vivo and in vitro diagnosis and treatment of diseases [8–10].

Polymeric nanostructured materials (PNMs) have played a vital role in therapeutic diagnosis and treatment of diseases [11–14]. Through the development of PNMs as new biomaterials, significant improvement in the quality of healthcare can be achieved, due to the better accuracy and reliability in diagnostics, more effective targeting of therapeutic agents, and improved usability of scaffolds for tissue engineering and regenerative medicines [15–17]. PNMs, including micelles, polymerases, nanoparticles, nanocapsules, nanogels, nanofibers, dendrimers, brush polymers, and nanocomposites can be prepared for delivery via a variety of pathways. Their properties, such as stability, size, shape, surface charge, surface chemistry, mechanical strength, and porosity can be tailored toward specific functionalities that are required to meet the needs of the targeted biomedical application. As a result, the development of biomedical PNMs has attracted plenty of research in the field, and a vast number of recent publications can now be found in the literature.

An amalgamation of nanoparticles with polymer science has led to a new direction in the field of biomedical engineering, packaging, food processing, tissue engineering and improved treatment for water-insoluble and soluble drug delivery systems. Nanoparticles are characterized by a particle size range of 1 to 100 nm. 'Nano' is derived from the Greek word 'Nanos' which means dwarf [9–18]. The basis of the morphology, chemical and physical properties of nanoparticles relate to the different derivative materials such as ceramic, liquid, metal, semiconductors, and carbon-based nanoparticles, which may be biodegradable or non-biodegradable [19]. Nanoparticles or smart polymers are under consideration due to their advantages, including a greater surface to charge ratio, ease of characterization and ease of synthesize, the fact that they are reproducible, stable after administration, non-immunogenic, and have significant absorption properties. These unique features make them of huge interest as carriers for drugs and inexpensive formulation [20]. The effective therapeutic transformation from a macro- to a nano-drug delivery system relates to the controlled release of a drug on a target as compared to the less targeted release of conventional drug delivery systems [21]. Therefore, depending upon the method of synthesis, nanomedicines can be one of two types, i.e., nanospheres which encapsulate drugs into a smart polymeric shell (nanopolymer shell) and nanocapsules in which drugs are dispersed into the polymeric matrix [22,23]. The representation of both types of nanomedicines is shown in Figure 1. The synthesis of a nano-drug delivery system depends upon the targeted part of the body and organ. The biocompatibility and degradability of nanomedicines must be considered as they carry DNA, drugs, and proteins to the targeted area [24]. The size and surface-to-charge ratio of polymer nanoparticles play a significant role in maintaining systematic flow across the cell membrane [25,26]. The efficiency of the drugs depends upon the properties of the polymer, nanoparticles, solvent, and encapsulation method.

**Figure 1.** Schematic of nanomedicines: nanospheres and nanocapsules.

Smart polymers or nanoparticles play an essential role in the treatment of chronic diseases such as cancer, diabetes, cardiovascular and neurodegenerative disorders [27,28]. Various natural and synthetic polymers play a significant role in a targeted drug delivery system [29,30]. Some natural and synthetic polymeric materials have easy accessibility, biocompatibility, bio-decomposition properties, and easy modification. Reactive groups, such as amino, hydroxyl and carboxylic groups present on polymers, easily interact with other synthesized materials, thus endowing new modified hybrid materials with improved physical and chemical properties [31–33]. There are various types of natural polymers such as proteins, polysaccharides, peptides, collagen, albumin, gelatin, chitosan, alginate, fibroin, and synthetic polymers such as polylactic acid (PLA) and polyglycolic acid (PGA) [34]. Synthetic and natural polymers have their disadvantages and advantages. Biocompatible polymers are mostly preferred because they are economical, easily prepared, and extremely stable in the biological fluid; they show better proliferation, adhesion, and target usage with high efficiency [34]. Nanomaterials usually consist of carbon-based materials such as fullerenes, carbon dots, nanodiamonds, nano-foams, carbon nanotubes, and polymers. Inorganic nanoparticles are metals such as gold, silver and metal oxides (cerium oxide, iron oxide, silicon dioxide, titanium oxide), semiconductors and metal nanoparticles [33]. Figure 2 shows the schematic of the polymer classification.

**Figure 2.** Schematic of polymer classification. Reference is taken from [35]. Copyright ©2019, Elsevier.

In general, the aim and specificity of the present review are highly important for some natural, biodegradable and biocompatible polymers. The present review covers some popular polymers such as chitosan, albumin, alginate, hydroxyapatite, and hyaluronic acid currently used for drug delivery systems. Furthermore, it provides information about the functionalization of the above-mentioned polymers to enhance their properties and develop an effective drug release system [36].
