2.1.3. Drug Loading Materials

Varieties of polymers can be electrospun into diverse designs for drug delivery applications, taking account of polymer–drug compatibility and their ability to be molded to fit a range of delivery routes. When designing an optimized drug delivery system, there are many polymer factors to be considered. For instance, biocompatibility, biodegradability, mechanical properties and hydrophilicity [48]. There are many polymer varieties, such as natural and synthetic polymers, that are used for designing drug delivery systems [49,50]. A diverse range of drugs have been loaded into delivery systems, including growth factors, DNA, proteins, inhibitors, and antibiotics [33–35].

Electrospinning processes can be applied to synthetic polymers easily and with great flexibility. However, synthetic polymers affect cell affinity due to their hydrophobic nature and the smooth surfaces of their cell recognition sites. On the other hand, natural polymers show enhanced biocompatibility, and some exhibit antibacterial properties and better clinical functionality.

The group of natural polymers includes cellulose, chitosan, chitin, dextrose, collagen, silk, gelatin, etc. [51]. Lee et al. investigated the features of different polysaccharides upon electrospinning, as well as their biomedical applications, such as drug delivery, wound dressings and enzyme immobilization [52]. The studied polysaccharidses included cellulose, chitosan, alginate, chitin, starch, hyaluronic acid, dextran, and heparin. Chitosan polymer had anticancer properties due to its polycationic nature.

The quartininized form of chitosan is well known for its improved in vitro anticancer ability against Hep3B, HeLa and SW480 cells [53]. However, natural polymers lack mechanical strength, and have a relatively sudden degradation rate due to their hydrophilic nature, inhibiting their use in long-term drug delivery process. In addition, the disadvantages of immunogenicity, batch-to-batch differences, limited availability, expensive production and vulnerability to cross-contamination all limit their clinical application [54].

On the other hand, the limitations of natural polymers could be overcome in application through the use of synthetic polymers, which mainly include biodegradable polymers such as PCL, PVA, polylactic acid (PLA) and Polyglycolic acid (PLGA). These synthetic polymers can be degraded via enzymolysis or hydrolysis. These materials are therefore of great importance in drug delivery, as drug delivery for the tissue regeneration process can take time; also, tissue regeneration can occur [55]. The rate of degradation depends on the sustained release of the drug, such that the degradation rate can be controlled by changing parameters such as the ratio of amorphous to crystalline segments of polymers and polymer blend compositions [41,42]. Synthetic polymers have many advantages in comparison to natural polymers, as they are inexpensive, have excellent mechanical properties and tunable degradation, as well as exhibiting great durability. However, they also have disadvantages, such as lack of cell-specific recognition sites due to their smooth and hydrophobic surfaces.

The production of novel composite fibers through the combination of synthetic and natural polymers could reduce the disadvantages [56,57]. The combination of natural and synthetic polymers would help in the formation of a fiber that was the same as the extracellular matrix, with outstanding mechanical properties and adjustable biodegradability. For example, PLGA-gelatin was fabricated by blending electrospinning for the drug delivery of fenbufen (FBF) [58]. These blended scaffolds have

optimized mechanical properties, degradation rates and bioactivites. However, the drug release profile could be controlled by increasing the volume of PLGA in the blend. This would make the scaffolds more hydrophobic, resulting in a slower degradation rate. In another paper, composite scaffolds were prepared through a combination of PCL-gelatin, resulting, because PCL is a hydrophobic polymer, in tunable hydrophobicity, degradation rate, and mechanical properties.

Simultaneously, gelatin provided cellular attachment and adhesion of bone marrow derived from human mesenchymal stem cells (hMSCs). Thus, these types of tunable properties could result in promising scaffolds for drug delivery applications and tissue engineering systems [59]. While designing a system for the sustained release of a drug, many factors contribute to the efficient release of drug from the polymer scaffolds. These elements include the degradation and wettability of the polymer scaffolds, the type of drug and the drug loading type.

For the sustained release of the drug, the most important factor is the drug loading type. There are many types of loading, including co-axial electrospinning and multilayer electrospinning, which shows a controlled release of the drug over a longer term. The sustained release of the drug depends on the following factors in coaxial electrospinning: the thickness of the shell layer, porosity, degradation rate of the shell fiber, the hydrophobicity of the scaffolds, etc. On the other hand, in multilayered electrospinning, the drug release kinetics depends on the scaffold porosity, the thickness of the outer layer, the hydrophilicity of the scaffold, etc. The following sections describe co-axial electrospinning and multilayered electrospun scaffolds prepared by PVA hydrophilic and PCL hydrophobic polymers incroporating various drugs.
