2.1.1. Drug Loading Types

Electrospinning has different drug loading types, which determine the diverse structure and drug release kinetics. The drug loading procedure in electrospinning can be executed in different ways, including co-electrospinning, multi electrospinning, side-by-side electrospinning, co-axial, surface immobilization and emulsion electrospinning (Figure 2). In co-electrospinning, the drug molecules are mixed with the polymer solution before electrospinning. These electrospun fibers provide a uniform distribution of drugs/biomolecules and high drug/biomolecule loading. However, the biomolecule properties can be negatively affected when they are directly exposed to high voltage. On the other hand, blend electrospinning and side-by-side electrospinning help to solve the issue of drug and molecule solubility in common solvents. Moreover, multi-jets with more than two spinnerets represent a way of protecting the bioactivity of the drug. In addition, surface immobilization is another method, in which drug molecules are covalently bonded with the scaffolds via chemical or physical immobilization methods. In these chemical methods, the surfaces of the nanofibers are changed by introducing amines, carboxyl, hydroxyl or thiol; the physical methods involve the incorporation of Van der Waals, electrostatic and hydrophobic interactions. These methods of immobilization retain biomolecular activity, but the drug molecules in all electrospinning processes exhibit burst release kinetics. To overcome this, co-axial and emulsion electrospinning processes were introduced. Co-axial and emulsion electrospinning processes have been gaining increasing interest recently due to their promising ability to shield the biomolecules with the core and to minimize the drawback of the initial burst. They provide sustained release of the drug by minimizing the initial burst release by controlling the thickness and composition of the shells. The core/shell structure is generated utilizing a single-nozzle electrospinning unit employing emulsion input, commonly named emulsion electrospinning [42]. Another means of drug loading for sustained release of a drug is layer by layer, via the addition of drug in between the electrospun scaffolds; controlled release is promoted by the shield provided by the layer of polymer scaffolds. Therefore, co-axial electrospinning and multilayer electrospinning drug loading types provide a more sustained and controlled release of the drug.

**Figure 2.** Schematic representation of different types of electrospinning processes. Reproduced with permission from [42]. Royal Society of Chemistry, 2015.
