# Poly(lactic acid)-Based Electrospun Fibrous Structures for Biomedical Applications
## 8 Biomedical Applications of PLA-Based Nanofibrous Structures
### Drug Delivery
In the hydrophilic Dox-HCl/PLA mixture, there was a larger agglomerate on the fiber surface or inside the fiber due to poor drug-polymer compatibility (Figure 14a). In this way, the drug is released so fast because of the accumulation of the drug at the surface of the fibers. The hydrophobic free doxorubicin was perfectly dispersed in the PLA matrix (Figure 14b) but the drug release was very slow. Dimethyl sulfoxide was used to solve the Dox-HCl, so then the drug mixing in the polymer matrix improved, and the electrospinning fibers containing drugs with uniform distribution in the polymer matrix were obtained (Figure 14c). The release of the drug from such fibers was very low and this low release caused low toxicity to hepatocellular carcinoma. [PERSON] et al. [108] developed doxorubicin-loaded PLA (PLA/DOX) nanofibers with a defined release mechanism. Some electrospinninging parameters, such as distance, concentration, temperature, flow rate, and applied voltage, on the average diameter of PLA/DOX nanofibers, were investigated. The results of DSC showed that DOX was effectively loaded in the nanofibers. In vitro results showed that diffusion is the prevailing drug release mechanism for drug-loaded fibers. Figure 14: Illustration of doxorubicin drug release mechanisms from a PLA fiber matrix. (**a**) PLA–HCl; (**b**) PLA–base; (**c**) PLA–HCl (DMSO). M1, dissolution of drug molecules; M2, water permeation followed by drug diffusion; M3, polymer degradation followed by drug dissolution/diffusion. Reproduced from an open access paper [107], distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported Licence. [PERSON] et al. [103] investigated the possibility of mixing carvacrol (CAR) in PLA nanofibers; they effectively formulated PLA nanofibers that are capable to hold the dispersed CAR. The results demonstrated that PLA and CAR have good compatibility. CAR was released regularly from nanofibers and caused an inti-microbial activity up to 144 h. More than 60% of total collective CAR was released after 6 h when the samples were immersed in KBS at 37 \({}^{\circ}\)C. At the end of the examination, the total released CAR was about 90% of the loaded amount. The novel Dexamethasone releasing PLLA/Pluronic P123 multilayer nanofibers constructed by [PERSON] et al. [117] are ideal for drug delivery usage. The drug was loaded in the central layer. The scaffolds constructed have appropriate surface-layer properties, but with various mechanical strengths and osteogenic proliferation and differential. The drug release profiles of the scaffolds were entirely various: single layer scaffolds displayed burst release on the first day, whereas multilayer scaffolds a controlled delivery of Dexamethasone with better osteogenesis. Therefore, the existence of a layer covering the drug-loaded layer is necessary for the controlled release of drugs and or bioactive molecules at the position of scaffold implantation. PEG is a hydrophilic polyether that is easily accessible in the market in various molecular weights. PEG with different molecular weights of 2000, 6000, 10,000, and 20,000 g/mol were selected as model molecules for investigating the effect of molecular weight on the release rate and the total released quantity. PEG has a significant effect on drug release; in one study, PEG was mixed into the polymer solutions and was included in PLA nanofibers through electrospinning. The release behavior of these molecules was investigated in water. The release experimental investigations showed two different styles: the release rate is depended on the molecular weight of model PEGs and the type of nanofibrous polymer. Large molecules were released very fast with the compression of small molecules. The release rate and total released quantity are affected by the molecular weight of incorporated molecules [109]. The combination of electrospinning and electrospray techniques for the fabrication of 3D polymeric and composite nanofibrous scaffolds creates added value for final product applications [124].