The combination of oral antidiabetic drugs, pioglitazone, metformin, and glibenclamide, which also exhibit the strongest anti-inflammatory action among oral antidiabetic drugs, were loaded into chitosan/gelatin/polycaprolactone (PCL) by electrospinning and polyvinyl pyrrolidone (PVP)/PCL composite nanofibrous scaffolds by pressurized gyration to compare the diabetic wound healing effect. The combination therapies significantly accelerated diabetic wound healing in type-1 diabetic rats and organized densely packed collagen fibers in the dermis, it also showed better regeneration of the dermis and epidermis than single drug-loaded scaffolds with less inflammatory cell infiltration and edema. The formation of the hair follicles started in 14 days only in the combination therapy and lower proinflammatory cytokine levels were observed compared to single drug-loaded treatment groups. The combination therapy increased the wettability and hydrophilicity of scaffolds, demonstrated sustained drug release over 14 days, has high tensile strength and suitable cytocompatibility on L929 (mouse fibroblast) cell and created a suitable area for the proliferation of fibroblast cells. Consequently, the application of metformin and pioglitazone-loaded chitosan/gelatin/PCL nanofibrous scaffolds to a diabetic wound area offer high bioavailability, fewer systemic side effects, and reduced frequency of dosage and amount of drug.

Wound dressings made from natural polymers are an important aspect of biomaterials. Proteinbased materials are less likely to instigate an immunogenic response and have the capacity to degrade in vivo, also without triggering an inflammatory response. Therefore, gelatin (GEL) was chosen and combined with bacterial cellulose (BC) to produce nanofibres and the potential of an all-natural polymer construct was determined. GEL and BC were successfully electrospun with metformin (Met) and glybenclamide (Gb) using a portable, point of need electrospinning set up. The virgin fibre group exhibited a significant effect on the proliferation of L929 (mouse fibroblast) cells but all fibre samples can safely be applied on wound site without risk of cytotoxicity. According to the results obtained by animal tests, the GEL-BC-Gb group showed better recovery than the GEL-BC-Met group. Diabetic wounds treated with GEL-BC-Met were characterized by moderate re-epithelialization and partially organized granulation tissue.Moderate to complete re-epithelialization and well-formed granulation tissue were observed in diabetic wounds treated with GEL-BC-Gb. The histologic scores obtained on day 14 confirmed that the GEL-BC-Gb group played a stronger wound-healing role compared to the GEL-BC-Met group. The highest decrease of TNF-α level was observed in the GEL-BC-Gb group at the end of the experiment but there is no significant difference between drug-loaded fibre groups.Therefore, topical administration of Met and Gb in a sustained release form has a high potential for diabetic wound healing with high bioavailability and fewer systemic side effects but Gb showed better improvement according to the results of the animal tests.

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Progesterone-loaded poly(lactic) acid fibrous polymeric patches were created for the intra-vaginal application using electrospinning (ES) and pressurized gyration (PG) to prevent preterm birth with higher bioavailability. The patches were intravaginally inserted into the rats in the final week of their pregnancy, equivalent to the third trimester of human pregnancy. Maintenance tocolysis with progesterone-loaded patches was elucidated by recording the contractile response of uterine smooth muscle to noradrenaline in pregnant rats. Both progesterone-loaded patches indicated similar results from the release and thermal studies, however, patches obtained by ES had smaller average diameters and more uniform dispersion compared to PG. Patches obtained by PG had better results in production yield and tensile strength than ES; thereby PG is better suited for scaled-up production. The patches did not affect the cell attachment, viability and proliferation on Vero cells negatively. Consequently, progesterone-loaded patches are a novel and successful treatment strategy for preventing preterm birth.

Nanofibers (NFs) offer an alternative option for the treatment of Alzheimer's disease (AD) by addressing unmet clinical problems. In this study, anti‐AD drugs, donepezil (DO) and curcumin (CUR), are loaded in polylactic acid/polycaprolactone NFs. The effect of fiber diameter on drug release behavior is mainly observed, and the successful loading of DO and CUR to NFs is demonstrated. The tensile strength of DO/CUR‐loaded NFs (DNFs) with lower fiber diameter is found to be higher. The working temperature is increased by the decrease of glass transition temperature and increase of the melting temperature after loading drugs. Furthermore, the increase in the percentage of swelling and decrease in the degradation rate for NFs are observed due to the increase of fiber diameter. Encapsulation efficiency and burst release percentages for DNFs are augmented by the increase of fiber diameter. Nevertheless, DNFs exhibit a sustained drug release manner over 2 weeks. NFs do not demonstrate a toxic effect on L929 (mouse fibroblast) cells, and additionally, they promote cell proliferation. Considering all these results, it is proven that the fiber diameter affects all characteristic features of NFs, and DNFs lead to a new and promising drug delivery system for the treatment of AD.

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