Green Synthesis of Polycyclodextrin/Drug Inclusion Complex Nanofibrous Hydrogels: pH-Dependent Release of Acyclovir

The development of an approach or a material for wound healing treatments has drawn a lot of attention for decades and has been an important portion of the research in the medical industry. Especially, there is growing interest and demand for the generation of wound care products using eco-friendly conditions. Electrospinning is one of these methods that enables the production of nanofibrous materials with attractive properties for wound healing under mild conditions and by using sustainable sources. In this study, starch-derived cyclodextrin (hydroxypropyl-β-cyclodextrin (HPβCD)) was used both for forming an inclusion complex (IC) with acyclovir, a well-known antiviral drug, and for electrospinning of free-standing nanofibers. The nanofibers were produced in an aqueous system, without using a carrier polymer matrix and toxic solvent/chemical. The ultimate HPβCD/acyclovir-IC nanofibers were thermally cross-linked by using citric acid, listed in the generally regarded as safe (GRAS) category by the US Food and Drug Administration (FDA). The cross-linked HPβCD/acyclovir-IC nanofibers displayed stability in aqueous medium. The hydrogel-forming feature of nanofibers was confirmed with their high swelling profile in water in the range of ∼610-810%. Cellulose acetate (CA)/acyclovir nanofibers were also produced as the control sample. Due to inclusion complexation with HPβCD, the solubility of acyclovir was improved, so cross-linked HPβCD/acyclovir-IC nanofibrous hydrogels displayed a better release performance compared to CA/acyclovir nanofibers. Here, a pH-dependent release profile was obtained (pH 5.4 and pH 7.4) besides their attractive swelling features. Therefore, the cross-linked HPβCD/acyclovir-IC nanofibrous hydrogel can be a promising candidate as a wound healing dressing for the administration of antiviral drugs by holding the unique properties of CD and electrospun nanofibers.