Tailoring the Release of Paclitaxel from Electrospun Nonwovens

Implantable drug delivery devices may enhance therapeutic efficacy by allowing localized drug release, and they may overcome the drawbacks of conventional systemic treatment. Electrospun nanofibers are promising drug delivery systems due to their high surface-to-volume ratio, porosity, and easy drug encapsulation. However, controlled and sustained drug release is required to improve therapeutic efficacy and reduce toxicity. Also, the ability to tailor the release drug dose would be a useful tool for providing an optimal and individualized approach for the treatment. Therefore, the aim of the study was to analyze the possibility to tailor the release of paclitaxel (PTX) from poly(D,L-lactide-co-glycolide) (PDLGA) electrospun nonwovens by modifying the comonomer molar ratio. For this purpose, three kinds of polymers were compared with lactidyl-to-glycolidyl comonomer ratios of 86:14, 70:30, and 48:52. Also, nonwovens obtained from a blend of PDLGA and PVA were used to analyze the effect of the addition of the hydrophilic polymer on degradation and, thus, the release rate. The comprehensive analysis of the developed nonwovens was conducted through an evaluation of the morphology, in vitro degradation, and drug release process, as well as cytotoxicity. It has been observed that all kinds of the developed PDLGA nonwovens provide an extended-release profile but with different release rates, which depend on the comonomer unit ratio and molar mass of the copolymer. Moreover, the increase in hydrophilicity caused by PVA sufficiently accelerates PTX release. The biological activity of released PTX was confirmed under in vitro and in vivo conditions against 4T1 mouse mammary carcinoma. The results of the study enabled us to gain insight into the influence of polymer choice on PTX release from PDLGA ES implants, which may be helpful in their easier translation into the clinic and for better adjustment of the PTX dose for individual treatment.