The second most prevalent cause of mortality among women is breast cancer, and paclitaxel (PTX) is an effective drug for its treatment. The present work aims to develop patch-based poly(ε-caprolactone) (PCL) nanofibers incorporating PTX as a localized and sustained drug delivery system. The co-deposition of poly(vinyl alcohol) (PVA) fibers during electrospinning was allowed to improve water absorption by the scaffold, which in turn facilitated the release of drug molecules. To figure out optimized electrospinning parameters and predict the optimal formulation, the quality-by-design approach was utilized. The blank mat, i.e., without drug and optimized nanofiber formulation (Fo), was characterized physiochemically using FE-SEM, XRD, FT-IR, TGA and DSC techniques. The optimization yielded a 92.7 % final product yield, indicating high process efficiency and minimum losses during electrospinning. FE-SEM studies have demonstrated that uniform nanofibers with bead-free morphology. The average fiber diameter and drug entrapment of the optimal formulation, Fo, were 547 ± 6.6 nm and 85 ± 1.73 %, respectively. Diffraction and calorimetric studies revealed a sharp decrease in the crystallinity of pure PTX and its subsequent amorphization within the nanofiber matrix. FT-IR studies showed no chemical interaction between the drug and polymers. A decrease in water contact angle from 120.4 ± 0.9 to 81.0 ± 0.8 in the Fo formulation was due to the co-spinning of PVA
this ensures proper wettability and adhesion ideal for localized delivery. The Fo nanofiber formulation demonstrated sustained PTX release for up to 17 days. The MTT assay results confirm Fo nanofibers were cytotoxic to the breast cancer cell line, MDA-MB-231, than pristine nanofibers. These findings suggest that Fo nanofiber mats could be a potential localized delivery system for PTX in breast cancer treatment, pending further in-vivo validation.