Fabrication and evaluation of Docetaxel doped ZnO nanoparticles incorporated PCL nanofibers for its hemocompatibility, cytotoxicity and apoptotic effects against A549

Abstract

Nano-structured bio-materials have been studied extensively in anti-cancer applications than free forms of the drug in recent years, for its effects even against chemo resistant cancer cells proving its promising diagnostic and therapeutic medicaments. We have developed a nanofibrous drug delivery system incorporating zinc oxide and docetaxel which shows synergistic effects of EPR (enhanced permeability and retention) and stopping the growth of cancer cells respectively in the nanofibers. Optimization of the experiments using RSM-Central Composite Design showed an R2 value of 99.72% for the PCL+ZnO+DTX nanofibers showing a good correlation between the performed experiments and the computational analysis. SEM, FTIR and XRD analysis was done and the material was proved for its morphological, physicochemical and thermal characteristics. We have also attempted to simulate a tumor microenvironment during our HPLC study wherein the drug docetaxel showed a retention time of 11.704 min at an absorbance value of 214.6 nm. PCL+ZnO+DTX nanofibers showed lower cell viability percentage of 23 at 500 µg/ml and the mechanism of apoptotic mode of death was confirmed from flow cytometry analysis with an apoptotic activity of 48.84%. An acceptable hemolysis percentage of 4.47 ± 0.15% was observed for our synthesized nanofibers enabling it an effective material for post cancer therapeutics. Thus, our fabricated penetration enhanced nanofiller and chemotherapeutic agent incorporated nano-constructs assist as a targeted delivery system in the treatment of recurrence of lung cancer.