Development and characterisation of topotecan/quercetin loaded nanofiber based injectable nanofiber system for breast cancer management

To date, conventional chemotherapy is constrained by high effective dosing, non-specific biodistribution, systemic toxicity and acquired drug resistance due to overexpression of efflux transporters. For addressing these concerns, the present study developed an injectable nanofiber system, co-loaded with a chemotherapeutic agent, topotecan hydrochloride (TH) and a pro-oxidant efflux inhibitor, quercetin (QR), using polycaprolactone (PCL) as the carrier matrix. The intact nanofiber mats were obtained by electrospinning and then converted to a dispersed nanofiber suspension following probe sonication for local delivery. The dual drug delivery system aimed to achieve sustained and site-specific drug delivery while reducing systemic toxicity and enhancing overall cytotoxic effect. The final formulation had an encapsulation efficiency of 62.43 ± 3.43% and 78.25 ± 8.55% cumulative release for 72 h at pH 6.8. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay revealed that the developed formulation had significantly greater cytotoxicity against MCF-7 breast cancer cells than the free drug controls, which was further confirmed by intracellular reactive oxygen species levels. In vivo findings also showed enhanced antitumor activity and good pharmacokinetic and biodistribution parameters. Overall, the formulation indicated TH-QR-loaded PCL injectable nanofiber as a localised, sustained-release platform to overcome efflux-mediated resistance and enhance the therapeutic index in breast cancer management.