Designing and development of omega-3 fatty acid based self-nanoemulsifying drug delivery system (SNEDDS) of docetaxel with enhanced biopharmaceutical attributes for management of breast cancer

Abstract

Self-nanoemulsifying drug delivery system (SNEDDS) is an encouraging nanoplatforms fabricated to increase the oral bioavailability of poorly-bioavailable drugs. The current study aimed to develop omega 3 fatty acid-based SNEDDS for oral delivery of docetaxel (DTX). DTX loaded omega 3 fatty acid – based SNEDDS was developed using fish oil, tween 80 and PEG 400 as the formulation composition which was then optimized via central composite rotatable design (CCRD) based quality by design (QbD) approach. The droplet size and PDI of reconstituted SNEDDS was found to be 121.50 ± 0.17 nm and 0.338 ± 1.50, respectively with −12.3 mV zeta potential. The in-vitro drug release study demonstrated that SNEDDS provided a rapid release of DTX, as compared to suspension and exhibited Higuchi kinetic model. Further, SNEDDS demonstrated 2.12-fold increased drug permeation through intestinal membrane in comparison to suspension, implying the superiority of SNEDDS over suspension. Similarly, the ex-vivo drug permeability across the goat intestine for SNEDDS was found to be approximately 1.68-folds greater as compared to suspension, which was further confirmed via confocal laser scanning microscopy. Moreover, cytotoxicity studies on MDA-MB 231 breast cancer cells indicated a cytotoxicity enhancement of DTX by SNEDDS. Therefore, our finding firmly suggests that the developed omega 3 fatty-acid based SNEDDS could serve as an effective nanoplatform for oral delivery of docetaxel for better treatment of breast cancer.