Co-delivery of docetaxel and retinoic acid by poly (ethylene glycol)-retinoic acid conjugates based micelles for synergistic prostate cancer therapy

In the present work, docetaxel (DTX) and retinoic acid (RA) co-loaded micelles were developed for synergistic prostate cancer therapy. PEG-RA and RA-PEG-RA were synthesized and subsequently used for loading of DTX and RA. The as prepared DTX/RA@RA-PEG-RA micelles exhibit smaller size and higher drug loading capacity as compared to DTX/RA@PEG-RA micelles. The in vitro drug release study shows that DTX/RA@PEG-RA and DTX/RA@RA-PEG-RA micelles exhibit similar drug release behaviours in which DTX exhibits fast release and RA exhibits sustained release. Nile red (NR) was loaded into PEG-RA and RA-PEG-RA micelles to investigate the cellular uptake of the micelles by fluorescence microscope and flow cytometry. The results show that NR@RA-PEG-RA micelles exhibit slightly enhanced cellular uptake as compared to NR@PEG-RA micelles. The cellular uptake of DTX/RA@PEG-RA and DTX/RA@RA-PEG-RA micelles determined by HPLC also show similar results. In in vitro cytotoxicity against C4-2 and 22Rv1 cells, DTX in combination with RA exhibit synergistic antitumor effect, and DTX/RA@PEG-RA and DTX/RA@RA-PEG-RA micelles exhibit enhanced cytotoxicity against C4-2 cells and similar cytotoxicity against 22Rv1 cells as compared to DTX/RA. DTX/RA@PEG-RA and DTX/RA@RA-PEG-RA micelles show significant potential for prostate cancer therapy.