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Abstract
Polymeric micelles are very attractive drug delivery systems for hydrophobic agents, owing to their readily tailorable chemical structure and ease for scale-up preparation. However, the intrinsic poor stability of drug-loaded micelles presents one of the major challenges for most micellar systems in the translation to clinical applications. In this study, a simple, well-defined, and easy-to-scale up 9-Fluorenylmethoxycarbonyl (Fmoc) and tert-butoxycarbonyl (Boc) containing lysine dendronized mPEG-PLA (mPEG-PLA-Lys(FB)2) micellar formulation was designed and prepared for docetaxel (DTX) delivery, in an effort to improve the stability of the micelles, and its physicochemical properties, pharmacokinetics, and anti-tumor efficacy against SKOV-3 ovarian cancer were evaluated. MPEG-PLA-Lys(FB)2 was synthesized via a three-step synthetic route, and it actively interacted with DTX in aqueous media to form stable micelles with small particle sizes (~17–19 nm) and narrow size distribution (PI < 0.1), which can be lyophilized and easily reconstituted in saline without significant change in particle size distribution. In vitro drug-release study demonstrated that mPEG-PLA-Lys(FB)2 micelles achieved delayed and sustained release manner of DTX in comparison with mPEG-PLA micelles. Further in vivo xenograft tumor model in nude mice DTX/mPEG-PLA-Lys(FB)2 micelles demonstrated significantly higher inhibitory effect on tumor growth than the marketed formulation Taxotere. Thus, our system may hold promise as a simple and effective delivery system for DTX with a potential for translation into clinical study.