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Satisfactory drug loading capacity and stability are the two main factors that determine the anti-cancer performance. In general, the stability of the micelles is reduced when the drug loading (DL) is increased. Therefore, it was a challenge to have high drug loading capacity and good stability. In this study, we introduced a hydrophilic poly (L-Lysine) (PLL) segment with different molecular-weights into the monomethoxy poly (ethylene glycol)-poly (D, L-lactide) (MPEG-PDLLA) block copolymer to obtain a series of novel triblock MPEG-PDLLA-PLL copolymers. We found that the micelles formed by a specific MPEG 2k -PDLLA 4k -PLL 1k copolymer could encapsulate docetaxel (DTX) with a satisfactory loading capacity of up to 20% (w/w) via the thin film hydration method, while the stability of drug loaded micellar formulation was still as good as that of micelles formed by MPEG 2k -PDLLA 1.7k with drug loading of 5% (w/w). The results from computer simulation study showed that compared with MPEG 2k -PDLLA 1.7k , the molecular chain of MPEG 2k -PDLLA 4k -PLL 1k could form a more compact funnel-shaped structure when interacted with DTX. This structure favored keeping DTX encapsulated in the copolymer molecules, which improved the DL and stability of the nano-formulations. The in vitro and in vivo evaluation showed that the DTX loaded MPEG 2k -PDLLA 4k -PLL 1k (DTX/MPEG 2k -PDLLA 4k -PLL 1k ) micelles exhibited more efficiency in tumor cell growth inhibition. In conclusion, the MPEG 2k -PDLLA 4k -PLL 1k micelles were much more suitable than MPEG 2k -PDLLA 1.7k for DTX delivery, and then the novel nano-formulations showed better anti-tumor efficacy in breast cancer therapy.

A Novel MPEG-PDLLA-PLL Copolymer for Docetaxel Delivery in Breast Cancer Therapy