shaped block copolymer (methoxypoly( ethylene glycol))2-b-poly(L-glutamic acid): preparation, self-assembly, and use as drug carriers

Y-shaped amphiphilic block copolymers, (methoxy-poly(ethylene glycol))(2)-block-poly(L-glutamic acid) ((mPEG)(2)-PGA) and its precursor (methoxy-poly(ethylene glycol)(2)-block-poly(gamma-benzyl-L-glutamate) ((mPEG)(2)-PBG), were prepared in three steps: (1) macroinitiator (methoxy-poly(ethylene glycol))(2)-NH2 ((mPEG)(2)-NH2) was synthesized by coupling two methoxy-poly(ethylene glycol)s with serinol and diisocyanate. (2) (mPEG)(2)-PBG was synthesized by ring opening polymerization of gamma-benzyl-l-glutamate-N-carboxyanhydride initiated with the macroinitiator ((mPEG)(2)-NH2); (3) the protective benzyl groups in (mPEG)(2)-PBG were removed to obtain (mPEG)(2)-PGA. The properties of both (mPEG)(2)-PBG and (mPEG)(2)-PGA were characterized by H-1 NMR, FT-IR, GPC, and DLS. In aqueous solution (mPEG)(2)-PBG tends to form more stable micelles compared to linear mPEG-PBG copolymer. The size of (mPEG)(2)-PBG decreases with increasing length of hydrophobic PBG in (mPEG)(2)-PBG. Paclitaxel and cisplatin were grafted onto (mPEG)(2)-PGA to form (mPEG)(2)-PGA-PTX (MPTX) with a grafting ratio of near 90% and (mPEG)(2)-PGA-Pt (MPt) conjugates with a loading efficacy of 15% (w/w). MPTX can greatly improve the solubility of PTX. Both conjugates can self-assemble into micelles with a mean diameter of about 50 nm and show enhanced anti-cancer activity against MCF-7, HeLa, and SMMC cell lines. The in vivo anticancer evaluation in mice shows MPt showed a desirable antitumor activity and allowed us to deduce the system toxicity. Therefore, both MPTX and MPt have a great potential as a polymer drug in cancer chemotherapy.