화학공학소재연구정보센터
Journal of Colloid and Interface Science, Vol.535, 505-515, 2019
Reversibly core-crosslinked PEG-P(HPMA) micelles: Platinum coordination chemistry for competitive-ligand-regulated drug delivery
Hypothesis: The presence of pendant thioether groups on poly(ethylene glycol)-poly(N(2-hydroxypropyl) methacrylamide) (PEG-P(HPMA)) block copolymers allows for platinum-mediated coordinative micellar core-crosslinking, resulting in enhanced micellar stability and stimulus-responsive drug delivery. Experiments: A new PEG-P(HPMA) based block copolymer with pendant 4-(methylthio)benzoyl (MTB) groups along the P(HPMA) block was synthesized by free radical polymerization of a novel HPMA-MTB monomer using a PEG based macro-initiator. As crosslinker the metal-organic linker [ethylenediamine-platinum(II)](2+) was used, herein called Lx, which is a coordinative linker molecule that has been used for the conjugation of drug molecules to a number of synthetic or natural carrier systems such as hyper branched polymers and antibodies. Findings: The introduction of Lx in the micellar core results in a smaller size, a lower critical micelle concentration and a better retention of the hydrophobic drug curcumin thanks to coordination bonds between the central platinum atom of Lx and thioether groups on different polymer chains. The drug release from Lx crosslinked micelles is significantly accelerated under conditions mimicking the intracellular environment due to competitive coordination and subsequent micellar de-crosslinking. Because of their straightforward preparation and favorable drug release characteristics, core-crosslinked Lx PEG-P (HPMA) micelles hold promise as a versatile nanomedicine platform. (C) 2018 Elsevier Inc. All rights reserved.