Reversibly core-crosslinked PEG-P(HPMA) micelles: Platinum coordination chemistry for competitive-ligand-regulated drug delivery

• Published in: Journal of colloid and interface science Vol. 535; pp. 505 - 515
• Main Authors: Buwalda, Sytze, Nottelet, Benjamin, Bethry, Audrey, Kok, Robbert Jan, Sijbrandi, Niels, Coudane, Jean
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2019; Elsevier
• Subjects: Chemical Sciences; composite polymers; Controlled drug delivery; Coordination chemistry; coordination compounds; Core-crosslinked micelle; Cross-Linking Reagents; Cross-Linking Reagents - chemical synthesis; Cross-Linking Reagents - chemistry; crosslinking; curcumin; Drug Delivery Systems; drugs; free radicals; hydrophobicity; Ligands; Material chemistry; Methacrylates - chemistry; Metharcrylates; Micelles; Molecular; Molecular Structure; nanomedicine; Organoplatinium Compunds; Organoplatinum Compounds - chemistry; Particle Size; PEG-P(HPMA); platinum; polyethylene glycol; Polyethylene Glycols; Polyethylene Glycols - chemistry; polymerization; Stimulus-responsive; Surface Properties; PEG-P(HPMA); Stimulus-responsive; Controlled drug delivery; Core-crosslinked micelle; Coordination chemistry
• DOI: 10.1016/j.jcis.2018.10.001
• ISSN: 0021-9797; 1095-7103

[Display omitted] 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. 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 [ethylenediamineplatinum(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 hyperbranched polymers and antibodies. 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.