In Vitro Investigations of Smart Drug Delivery Systems Based on Redox-Sensitive Cross-Linked Micelles

• Published in: Macromolecular bioscience Vol. 13; no. 12; pp. 1661 - 1670
• Main Authors: Cajot, Sébastien, Schol, Daureen, Danhier, Fabienne, Préat, Véronique, Gillet De Pauw, Marie-Claire, Jérôme, Christine
• Format: Journal Article Web Resource
• Language: English
• Published: Germany Blackwell Publishing Ltd 01.12.2013; Wiley
• Subjects: Animals; Architecture; Biological Transport; biomaterial; Block copolymers; Cell Line, Tumor; Cell Survival - drug effects; Cellular; Chemistry; Chimie; Construction; cross-linked micelles; Cross-Linking Reagents - chemistry; Crosslinking; cytotoxicity; disulfide bridges; Disulfides - chemistry; Drug Carriers - chemical synthesis; Drug Carriers - pharmacology; Drug Compounding; Drug delivery systems; Engineering, computing & technology; Fluorescent Dyes - chemistry; Humans; Hydrophobic and Hydrophilic Interactions; Ingénierie, informatique & technologie; internalization; Materials science & engineering; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Mice; micelle; Micelles; nanomedicine; Nanostructure; Oxazines - chemistry; Oxidation-Reduction; Physical, chemical, mathematical & earth Sciences; Physique, chimie, mathématiques & sciences de la terre; Polyesters - chemistry; Polyethylene Glycols - chemistry; Science des matériaux & ingénierie; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; smart drug delivery; Sols; smart drug delivery; internalization; cross-linked micelles; disulfide bridges; cytotoxicity
• ISSN: 1616-5187; 1022-1360; 1521-3900; 1616-5195
• DOI: 10.1002/mabi.201300250

Redox‐sensitive micelles are designed by using block copolymers of different architectures composed of a hydrophilic block of poly(ethylene oxide), and hydrophobic blocks of poly(ϵ‐caprolactone) and poly(α‐azide‐ϵ‐caprolactone). Stability of these micelles is insured in diluted media by cross‐linking their core via the addition of a bifunctional cross‐linker, while redox sensitivity is provided to these micelles by inserting a disulfide bridge in the cross‐linker. The potential of these responsive micelles to be used as nanocarriers is studied in terms of cytotoxicity and cellular internalization. The release profiles are also investigated by varying the environment reductive strength. Core‐crosslinked micelles build from reactive POE‐b‐PN3CL copolymers do not exhibit cytotoxicity, are internalized by cells, and are able to release their hydrophobic drug loading in response to the reductive environment, such as intracellular sols.