Tailored drug-release from multi-functional polymer-peptide hybrid vesicles
Résumé
The synthetic semi-crystalline polymer poly(trimethylene carbonate) PTMC50 was linked to the synthetic poly(amino acid) poly(glutamic acid) (PGA(15)) using the peptide PVGLIG, known to be selectively cleaved by the tumor-associated enzyme matrix metalloproteinase 2 (MMP-2), by a combination of thiol-ene coupling and ring-opening polymerization. Stable, monodisperse, sub-micron sized polymersomes were subsequently obtained by self-assembly and characterized by dynamic and static light scattering (DLS and SLS) and transmission electron microscopy (TEM). These vesicles showed selective degradation in the presence of MMP-2 as probed by DLS. The model drug imipramine hydrochloride was loaded at 35% encapsulation efficiency by co-precipitation and displayed controlled drug-release behavior. Drug release rates showed several fold increases when exposed to pH, temperature and most significantly, to the tumor-associated enzyme MMP-2. Such structures, bearing precise location of the cleavable peptide sequence, may hold promise as future specific and controlled drug-delivery systems. (C) 2014 Elsevier Ltd. All rights reserved.