Characterization and minimization of block copolypeptide vesicle cytotoxicity using different hydrophobic chain lengths

Abstract

The previously reported amphiphilic block copolypeptide, poly(l-lysine)60-block-poly(l-leucine)20 (K 60L20), is able to form vesicles that can be manipulated to different sizes and be prepared in large quantities. This study expands upon that work by varying the length of the hydrophobic segment to optimize the vesicles so that they are monodisperse and low in toxicity. Copolypeptides with longer oligoleucine segments are found to have fewer toxic micelles, small aggregates, and unstable vesicles, and exhibit lower toxicity than vesicles formed from copolypeptides with shorter hydrophobic domains. Oligoleucine segments that are too long, however, result in rigid hydrophobic membranes that prevent the vesicular assemblies from being extruded into a monodisperse population of nanoscale vesicles. The ratio between the hydrophilic and hydrophobic segments of the amphiphilic block copolypeptide poly(L-lysine)- block-poly(L-leucine) affects the shape of the polypeptide in aqueous solution, and ultimately dictates the type of supermolecular structures that are formed. This ratio is optimized in this study in order to form vesicles that exhibit low toxicity and are monodisperse in population. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.