Design and development of pH-sensitive liposomes by evaluating the thermotropic behavior of their chimeric bilayers

Abstract

This study is focused on mixed/chimeric advanced drug delivery nanosystems and specifically on pH-sensitive liposomes, combining lipids and pH-responsive amphiphilic block copolymers. Chimeric liposomes are composed of hydrogenated soy phosphatidylcholine (HSPC) and two different poly(n-butylacrylate)-b-poly(acrylic acid) (PnBA-b-PAA) block copolymers with 85 and 70% content of PAA, at six different molar ratios. PAA block exhibits pH responsiveness, because of the regulative group of –COOH. Chimeric bilayers are composed of HSPC and PnBA-b-PAA. Experiments are carried out by using differential scanning calorimetry (DSC) in order to investigate their thermotropic properties. DSC indicated disappearance of the pretransition effect in all chimeric lipid bilayers, at both buffers [phosphate buffer saline (PBS) and citrate buffer], and slight changes of the main transition temperature (T m). Contrariwise, the cooperativity (T 1/2) presented alterations between the two different buffers. Chimeric liposomes have been prepared and their physicochemical characteristics have been explored in PBS and citrate buffer by measuring the size, size distribution and ζ-potential. Liposomes are found to retain the mean value of their size during the stability studies. The physicochemical characteristics and the stability assessment of chimeric liposomes are correlated with DSC measurements of mixed bilayers. The incorporation of the appropriate amount of these novel pH-responsive block copolymers affects the cooperativity and the liposomal stabilization and imparts pH responsiveness (functionality), which was confirmed by performing experiments in acidic environment (citrate buffer). In conclusion, the results from DSC measurements provide useful information regarding the quality by design process for rationally preparing mixed/chimeric liposomal platforms to incorporate bioactive molecules.