In this paper, the synthesis and characterization of novel amphiphilic graft copolymers based on an ?,?-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) backbone and D,L-polylactic acid (PLA) hydrophobic side chains are reported. These copolymers were obtained starting from PHEA-ethylenediamine (PHEA-EDA), which was functionalized with polysorbate 80 (PS) and/or PLA in order to obtain the PHEA-EDA-PS-PLA and PHEA-EDA-PLA samples, respectively. The degrees of derivatization, DD PS8080 and DD PLA, of PHEA-EDA-PS-PLA, calculated by 1H-NMR, resulted in being 1.2 ± 0.03 mol% and 0.54 ± 0.05 mol%, respectively, while that of PHEA-EDA-PLA was found to be 0.60 ± 0.05 mol%. Size exclusion chromatography (SEC) analysis confirmed the occurrence of derivatization, the molecularweight values being close to the theoretical ones. Polymeric micelles from PHEA-EDA-PLA and PHEA-EDA-PS-PLA copolymers were obtained by using the dialysis method and were characterized in terms of mean size, zeta potential, critical aggregation concentration (CAC), and surface composition by x-ray photoelectron spectroscopy (XPS) analysis, which demonstrated the presence of PS80 onto the PHEA-EDA-PS-PLA micelle surface. In vitro experiments demonstrated that these systems had no cytotoxic effects on 16 HBE, Caco2, HuDe and K562 cell lines, and no haemolytic activity. Moreover, both PHEA-EDA-PS-PLA and PHEA-EDA-PLA micelles were able to penetrate into Neuro2a cells and, in the case of PS decorated micelles, to escape from phagocytosis by the J774 A1 macrophages.
Micelles based on biocompatible polymers bearing polysorbate 80 potentially targetable to the CNS
MP Casaletto;
2008
Abstract
In this paper, the synthesis and characterization of novel amphiphilic graft copolymers based on an ?,?-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) backbone and D,L-polylactic acid (PLA) hydrophobic side chains are reported. These copolymers were obtained starting from PHEA-ethylenediamine (PHEA-EDA), which was functionalized with polysorbate 80 (PS) and/or PLA in order to obtain the PHEA-EDA-PS-PLA and PHEA-EDA-PLA samples, respectively. The degrees of derivatization, DD PS8080 and DD PLA, of PHEA-EDA-PS-PLA, calculated by 1H-NMR, resulted in being 1.2 ± 0.03 mol% and 0.54 ± 0.05 mol%, respectively, while that of PHEA-EDA-PLA was found to be 0.60 ± 0.05 mol%. Size exclusion chromatography (SEC) analysis confirmed the occurrence of derivatization, the molecularweight values being close to the theoretical ones. Polymeric micelles from PHEA-EDA-PLA and PHEA-EDA-PS-PLA copolymers were obtained by using the dialysis method and were characterized in terms of mean size, zeta potential, critical aggregation concentration (CAC), and surface composition by x-ray photoelectron spectroscopy (XPS) analysis, which demonstrated the presence of PS80 onto the PHEA-EDA-PS-PLA micelle surface. In vitro experiments demonstrated that these systems had no cytotoxic effects on 16 HBE, Caco2, HuDe and K562 cell lines, and no haemolytic activity. Moreover, both PHEA-EDA-PS-PLA and PHEA-EDA-PLA micelles were able to penetrate into Neuro2a cells and, in the case of PS decorated micelles, to escape from phagocytosis by the J774 A1 macrophages.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
