Self-associated structures and their pH dependency of dialkyl grafted poly(aspartate) derivatives

Abstract

A series of amphiphilic graft copolymers, poly($\alpha$,$\beta$-dimethylaminoethyl aspartamide) grafted with didodecyl chains with different degree of substitution (DS), were successfully synthesized and confirmed by $^1H-NMR$ and FT-IR analysis. An appropriate amount of 2-hydroxypyridine was involved in synthetic reaction in order to increase the grafting reactivity of didodecyl chain. Self-assembled structures of synthesized polymers in aqueous solution were induced by direct dissolution method. At the same polymer concentration condition, the morphologies of self-aggregates were changed from spherical micelles to wormlike micelles, and finally to vesicles in order of DS of didodecyl chains. Those self-aggregates were characterized by TEM, DLS, and Zeta potential measurement and their structure change could be explained in terms of packing parameter and backbone flexibility. In addition, a broad transition from spherical micelles to vesicles was observed with didodecyl chain systems compared to single dodecyl chain systems within the same range of grafted dodecyl chain numbers. Structural transition also can be induced by controlling pH. In this study, vesicles were transformed into spherical micelles (or wormlike micelles) through reassembly at different pH solution. As pH increased or decreased, electrostatic repulsion between each head groups became stronger and that resulted in an increase of head group area, which meant the decrease of packing parameter. Structural transition from vesicles to spherical micelles (or wormlike micelles) could be explained based on this mechanism. Self-aggregates of PDMAEA-g-$diC_{12}$ had great potential for stimuli drug carriers. We prepared DOX-encapsulated three different self-assembled structures from PDMAEA-g-$diC_{12}$ and their pH-dependent drug release was investigated. Release of DOX from self-aggregates of PDMAEA-g-$diC_{12}s$ at mildly acidic pH was significantly faster compared to at physiological pH. It...