Controlling the Functionality of Block Copolymer Bicontinuous Nanospheres

Abstract

Amphiphilic block copolymers (BCPs) form self-assembled aggregates in solution with a range of morphologies including spherical micelles, cylindrical micelles, vesicles (polymersomes) and bicontinuous nanospheres. This research focuses on the formation of bicontinuous nanospheres using a number of different BCPs for use in thermo-responsive drug delivery. It has been shown previously that PEO-b-PODMA (poly(ethylene oxide)-block-poly(octadecyl methacrylate)) forms semi-crystalline bicontinuous nanospheres with a phase transition temperature (Tm) of 21.8?C. This corresponds to the melting transition of the semi-crystalline PODMA block. To increase the Tm, while maintaining all other properties, the hydrophobic monomer ODMA, was replaced with docosyl methacrylate (DSMA), which has a higher melting point. Upon self-assembly the PEO-b-PDSMA (25 wt % PEO) formed bicontinuous nanospheres. Analysis using differential scanning calorimetry (DSC) revealed the Tm of PEO-b-PDSMA in bulk and aggregate solution to be 41.3°C and 41.1°C respectively. To further demonstrate the control achieved over the Tm, random copolymers of ODMA and DSMA using a PEO macroinitiator were synthesised at varying wt % ratios of PODMA:PDSMA. DSC analysis of these polymers showed that an increase in PDSMA led to an increase in the Tm for the bulk and self-assembled samples. The controlled release of Ibuprofen from these bicontinuous nanospheres was investigated to determine the rate of release and the optimum temperature for release following a previously used method. The concentration of release was then analysed using HPLC. To incorporate acid functionality into the bicontinuous nanospheres PMAA-b-PODMA (poly(methacrylic acid)-block-poly(octadecyl methacrylate)) was synthesised (via ATRP) with hydrophilic wt % of 20 %. The self-assembled solution of PMAA-b-PODMA was analysed using cryo-TEM which revealed the presence of bicontinuous nanospheres. Another approach to incorporate acid functionality into bicontinuous nanospheres was the self-assembled of PEO-b-PS and PEO-b-PODMA followed by the alkaline hydrolysis of PEO to leave an acid end group