(351g) Self-Assembled Triblock System to Study Drug Delivery Under Dynamic Strain

Polymer systems that can self-assemble to form ordered structures such as micelles, vesicles and physically crosslinked gels are potentially attractive for drug delivery applications. These systems are also responsive to external stimuli such as temperature, pH, ion concentration, etc., which is highly valued in drug delivery applications.  Although the drug delivery kinetics of many of these systems has been reported, comparably few of them are studied under a mechanically dynamic environment. In this study, we investigated the drug delivery properties of a self-assembled hydrogel under dynamic loading. For this purpose, triblock copolymers composed of poly(methyl methacrylate) (PMMA) endblocks and a poly(methacrylic acid) (PMAA) midblock were dissolved in a good solvent that is also miscible to water. When injected into an aqueous environment, the water-miscible solvent is replaced by water, and the polymer system self-organizes to form a physically associating hydrogel. When a model hydrophobic drug, doxorubicin (DOX), was introduced into to the system prior to self-assembly, our results showed that DOX was trapped either inside the hydrophobic aggregates during self-assembly or in the bulk network and was free to diffuse out during swelling or de-swelling. For 10wt% hydrogels, ~15% of the initial DOX (3wt%) was lost during injection (self-assembly) and 65% was released gradually for the following 14 days. The remaining ~20% was kinetically trapped in the PMMA domains. The amount of DOX released did not show any significant difference under 1% and 5% dynamic compressive strain applied at days 1, 2 and 3 for 6 hours, which was due to strong hydrophobic interactions within glassy PMMA domains. However, triethyl citrate (TC) was used (plasticizer for PMMA) to tune these interactions. The amount of DOX released increased almost 4 times with 20% (weight of PMMA) TC in steady state. This trend decreased significantly with increasing dynamic strain which was due to a significant increase in swelling under strain. For hydrogels with TC at day 3, static release was ~40% whereas it was reduced to ~35% for 1% strain and further reduced to ~20% for 5% strain. However, for gels without TC, ~10% was released for all conditions.