(583e) Controlled Release From Self-Assembled Polymer Microparticles That Are Responsive to pH and Temperature

Controlled release of biologically active molecules is of significant interest in the pharmaceutical and biomaterials fields. Benefits of controlled release mechanisms include adjustable release rate, improved pharmacokinetics, and reduction of undesirable side-effects. Among controlled delivery systems, oral delivery using biocompatible polymer particle excipients has received significant attention [1]. In this study, particles were formed from a selectively water-soluble cellulose ether with a lower critical solution temperature (LCST) close to body temperature [2]. Above the LCST, hydrophobic polymer interactions dominate resulting in self-aggregation of polymer chains. The polymer chains were cross-linked above the LCST, and formed hydrated microgel particles when cooled below the phase transition temperature. Particles were encapsulated with a carboxylated polymer, resulting in a pH-responsive core-shell configuration. Controlled release from the particles was investigated using hydrophilic small-molecules as entrapped solutes. The efficacy of particle formulations was measured through release kinetics performance in comparison to aqueous solutions of the hydrophilic molecules. Sustained release from the particles and control was analyzed in vitro at temperatures above and below the LCST using a horizontal static diffusion cell. The empirical data were found be in good agreement with a mathematical model developed for in vitro release kinetics experiments.

REFERENCES

1. Kost, J.; Langer, R. Responsive polymeric delivery systems. Adv. Drug Deliv. Rev. 2001, 46, 125-148.
2. Sexton, F. A.; Krishnan, S.; Vendra, V. K. Sustained release of nutrients in vivo. U. S. Pat. Appl. Publ., US 20090155409 A1 20090618 (2009).