Endogenous and exogenous control of polymers for spatiotemporally defined drug delivery

Abstract

Polymeric ‘smart drug delivery systems’ respond to external and environmental stimuli to modulate drug release at the right time and in the right place. Here I present several polymer systems to overcome challenges in spatiotemporal control of drug delivery. First, a novel acid-labile liquid polymer responsive to endogenous pH conditions was synthesized and characterized for releasing poorly soluble drugs as an injectable depot, a photo-crosslinked implantable matrix, temporarily stable nanodroplets and stable nanogels. Second, two acid-labile biodegradable liquid polymers were investigated for pH-responsive intracellular delivery of the immunomodulator R848 (or Resiquimod), a poorly soluble adjuvant for a melanoma vaccine. Third, nanodroplets of one of the liquid polymers were embedded in mucoadhesive wafers and were evaluated for spatially defined drug delivery to engineered tissues. Lastly, exogenously controlled drug release was demonstrated using a novel gold-coated hydrogel and focused ultrasound. Together, these studies have presented new biomaterial systems as versatile tools for controlled drug delivery with potential applications in immunotherapy and tissue engineering.