Local delivery of immune modulating molecules to immune cell populations while omitting systemic inflammatory toxicity still remains challenging, especially for highly polar immune modulating drugs. In order to alter their pharmacokinetic behavior, nano-sized carrier systems could suppress systemic drug exposure and facilitate local delivery to phagocytosing immune cells. However, as many highly polar immune modulators are exclusively soluble in water, strategies have to be developed to immobilize them to polar drug delivery systems. Usually, the reactive ester approach is a versatile tool to generate core-crosslinked micellar nanogels via self-assembled amphiphilic reactive ester block copolymers. However, under aqueous conditions the half-life of many reactive esters is too short to facilitate covalent conjugation of highly polar molecules and the fabrication of nanogels in water. Therefore, we developed novel reactive precursor polymers based on squaric ester amide side groups, which are less prone to hydrolysis and allow amine conjugation reactions under aqueous conditions with high yield. The formation of polymeric squaric bisamides can be monitored by UV-vis spectroscopy, while the conversion with acid-degradable bisamine crosslinkers assures the formation of core-crosslinked micellar nanogels that disassemble under endosomal pH conditions. During the fabrication process also highly polar drugs with single amine functionalities can further be locked onto the carrier system and, thus, guarantee covalent drug delivery strategies for highly polar immune modulators through pH-degradable nanogels.

Delivering highly polar immune modulators by pH-degradable nanogels derived from squaric ester amide-based precursor polymers

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.