Lianjun Shi and Cory Berkland. Department of Chemical and Petroleum Engineering, University of Kansas, 2030 Becker Drive, Lawrence, KS 66047
The use of nanoparticles composed of crosslinked water soluble polymers (nanogels) for the encapsulation of active ingredients may be expanded by controlling properties such as size, surface chemistry, degradability, and environmental responsiveness. In particular, nanogels that degrade in response to a reduction in pH have been generating interest because of their potential to be used in the intracellular delivery of biomacromolecules. In this scheme, the rapid acidification that occurs along the endolysosomal pathway is leveraged to disrupt the carrier and trigger payload release prior to fusion with lysosomes. In this study, nanogels were formed by crosslinking poly(N-vinylformamide) (PNVF) with a new acid-labile crosslinker: 2-bis[2,2'-di(N-vinylformamido)ethoxy]propane (BDEP) during the free-radical polymerization of N-vinylformamide (NVF) in a water-in-hexane mini-emulsion. PNVF has been reported to be a non-toxic, biocompatible and highly water-soluble polymer. Nanogel dissolution and release of encapsulated lysozyme occurred much more rapidly at lower pH. This polymer is also attractive because PNVF may be hydrolyzed at high pH to produce polyvinylamine (PVAm) nanogels. PVAm has stable primary amine functionality along its backbone and preliminary data indicate potential value as a gene delivery vector able to condense DNA and enter cells through electrostatic binding. PVAm nanocapsules also showed increased swelling in response to pH decrease. The magnitude of swelling correlated well with the increase in zeta potential of the nanosuspension as pH was lowered. Polyvinyl nanogels crosslinked with an acid-labile crosslinker serve as a unique drug delivery vehicle with multiple functional properties.