Biodegradable nanocarriers that have specific stimuli-induced drug release and subsequent degradation would be ideal for a variety of drug delivery applications. The objective of this work is to develop a polymeric nanogel comprised of a biodegradable and non-toxic poly(glutamic acid) backbone, hydrophililic PEG surface and hydrophobic and a glutathione-responsive disulfide cross-linked core. With the appropriate hydrophilic/lipophilic balance, these polymers self-assemble into micellar aggregates in aqueous conditions and are capable of sequestering lipophilic guests. Following addition of a deficient amount of reducing agent DTT, the crosslinked aggregates have enhanced encapsulation stability and stimuli-induced guest release at a cytosol-relevant GSH concentration. Further, poly(glutamic acid) is susceptible to enzyme proteolysis, but with a surface PEG component that reduces non-specific interactions with biological milieu, we expect that in a stable nanogel assembly the degradation would largely occur due to proteolysis in the lysosome following cell-internalization and guest release.

Poly(glutamic acid)-based nanogels for drug delivery applications

251st National Meeting (2016)

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