Synthesis and characterization of pH-responsive nanoscale hydrogels for oral delivery of hydrophobic therapeutics

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Abstract

pH-responsive, polyanionic nanoscale hydrogels were developed for the oral delivery of hydrophobic therapeutics, such as common chemotherapeutic agents. Nanoscale hydrogels were designed to overcome physicochemical and biological barriers associated with oral delivery of hydrophobic therapeutics such as low solubility and poor permeability due to P-glycoprotein related drug efflux. Synthesis of these nanoscale materials was achieved by a robust photoemulsion polymerization method. By varying hydrophobic monomer components, four formulations were synthesized and screened for optimal physicochemical properties and in vitro biocompatibility. All of the responsive nanoscale hydrogels were capable of undergoing a pH-dependent transition in size. Depending on the selection of the hydrophobic monomer, the sizes of the nanoparticles vary widely from 120 nm to about 500 nm at pH 7.4. Polymer composition was verified using Fourier transform infrared spectroscopy and 1H-nuclear magnetic resonance spectroscopy. Polymer biocompatibility was assessed in vitro with an intestinal epithelial cell model. All formulations were found to have no appreciable cytotoxicity, defined as greater than 80% viability after polymer incubation. We demonstrate that these nanoscale hydrogels possess desirable physicochemical properties and exhibit agreeable in vitro biocompatibility for oral delivery applications.

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