Oral administration of hydrophobic and poorly intestinal epithelium-permeable drugs is a significant challenge. Herein, we report a new strategy to overcome this problem by using novel, pH-responsive, and membrane-active nanogels as drug carriers. Prepared by simple physical cross-linking of amphiphilic pseudopeptidic polymers with pH-controlled membrane-activity, the size and hydrophobicity-hydrophilicity balance of the nanogels could be well-tuned. Furthermore, the amphiphilic nanogels could release hydrophobic payloads and destabilize cell membranes at duodenum and jejunum pH 5.0-6.0, which suggests their great potential for intestinal drug delivery.
Keywords: hydrophobic drug; membrane-active; nanogel; oral delivery; pH-responsive.