Ph-Responsive Nanogels from Bioinspired Comb-Like Polymers with Hydrophobic Grafts for Effective Oral Delivery

This study explores the development of pH-responsive nanogels using bioinspired comb-like anionic polymers for effective oral drug delivery. By grafting alkylamines of varying chain lengths and densities onto a biodegradable poly(L-lysine isophthalamide) backbone, researchers created nanogels capable of loading the chemotherapeutic agent camptothecin. The optimal formulation, with 30% C₁₄ grafting, demonstrated high drug-loading capacity, stability, and protection in acidic conditions, with only 7 ± 5% release at pH 1.2 over 24 hours, while allowing rapid release at pH 7.4 (78 ± 2% within 24 hours). These nanogels significantly improved cellular uptake and cytotoxicity against colorectal carcinoma cells, highlighting the importance of hydrophobic modification in designing effective oral nanocarriers for intestinal disease treatment.