5β-Cholanic Acid/Glycol Chitosan Self-Assembled Nanoparticles (5β-CHA/GC-NPs) for Enhancing the Absorption of FDs and Insulin by Rat Intestinal Membranes.

Abstract

The absorption-enhancing effects of glycol chitosan modified by 5β-cholanic acid nanoparticles (5β-CHA/GC-NPs) on a drug with poor absorption in the intestine were studied by the method of in situ closed loop. We chose fluorescein isothiocyanate-labeled dextrans (FDs) and insulin as the model drugs. 5β-CHA/GC-NPs loaded to different drugs were prepared by the dialysis method, and the physicochemical characteristics and in vitro release profiles of nanoparticles were also estimated. The results showed that 5β-CHA/GC-NPs markedly increased the absorption of insulin and FDs in the jejunum, ileum, and colon. The ratios of absorption for all the drugs in the jejunum were higher than those in the ileum and colon. In addition, the enhancing effect of 5β-CHA/GC-NPs for the absorption of FDs from the jejunum was decreased with increasing molecular weights. In the toxicity test, 5β-CHA/GC-NPs did not significantly increase the release of protein and the activities of LDH, indicating that the nanoparticles did not cause any membrane damage to the intestine. These findings suggested that 5β-CHA/GC-NPs were safe and useful carriers for enhancing the absorption of the drug with poor absorption by intestinal membranes.