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The intestinal absorption of hydrophilic drugs and macromolecular drugs is generally limited by their poor membrane permeability characteristics in the intestine. Therefore, absorption enhancers were usually adopted for improving the intestinal absorption of these poorly absorbable drugs. However, conventional absorption enhancers were generally more effective in the large intestine rather than the small intestine and absorption enhancers with high effectiveness in the small intestine is highly desirable. Based on the background, we focused on polyamidoamine (PAMAM) dendrimers as novel absorption enhancers and effects of PAMAM dendrimers on the intestinal absorption of poorly absorbable drugs were examined by an in situ closed loop method in rats. The absorption of 5(6)-carboxyfluorescein (CF), fluorescein isothiocyanate-dextran with an average molecular weight of 4000 (FD4) and calcitonin from the rat small intestine was significantly enhanced in the presence of PAMAM dendrimers. However, PAMAM dendrimers had almost no absorption enhancing effect on the small intestinal absorption of macromolecular drugs including fluorescein isothiocyanate-dextran with an average molecular weight of 10000 (FD10) and insulin. Furthermore, we evaluated the intestinal membrane damage with or without PAMAM dendrimers. PAMAM dendrimers at concentrations of 0.05% (w/v) and 0.1% (w/v) did not increase the activities of lactate dehydrogenase (LDH) and amounts of protein in the intestine. These findings suggested that PAMAM dendrimers at lower concentrations might be potential and safe absorption enhancers for improving absorption of poorly absorbable drugs from the small intestine.

Improvement of Intestinal Absorption of Poorly Absorbable Drugs by Polyamidoamine (PAMAM) Dendrimers as Novel Absorption Enhancers