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Improved intestinal absorption of water-soluble drugs by acetylation of G2 PAMAM dendrimer nanocomplexes in rat

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Abstract

In search of an effective and less toxic absorption enhancer, we synthesized primary amine acetylation of generation 2 polyamidoamine (G2 PAMAM) dendrimer (Ac-G2) by the reaction of G2 PAMAM dendrimer with acetic anhydride, and evaluated the effects of Ac-G2 on the intestinal absorption of poorly absorbable water-soluble drugs using an in situ closed-loop method in rats. The results indicated that Ac50-G2 had a greatest absorption enhancing effect for 5(6)-carboxyfluorescein (CF) in various acetylation levels of G2 PAMAM dendrimers. Ac50-G2 with various concentrations (0.1–1.0%, w/v) could significantly improve the intestinal absorption of alendronate, CF, and fluorescein isothiocyanate-labeled dextrans (FD4), although they did not enhance the absorption of macromolecular drug of FD10, and the absorption enhancement effect of Ac50-G2 was concentration-dependent. Furthermore, we examined the intestinal membrane damage with or without Ac50-G2. The results displayed Ac50-G2 at lower concentrations (0.1–0.5%, w/v) did not cause any observed toxic effect to the intestinal membranes. These findings suggested Ac50-G2 at lower concentrations (below 0.5%, w/v) might be promising as an effective and safe absorption enhancers to promote the intestinal absorption of poorly absorbable drugs.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81260484) and the Program of Guangxi Provincial Natural Science Foundation of China (2013GXNSFAA019226).

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Authors and Affiliations

  1. College of Pharmacy|, Guilin Medical University, Guilin,, 541004, China

    Chengyun Yan

  2. First Affiliated Hospital of Jiamusi University, Jiamusi University, Jiamusi, 154000, China

    Chengyun Yan, Jiwei Gu & Hongying Jing

  3. College of Pharmacy, Jiamusi University, Jiamusi, 154000, China

    Yuguang Lv & Weiguo Shi

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  1. Chengyun Yan
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Correspondence to Chengyun Yan.

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Yan, C., Gu, J., Lv, Y. et al. Improved intestinal absorption of water-soluble drugs by acetylation of G2 PAMAM dendrimer nanocomplexes in rat. Drug Deliv. and Transl. Res. 7, 408–415 (2017). https://doi.org/10.1007/s13346-017-0373-8

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