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Novel pH-sensitive lipid–polymer composite microspheres of 10-hydroxycamptothecin exhibiting colon-specific biodistribution and reduced systemic absorption

Authors

  • Li Gan,

    1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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    • Li Gan and Yi-Ping Gao contributed equally to this work.

  • Yi-Ping Gao,

    1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
    2. Xuhui District Central Hospital, Shanghai 200031, China
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    • Li Gan and Yi-Ping Gao contributed equally to this work.

  • Chun-Liu Zhu,

    1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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  • Xin-Xin Zhang,

    1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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  • Yong Gan

    Corresponding author
    1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
    • Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Telephone: +86-21-2023-1975; Fax: +86-21-2023-1000/1425
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Abstract

Novel lipid–polymer composite microspheres (LP-MS) were prepared by combining pH-sensitive polymer Eudragit S100 with solid lipid Compritol 888 ATO for colonic delivery of 10-hydroxycamptothecin (HCPT), and pH-dependent controlled drug release has been achieved. The colon-specific biodistribution and uptake by the mucosal tissue were examined using coumarin-6-marked LP-MS. It is proved that good in vitro–in vivo relationship has been achieved, with more drugs being delivered to colon and a higher drug level was maintained for a long period. Moreover, in vivo bioavailability of LP-MS was evaluated with conventional enteric microspheres (enteric MS) as reference. After administration of LP-MS, systemic absorption of HCPT was greatly reduced, with area under the curve from 0 to 24h (AUC0–24 h, 2.186 ± 0.27) being significantly lower than that of enteric MS group (6.352 ± 0.696). In conclusion, the novel pH-sensitive LP-MS has potential for colon-specific drug delivery. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1752–1759, 2013

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