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Int. J. Mol. Sci. 2014, 15(1), 342-360; doi:10.3390/ijms15010342

Evaluation of Epirubicin in Thermogelling and Bioadhesive Liquid and Solid Suppository Formulations for Rectal Administration

Department of Biological Sciences and Technology, National University of Tainan, Tainan 700, Taiwan
Department of Chemical and Materials Engineering, Southern Taiwan University of Science and Technology, Tainan 710, Taiwan
Author to whom correspondence should be addressed.
Received: 18 August 2013 / Revised: 16 December 2013 / Accepted: 16 December 2013 / Published: 31 December 2013
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Temperature sensitive Pluronic (Plu) and pH-sensitive polyacrylic acid (PAA) were successfully mixed in different ratios to form in situ gelling formulations for colon cancer therapy. The major formulations were prepared as the liquid and solid suppository dosage forms. Epirubicin (Epi) was chosen as a model anticancer drug. In vitro characterization and in vivo pharmacokinetics and therapeutic efficacy of Epi in six Plu/PAA formulations were evaluated. Our in vitro data indicate that Epi in Plu 14%/PAA 0.75% of both solid and liquid suppositories possess significant cytotoxicity, strong bioadhesive force, long-term appropriate suppository base, sustained release, and high accumulation of Epi in rat rectums. These solid and liquid suppositories were retained in the upper rectum of Sprague-Dawley (SD) rats for at least 12 h. An in vivo pharmacokinetic study using SD rats showed that after rectal administration of solid and liquid suppositories, Epi had greater area under the curve and higher relative bioavailability than in a rectal solution. These solid and liquid suppositories exhibited remarkable inhibition on the tumor growth of CT26 bearing Balb/c mice in vivo. Our findings suggest that in situ thermogelling and mucoadhesive suppositories demonstrate a great potential as colon anticancer delivery systems for protracted release of chemotherapeutic agents.
Keywords: hydrogel; pluronic; polyacrylic acid; epirubicin; colon; suppository hydrogel; pluronic; polyacrylic acid; epirubicin; colon; suppository

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Lo, Y.-L.; Lin, Y.; Lin, H.-R. Evaluation of Epirubicin in Thermogelling and Bioadhesive Liquid and Solid Suppository Formulations for Rectal Administration. Int. J. Mol. Sci. 2014, 15, 342-360.

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