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Development of Amphotericin B-Loaded Cubosomes Through the SolEmuls Technology for Enhancing the Oral Bioavailability

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Abstract

The oral administration of amphotericin B (AmB) has the major drawback of poor bioavailability. The aim of this work was to evaluate the potential of AmB-loaded cubosomes as an oral formulation with improved bioavailability. This manuscript firstly developed AmB-loaded cubosomes by using the SolEmuls technology. The encapsulation efficiency, the in vitro release, and stability studies in simulated gastrointestinal fluid were used to evaluate AmB-loaded cubosomes. The acute nephrotoxicity, bioavailability, and tissue distribution study of AmB-loaded cubosomes were assayed upon oral administration to rats. SAXS and cryo-TEM exhibited AmB-loaded cubosomes as a bicontinuous cubic liquid crystalline phase with Pn3m geometry. The encapsulation efficiency and the results of in vitro release and stability studies in simulated gastrointestinal fluid further demonstrated that AmB was successfully encapsulated in cubosomes. AmB-loaded cubosomal formulation orally administrated in rats did not show nephrotoxicity and its relative bioavailability was approximately 285% as compared to Fungizone®. The AmB-loaded cubosomal formulation presented an effective potential approach for enhancing the oral bioavailability of AmB.

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Acknowledgements

The authors are grateful to BASF company, Germany, for generous gift samples of Poloxamer 407. The authors are grateful to NCPC Company, China, for generous gift samples of Fungizone®. We thank National Basic Research Program of China (No 81173002) for the financial support. This work was also supported in part by National Key Technology R&D Program (NO:2012BAI35B02) and by Ministry of Science and Technology of China (Projects of International Cooperation and Exchanges; NO2008DFA31080).

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People’s Republic of China

    Zhiwen Yang, Yinhe Tan, Meiwan Chen, Linghui Dian, Ziyun Shan, Xinsheng Peng & Chuanbin Wu

  2. Department of Gastroenterology, Songjiang Hospital Affiliated the First People’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China

    Zhiwen Yang

  3. Guangdong Research Center for Drug Delivery Systems, Guangzhou, People’s Republic of China

    Chuanbin Wu

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  1. Zhiwen Yang
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  2. Yinhe Tan
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Correspondence to Chuanbin Wu.

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Yang, Z., Tan, Y., Chen, M. et al. Development of Amphotericin B-Loaded Cubosomes Through the SolEmuls Technology for Enhancing the Oral Bioavailability. AAPS PharmSciTech 13, 1483–1491 (2012). https://doi.org/10.1208/s12249-012-9876-2

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