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Spray-Dried Thiolated Chitosan-Coated Sodium Alginate Multilayer Microparticles for Vaginal HIV Microbicide Delivery

  • Research Article
  • Theme: Next Generation Formulation Design: Innovations in Material Selection and Functionality
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Abstract

It is hypothesized that novel thiolated chitosan-coated multilayer microparticles (MPs) with enhanced drug loading are more mucoadhesive than uncoated MPs and safe in vivo for vaginal delivery of topical anti-HIV microbicide. Formulation optimization is achieved through a custom experimental design and the alginate (AG) MPs cores are prepared using the spray drying method. The optimal MPs are then coated with the thiolated chitosan (TCS) using a layer-by-layer method. The morphological analysis, in situ drug payload, in vitro drug release profile, and mucoadhesion potential of the MPs are carried out using scanning electron microscopy, solid-state 31P NMR spectroscopy, UV spectroscopy, fluorescence imaging and periodic acid Schiff method, respectively. The cytotoxicity and preclinical safety of MPs are assessed on human vaginal (VK2/E6E7) and endocervical (End1/E6E7) epithelial cell lines and in female C57BL/6 mice, respectively. The results show that the MPs are successfully formulated with an average diameter ranging from 2 to 3 μm with a drug loading of 7–12% w/w. The drug release profile of these MPs primarily follows the Baker-Lonsdale and Korsmeyer-Peppas models. The MPs exhibit high mucoadhesion (20–50 folds) compared to native AGMPs. The multilayer MPs are noncytotoxic. Histological and immunochemical analysis of the mice genital tract shows neither signs of damage nor inflammatory cell infiltrate. These data highlight the potential use of TCS-coated AG-based multilayer MPs templates for the topical vaginal delivery of anti-HIV/AIDS microbicides.

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Acknowledgments

The work presented was supported by Award Number R01AI087304 from the National Institute of Allergy and Infectious Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. The authors would like to thank Dr. Vladimir Dusevich (Director, Electron Microscopy Facility, School of Dentistry, University of Missouri-Kansas City, MO) for the electron microscopy.

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    Authors and Affiliations

    1. Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, University of Missouri-Kansas City, Kansas City, Missouri, 64108, USA

      Jianing Meng, Vivek Agrahari, Miezan J. Ezoulin, Tao Zhang & Bi-Botti C. Youan

    2. Department of Chemistry, University of Missouri-Kansas City, Kansas City, Missouri, 64110, USA

      Sudhaunshu S. Purohit & Nathan A. Oyler

    3. School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, 64108, USA

      Agostino Molteni & Daniel Dim

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    1. Jianing Meng
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    Correspondence to Bi-Botti C. Youan.

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    Guest Editors: Otilia M. Koo, Panayiotis P. Constantinides, Lavinia M. Lewis, and Joseph Reo

    Jianing Meng and Vivek Agrahari contributed equally to this work.

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    Meng, J., Agrahari, V., Ezoulin, M.J. et al. Spray-Dried Thiolated Chitosan-Coated Sodium Alginate Multilayer Microparticles for Vaginal HIV Microbicide Delivery. AAPS J 19, 692–702 (2017). https://doi.org/10.1208/s12248-016-0007-y

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    • DOI: https://doi.org/10.1208/s12248-016-0007-y

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