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Colon-Targeted Delivery of IgY Against Clostridium difficile Toxin A and B by Encapsulation in Chitosan-Ca Pectinate Microbeads

  • Research Article
  • Theme: Recent Trends in the Development of Chitosan-Based Drug Delivery Systems
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Abstract

This study investigated the use of a newly developed chitosan-Ca pectinate microbead formulation for the colon-targeted delivery of anti-A/B toxin immunoglobulin of egg yolk (IgY) to inhibit toxin binding to colon mucosa cells. The effect of the three components (pectinate, calcium chloride, and chitosan) used for the microbead production was examined with the aim of identifying the optimal levels to improve drug encapsulation efficiency, swelling ratio, and cumulative IgY release rate. The optimized IgY-loaded bead component was pectin 5% (w/v), CaCl2 3% (w/v), and chitosan 0.5% (w/v). Formulated beads were spherical with 1.2-mm diameter, and the drug loading was 45%. An in vitro release study revealed that chitosan-Ca pectinate microbeads inhibited IgY release in the upper gastrointestinal tract and significantly improved the site-specific release of IgY in the colon. An in vivo rat study demonstrated that 72.6% of biologically active IgY was released specifically in the colon. These results demonstrated that anti-A/B toxin IgY-loaded chitosan-Ca pectinate oral microbeads improved IgY release behavior in vivo, which could be used as an effective oral delivery platform for the biological treatment of Clostridium difficile infection (CDI).

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ACKNOWLEDGMENTS

This work was supported by the Natural Science Foundation of Shandong (No: ZR2014HM062) and the National Science and Technology Major Project (2013ZX09402201).

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Authors and Affiliations

  1. School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, 264005, China

    Pingping Xing & Kaoxiang Sun

  2. Shandong Luye Pharmaceutical Company, Yantai, 264003, China

    Chuangchuang Dong, Hong Liu, Yan Cheng, Junbo Sun, Dalei Li, Min Li & Dongxiao Feng

  3. School of Pharmaceutical Sciences, Shandong Binzhou Medical University, Yantai, 264003, China

    Yanan Shi & Dongxiao Feng

Authors
  1. Pingping Xing
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  2. Yanan Shi
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  3. Chuangchuang Dong
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  4. Hong Liu
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  5. Yan Cheng
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  6. Junbo Sun
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  8. Min Li
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  9. Kaoxiang Sun
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  10. Dongxiao Feng
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Corresponding authors

Correspondence to Kaoxiang Sun or Dongxiao Feng.

Ethics declarations

This study was performed in accordance with the recommendations of the US Department of Health and Human Services for the care and use of laboratory animals. All animals were exposed to CO2 for anesthesia before being sacrificed, and the protocols were approved by the Animal Ethics Committee of Shandong Binzhou Medical University (permit number: 2014–05).

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The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

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Guest Editors: Claudio Salomon, Francisco Goycoolea, and Bruno Moerschbacher

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Xing, P., Shi, Y., Dong, C. et al. Colon-Targeted Delivery of IgY Against Clostridium difficile Toxin A and B by Encapsulation in Chitosan-Ca Pectinate Microbeads. AAPS PharmSciTech 18, 1095–1103 (2017). https://doi.org/10.1208/s12249-016-0656-2

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  • DOI: https://doi.org/10.1208/s12249-016-0656-2

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