Pharmacokinetics and tissue distribution of an orally administered mucoadhesive chitosan-coated amphotericin B-Loaded nanostructured lipid carrier (NLC) in rats

Ling, Janet Tan Sui; Roberts, Clive; Billa, Nashiru

Abstract

© 2019 Informa UK Limited, trading as Taylor & Francis Group. Oral delivery of amphotericin B (AmpB) is desirable because it provides a more patient-friendly mode of administration compared to the current delivery approach akin with the marketed AmpB formulations. The goal of the study was to investigate the pharmacokinetics and tissue distribution of orally administered chitosan-coated AmpB-loaded nanostructured lipid carriers (ChiAmpB NLC) administered to Sprague Dawley rats at a dose of 15 mg/kg. Orally administered ChiAmpB NLC resulted in a two-fold increase in the area under the curve (AUC0-∞) compared to the uncoated AmpB NLC and marketed Amphotret®. This enhanced bioavailability of AmpB suggests prolonged transit and retention of ChiAmpB NLC within the small intestine through mucoadhesion and subsequent absorption by the lymphatic pathway. The results show that mean absorption and residence times (MAT & MRT) were significantly higher from ChiAmpB NLC compared to the other two formulations, attesting to the mucoadhesive effect. The ChiAmpB NLC presented a lower nephrotic accumulation with preferential deposition in liver and spleen. Thus, the limitations of current marketed IV formulations of AmpB are potentially addressed with the ChiAmpB NLC in addition to utilizing this approach for targeting internal organs in visceral leishmaniasis.

Citation

Ling, J. T. S., Roberts, C., & Billa, N. (2019). Pharmacokinetics and tissue distribution of an orally administered mucoadhesive chitosan-coated amphotericin B-Loaded nanostructured lipid carrier (NLC) in rats. Journal of Biomaterials Science, Polymer Edition, 31(2), 141-154. https://doi.org/10.1080/09205063.2019.1680926

• Journal Article Type: Article
• Acceptance Date: Oct 13, 2019
• Online Publication Date: Oct 15, 2019
• Publication Date: Oct 22, 2019
• Deposit Date: Oct 16, 2019
• Publicly Available Date: Oct 16, 2020
• Journal: Journal of Biomaterials Science, Polymer Edition
• Print ISSN: 0920-5063
• Electronic ISSN: 1568-5624
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• Volume: 31
• Issue: 2
• Pages: 141-154
• DOI: https://doi.org/10.1080/09205063.2019.1680926
• Keywords: Amphotericin B, Lymphatic pathway, Mucoadhesion, NLC, Oral delivery, Pharmacokinetics, Tissue distribution
• Public URL: https://nottingham-repository.worktribe.com/output/2845671
• Publisher URL: https://www.tandfonline.com/doi/full/10.1080/09205063.2019.1680926
• Additional Information: Peer Review Statement: The publishing and review policy for this title is described in its Aims & Scope.; Aim & Scope: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=tbsp20; Received: 2019-07-08; Revised: 2019-10-12; Accepted: 2019-10-13; Published: 2019-10-22
• Contract Date: Oct 16, 2019