Mucoadhesive chitosan-coated nanostructured lipid carriers for oral delivery of amphotericin B

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

Abstract

This study describes the properties of an amphotericin B-containing mucoadhesive nanostructured lipid carrier (NLC), with the intent to maximize uptake within the gastrointestinal tract. We have reported previously that lipid nanoparticles can significantly improve the oral bioavailability of amphotericin B (AmpB). On the other hand, the aggregation state of AmpB within the NLC has been ascribed to some of the side effects resulting from IV administration. In the undissolved state, AmpB (UAmpB) exhibited the safer monomeric conformation in contrast to AmpB in the dissolved state (DAmpB), which was aggregated. Chitosan-coated NLC (ChiAmpB NLC) presented a slightly slower AmpB release profile as compared to the uncoated formulation, achieving 26.1 % release in 5 hours. Furthermore, the ChiAmpB NLC formulation appeared to prevent the expulsion of AmpB upon exposure to simulated gastrointestinal pH media, whereby up to 63.9 % of AmpB was retained in the NLC compared to 56.1 % in the uncoated formulation. The ChiAmpB NLC demonstrated mucoadhesive properties in pH 5.8 and 6.8. Thus, the ChiAmpB NLC formulation is well-primed for pharmacokinetic studies to investigate whether delayed gastrointestinal transit may be exploited to improve the systemic bioavailability of AmpB, whilst simultaneously addressing the side-effect concerns of AmpB.

• Journal Article Type: Article
• Acceptance Date: Aug 19, 2018
• Online Publication Date: Sep 26, 2018
• Publication Date: Sep 26, 2018
• Deposit Date: Aug 22, 2018
• Publicly Available Date: Sep 27, 2019
• Journal: Pharmaceutical Development and Technology
• Print ISSN: 1083-7450
• Electronic ISSN: 1097-9867
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• Volume: 24
• Issue: 4
• Pages: 504-512
• DOI: https://doi.org/10.1080/10837450.2018.1515225
• Keywords: amphotericin B, nanostructured lipid carriers, oral, mucoadhesion, aggregation states
• Public URL: https://nottingham-repository.worktribe.com/output/1043232
• Publisher URL: https://www.tandfonline.com/doi/abs/10.1080/10837450.2018.1515225?journalCode=iphd20
• 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=iphd20; Received: 2018-05-21; Revised: 2018-08-18; Accepted: 2018-08-19; Published: 2018-09-26