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Lactoferrin-Loaded Alginate Microparticles to Target Clostridioides difficile Infection

Braim, Shwana; Śpiewakb, Klaudyna; Brindell, Malgorzata; Heeg, Daniela; Alexander, Cameron; Monaghan, Tanya

Lactoferrin-Loaded Alginate Microparticles to Target Clostridioides difficile Infection Thumbnail


Authors

Shwana Braim

Klaudyna Śpiewakb

Malgorzata Brindell

Daniela Heeg

TANYA MONAGHAN Tanya.Monaghan@nottingham.ac.uk
Clinical Associate Professor in Luminal Gastroenterology



Abstract

Some forms of bovine lactoferrin (bLf) are effective in delaying Clostridioides difficile growth and preventing toxin production. However, therapeutic use of bLf may be limited by protein stability issues. The objective of this study was to prepare and evaluate colon-targeted, pH-triggered alginate microparticles loaded with bioactive bLf and to evaluate their anti-C. difficile defence properties in vitro. Different forms of metal-bound bLf were encapsulated in alginate microparticles using an emulsification/internal gelation method. The microparticles were coated with chitosan to control protein release. In vitro drug release studies were conducted in pH-simulated gastrointestinal conditions to investigate the release kinetics of encapsulated protein. No significant release of metal-bound bLf was observed at acidic pH; however, on reaching simulated colonic pH, most of the encapsulated lactoferrin was released. The application of bLf (5mg/mL) delivered from alginate microparticles to human intestinal epithelial cells (hIECs) significantly reduced the cytotoxic effects of toxins A and B as well as bacterial supernatant on Caco-2 and Vero cells, respectively. These results are the first to suggest that alginate-bLf microparticles show protective effects against C. difficile toxin-mediated epithelial damage and impairment of barrier function in hIECs. The future potential of lactoferrin-loaded alginate microparticles against C. difficile deserves further study.

Journal Article Type Article
Acceptance Date Feb 25, 2019
Online Publication Date Mar 6, 2019
Publication Date Jul 1, 2019
Deposit Date Feb 27, 2019
Publicly Available Date Mar 7, 2020
Journal Journal of Pharmaceutical Sciences
Print ISSN 0022-3549
Electronic ISSN 1520-6017
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 108
Issue 7
Pages 2438-2446
DOI https://doi.org/10.1016/j.xphs.2019.02.025
Keywords Lactoferrin, alginate microparticles, Clostridioides difficile, targeted drug delivery, gastrointestinal tract
Public URL https://nottingham-repository.worktribe.com/output/1587965
Publisher URL https://www.sciencedirect.com/science/article/pii/S0022354919301431