Issue 35, 2021

Engineering mesoporous silica nanoparticles towards oral delivery of vancomycin

Abstract

Vancomycin (Van) is a key antibiotic of choice for the treatment of systemic methicillin resistant Staphylococcus aureus (MRSA) infections. However, due to its poor membrane permeability, it is administered parenterally, adding to the cost and effort of treatment. The poor oral bioavailability of Van is mainly due to its physico-chemical properties that limit its paracellular and transcellular transport across gastrointestinal (GI) epithelium. Herein we report the development of silica nanoparticles (SNPs)-based formulations that are able to enhance the epithelial permeability of Van. We synthesized SNPs of different pore sizes (2 nm and 9 nm) and modified their surface charge and polarity by attaching different functional groups (–NH2, –PO3, and –CH3). Van was loaded within these SNPs at a loading capacity in the range of ca. 18–29 wt%. The Van-loaded SNPs exhibited a controlled release behaviour when compared to un-encapsulated Van which showed rapid release due to its hydrophilic nature. Among Van-loaded SNPs, SNPs with large pores showed a prolonged release compared to SNPs with small pores while SNPs functionalised with -CH3 groups exhibited a slowest release among the functionalised SNPs. Importantly, Van-loaded SNPs, especially the large pore SNPs with negative charge, enhanced the permeability of Van across an epithelial cell monolayer (Caco-2 cell model) by up to 6-fold, with Papp values up to 1.716 × 10−5 cm s−1 (vs. 0.304 × 10−5 cm s−1 for un-encapsulated Van) after 3 h. The enhancement was dependent on both the type of SNPs and their surface functionalisation. The permeation enhancing effect of SNPs was due to its ability to transiently open the tight junctions measured by decrease in transepithelial resistance (TEER) which was reversible after 3 h. All in all, our data highlights the potential of SNPs (especially SNPs with large pores) for oral delivery of Van or other antimicrobial peptides.

Graphical abstract: Engineering mesoporous silica nanoparticles towards oral delivery of vancomycin

Supplementary files

Article information

Article type
Paper
Submitted
26 jun 2021
Accepted
09 ago 2021
First published
09 ago 2021

J. Mater. Chem. B, 2021,9, 7145-7166

Engineering mesoporous silica nanoparticles towards oral delivery of vancomycin

J. Ndayishimiye, Y. Cao, T. Kumeria, M. A. T. Blaskovich, J. R. Falconer and A. Popat, J. Mater. Chem. B, 2021, 9, 7145 DOI: 10.1039/D1TB01430G

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements