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Updated: Oct 20, 2025
Porous Silicon Microparticles for Delivery of siRNA Therapeutics
Published on: January 15, 2015
Engineering mesoporous silica nanoparticles towards oral delivery of vancomycin
John Ndayishimiye1, Yuxue Cao1, Tushar Kumeria2
1School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Brisbane, Queensland 4102, Australia. a.popat@uq.edu.au.
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.
Insights
This study developed silica nanoparticles (SNPs) to improve oral vancomycin (Van) delivery. Large-pore, negatively charged SNPs significantly enhanced Van permeability across epithelial cells, suggesting potential for oral antibiotic administration.
Area of Science:
- Nanotechnology
- Materials Science
- Pharmacology
Background:
- Vancomycin (Van) is crucial for treating MRSA infections but requires parenteral administration due to poor oral bioavailability.
- Limited gastrointestinal (GI) epithelial transport of Van stems from its physicochemical properties.
- Developing oral formulations for Van is essential to reduce treatment costs and improve patient compliance.
Purpose of the Study:
- To engineer silica nanoparticles (SNPs) for enhanced oral delivery of Van.
- To investigate the impact of SNP pore size and surface functionalization on Van loading, release, and epithelial permeability.
- To evaluate the potential of SNPs as a delivery system for Van and other antimicrobial peptides.
Main Methods:
- Synthesized SNPs with varying pore sizes (2 nm, 9 nm) and surface modifications (-NH2, -PO3, -CH3).
- Loaded Van into SNPs, achieving 18-29 wt% loading capacity.
- Assessed Van release kinetics and epithelial permeability using a Caco-2 cell monolayer model.
- Measured tight junction integrity via transepithelial electrical resistance (TEER).
Main Results:
- Van-loaded SNPs demonstrated controlled release profiles, with larger pores and -CH3 functionalization leading to slower release.
- Large-pore, negatively charged SNPs enhanced Van permeability across Caco-2 cells by up to 6-fold.
- SNP-mediated permeation enhancement was attributed to transient, reversible opening of tight junctions, confirmed by TEER decrease.
Conclusions:
- Silica nanoparticles, particularly those with large pores and negative surface charge, show significant potential for enhancing the oral delivery of vancomycin.
- SNP formulation can overcome the poor oral bioavailability of Van by improving its epithelial permeability.
- This approach holds promise for the oral administration of Van and other challenging antimicrobial peptides.
