Enhancing the cellular uptake and antibacterial activity of rifampicin through encapsulation in mesoporous silica nanoparticles
Journal article, 2020

An urgent demand exists for the development of novel delivery systems that efficiently transport antibacterial agents across cellular membranes for the eradication of intracellular pathogens. In this study, the clinically relevant poorly water-soluble antibiotic, rifampicin, was confined within mesoporous silica nanoparticles (MSN) to investigate their ability to serve as an efficacious nanocarrier system against small colony variants of Staphylococcus aureus (SCV S. aureus) hosted within Caco-2 cells. The surface chemistry and particle size of MSN were varied through modifications during synthesis, where 40 nm particles with high silanol group densities promoted enhanced cellular uptake. Extensive biophysical analysis was performed, using quartz crystal microbalance with dissipation (QCM-D) and total internal reflection fluorescence (TIRF) microscopy, to elucidate the mechanism of MSN adsorption onto semi-native supported lipid bilayers (snSLB) and, thus, uncover potential cellular uptake mechanisms of MSN into Caco-2 cells. Such studies revealed that MSN with reduced silanol group densities were prone to greater particle aggregation on snSLB, which was expected to restrict endocytosis. MSN adsorption and uptake into Caco-2 cells correlated well with antibacterial efficacy against SCV S. aureus, with 40 nm hydrophilic particles triggering a ~2.5-log greater reduction in colony forming units, compared to the pure rifampicin. Thus, this study provides evidence for the potential to design silica nanocarrier systems with controlled surface chemistries that can be used to re-sensitise intracellular bacteria to antibiotics by delivering them to the site of infection.


Staphylococcus aureus





Small colony variants

Total internal reflection

Mesoporous silica

Fluorescence microscopy


Paul Joyce

Chalmers, Physics, Biological Physics

Hanna Ulmefors

University of South Australia

Sajedehsadat Maghrebi

University of South Australia

Santhni Subramaniam

University of South Australia

Anthony Wignall

University of South Australia

Silver Jõemetsa

Chalmers, Physics, Biological Physics

Fredrik Höök

Nano and Biophysics

Clive A. Prestidge

University of South Australia


20794991 (eISSN)

Vol. 10 4 815

Design of porus lipid-silica nanocarriers for local enzyme-controlled drug administration

ÅForsk, 2016-07-01 -- 2019-12-31.

Subject Categories

Physical Chemistry

Materials Chemistry

Other Chemistry Topics



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