Enhancing the Cellular Uptake and Antibacterial Activity of Rifampicin through Encapsulation in Mesoporous Silica Nanoparticles

Abstract

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.

Oral Drug Delivery Systems Based on Ordered Mesoporous Silica Nanoparticles for Modulating the Release of Aprepitant

“…Importantly, this effect does not seem to be dose-dependent, and could be attributed to mechanical obstruction of the materials to cell proliferation potential [ 34 , 35 ]. The results obtained in the current study are in good agreement with previous studies where ordered mesoporous silica did not exhibit any toxicity when tested in Caco-2 cell lines [ 36 , 37 , 38 ].…”

“…Finally, the cell viability study of Caco-2 cells incubated with MCM-41 and MCM-48 in the presence and absence of aprepitant showed that both materials do not present any significant toxicity in vitro, in good agreement with previously reported studies on similar materials [ 36 , 37 , 38 ]. All above results confirm that ordered mesoporous silica nanoparticles such as MCM-41 and MCM-48 provide a good platform for the development of effective aprepitant carriers.…”

“…Both MCM-41 and MCM-48 particles exhibited spherical morphology (diameters 80–150 nm) and pore sizes between 3–4 nm, which is typical for these materials [ 1 , 30 , 36 , 38 , 39 ]. The pore network structure of the particles was verified by pXRD analysis and the results were in good agreement with the literature [ 17 , 22 , 23 ].…”

Delivery by Dendritic Mesoporous Silica Nanoparticles Enhances the Antimicrobial Activity of a Napsin‐Derived Peptide Against Intracellular Mycobacterium tuberculosis

“…Among the class of inorganic nanomaterials mesoporous silica nanoparticles (MSN) are a promising drug delivery system for small molecule as well as protein/peptide and DNA/RNA based drugs. [21][22][23] The most outstanding properties of this class of material relevant for the application as a drug vector include the tunability in particle size, morphology and charge, various geometries and dimensions of the porous network and in most cases high biocompatibility and tunable biodegradability. Several studies underline that MSN have a great potential as drug delivery system in tuberculosis therapy.…”

Recent Advances Toward the Use of Mesoporous Silica Nanoparticles for the Treatment of Bacterial Infections

“…In another interesting set of contributions, Subramaniam et al and Joyce et al evaluated the behavior between MSNs with different particle sizes 41 and surface functionalization 42 to be tested on S. aureus intracellular infections. In these contributions the authors employed Hiroshima mesoporous materials (HMM) with sizes in the range of 40–100 nm and rifampicin as antibiotic cargo.…”