Formulation and Biological Evaluation of Mesoporous Silica Nanoparticles Loaded with Combinations of Sortase A Inhibitors and Antimicrobial Peptides

Abstract

This study aimed to develop synergistic therapies to treat superbug infections through the encapsulation of sortase A inhibitors (SrtAIs; trans-chalcone (TC), curcumin (CUR), quercetin (QC), or berberine chloride (BR)) into MCM-41 mesoporous silica nanoparticles (MSNs) or a phosphonate-modified analogue (MCM-41-PO3−) to overcome their poor aqueous solubility. A resazurin-modified minimum inhibitory concentration (MIC) and checkerboard assays, to measure SrtAI synergy in combination with leading antimicrobial peptides (AMPs; pexiganan (PEX), indolicidin (INDO), and [I5, R8] mastoparan (MASTO)), were determined against methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The results demonstrated that the MCM-41 and MCM-41-PO3− formulations significantly improved the aqueous solubility of each SrtAI. The MICs for SrtAI/MCM-41-PO3− formulations were lower compared to the SrtAI/MCM-41 formulations against tested bacterial strains, except for the cases of BR/MCM-41 and QC/MCM-41 against P. aeruginosa. Furthermore, the following combinations demonstrated synergy: PEX with TC/MCM-41 (against all strains) or TC/MCM-41-PO3− (against all strains except P. aeruginosa); PEX with BR/MCM-41 or BR/MCM-41-PO3− (against MSSA and MRSA); INDO with QC/MCM-41 or QC/MCM-41-PO3− (against MRSA); and MASTO with CUR/MCM-41 (against E. coli). These combinations also reduced each components’ toxicity against human embryonic kidney cells. In conclusion, MCM-41 MSNs provide a platform to enhance SrtAI solubility and demonstrated antimicrobial synergy with AMPs and reduced toxicity, providing novel superbug treatment opportunities.

Understanding Fenofibrate Release from Bare and Modified Mesoporous Silica Nanoparticles

“…Among these, there have been several attempts reported in the literature to explore FNB in the amorphous state by incorporating it in silica matrices [ 13 , 14 ]. These drug carriers present significant low cytotoxicity [ 15 , 16 , 17 ] and a high surface area, allowing for a high dispersion of the loaded compound. However, the crystallization tendency has not been totally suppressed in silica-based FNB formulations [ 18 , 19 ].…”

Influence of Pore Size and Surface Functionalization of Mesoporous Silica Nanoparticles on the Solubility and Antioxidant Activity of Confined Coenzyme Q10

“…This surface charge effect on changing Q10 solubility is present irrespective of the shape and size of MSN as it is observed in both MCM-41 and SBA-15. Furthermore, the phosphonate-modified particles, which are highly negatively charged, reveal enhanced solubility profile, that could be due to better colloidal stability and improved hydrophilicity provided by phosphonate groups, which is in agreement with low particle agglomeration as observed from TEM (Figure ) and PDI values (MCM-41-PO 3 : 0.25 vs MCM-41-NH 2 : 0.45, respectively). , While comparing the solubility profiles of Q10 among the phosphonate-modified particles, MCM-41-PO 3 -Q10 showed significantly higher solubility (2-folds) than SBA-15-PO 3 -Q10, which may be attributed to a combination of particle size and charge distribution effects. However, the pristine particle SBA-15-Q10 showed higher drug solubility than MCM-41-Q10 although the pore size of MCM-41 is smaller and the surface area is higher.…”

The application of mesoporous silica nanoparticles as a drug delivery vehicle in oral disease treatment

“…Naturally derived compounds with poor water solubility are classified as sortase A inhibitors (SrtAIs), including quercetin (QC) and berberine chloride (BR). With the help of MSNs, SrtAI’s solubility can be increased, opening up new therapy options for superbugs with less hazardous side effects ( Alharthi et al., 2022 ). When drugs are combined with MSNs, the antibacterial effect may be enhanced, the drug’s release time may be prolonged, the inherent cytotoxicity may be eliminated, and bacterial resistance may be addressed with great physiochemical performance.…”