4.7 Article

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

期刊

PHARMACEUTICS
卷 14, 期 5, 页码 -

出版社

MDPI
DOI: 10.3390/pharmaceutics14050986

关键词

antimicrobial peptides; antimicrobial resistance; mesoporous silica nanoparticles; sortase A inhibitors; synergy

资金

  1. University of Queensland (UQ) School of Pharmacy
  2. Faculty of Health and Behavioural Sciences (HaBS)
  3. Shaqra University, Saudi Arabia
  4. Metagenics
  5. Career Development Fellowship from the Australian National Health and Medical Research Council (NHMRC) [GNT1146627]
  6. Early Career Fellowship from the Australian National Health and Medical Research Council (NHMRC) [GNT1071796]

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This study aimed to develop synergistic therapies to treat superbug infections through the encapsulation of sortase A inhibitors into mesoporous silica nanoparticles. The results demonstrated that this encapsulation method significantly improved the solubility of the inhibitors and showed synergistic effects with antimicrobial peptides.
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.

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