4.7 Article

Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148

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Publisher

MDPI
DOI: 10.3390/ijms24032867

Keywords

antimicrobial peptide; skin infection; PLGA; nanoparticle; drug delivery system; bacterial; biofilm

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The formulation of SAAP-148 in PLGA nanoparticles improves its selectivity index and enables sustained release of the peptide. The nanoparticles exhibit favorable physiochemical properties and demonstrate increased activity against antimicrobial resistant bacteria and biofilms over time. This suggests that SAAP-148 nanoparticles have promising potential as a treatment for bacterial infections.
Synthetic antimicrobial and antibiofilm peptide (SAAP-148) commits significant antimicrobial activities against antimicrobial resistant (AMR) planktonic bacteria and biofilms. However, SAAP-148 is limited by its low selectivity index, i.e., ratio between cytotoxicity and antimicrobial activity, as well as its bioavailability at infection sites. We hypothesized that formulation of SAAP-148 in PLGA nanoparticles (SAAP-148 NPs) improves the selectivity index due to the sustained local release of the peptide. The aim of this study was to investigate the physical and functional characteristics of SAAP-148 NPs and to compare the selectivity index of the formulated peptide with that of the peptide in solution. SAAP-148 NPs displayed favorable physiochemical properties [size = 94.1 +/- 23 nm, polydispersity index (PDI) = 0.08 +/- 0.1, surface charge = 1.65 +/- 0.1 mV, and encapsulation efficiency (EE) = 86.7 +/- 0.3%] and sustained release of peptide for up to 21 days in PBS at 37 degrees C. The antibacterial and cytotoxicity studies showed that the selectivity index for SAAP-148 NPs was drastically increased, by 10-fold, regarding AMR Staphylococcus aureus and 20-fold regarding AMR Acinetobacter baumannii after 4 h. Interestingly, the antibiofilm activity of SAAP-148 NPs against AMR S. aureus and A. baumannii gradually increased overtime, suggesting a dose-effect relationship based on the peptide's in vitro release profile. Using 3D human skin equivalents (HSEs), dual drug SAAP-148 NPs and the novel antibiotic halicin NPs provided a stronger antibacterial response against planktonic and cell-associated bacteria than SAAP-148 NPs but not halicin NPs after 24 h. Confocal laser scanning microscopy revealed the presence of SAAP-148 NPs on the top layers of the skin models in close proximity to AMR S. aureus at 24 h. Overall, SAAP-148 NPs present a promising yet challenging approach for further development as treatment against bacterial infections.

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