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Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148
Muhanad Ali1, Miriam E van Gent1, Amy M de Waal1
1Department of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Abstract:
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 °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.
Insights
Formulating synthetic antimicrobial peptide SAAP-148 in PLGA nanoparticles significantly enhances its safety profile and effectiveness against resistant bacteria. This novel approach improves peptide delivery and boosts antimicrobial activity, offering a promising treatment for infections.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Infectious Diseases
Background:
- Synthetic antimicrobial and antibiofilm peptide (SAAP-148) shows potent activity against drug-resistant bacteria.
- SAAP-148's clinical utility is limited by its low selectivity index and poor bioavailability.
- Poly(lactic-co-glycolic) acid (PLGA) nanoparticles offer a platform for controlled peptide delivery.
Purpose of the Study:
- To formulate SAAP-148 into PLGA nanoparticles (SAAP-148 NPs).
- To characterize the physical and functional properties of SAAP-148 NPs.
- To compare the selectivity index and efficacy of SAAP-148 NPs against planktonic and biofilm bacteria with free SAAP-148.
Main Methods:
- SAAP-148 encapsulation into PLGA nanoparticles.
- Physicochemical characterization (size, PDI, surface charge, EE).
- In vitro peptide release studies.
- Antibacterial and antibiofilm assays against resistant *Staphylococcus aureus* and *Acinetobacter baumannii*.
- Cytotoxicity assessments.
- In vitro testing using 3D human skin equivalents (HSEs).
Main Results:
- SAAP-148 NPs exhibited favorable physicochemical properties (94.1 nm size, 0.08 PDI, 1.65 mV charge, 86.7% EE).
- Sustained peptide release observed for up to 21 days.
- Selectivity index increased 10-fold for *S. aureus* and 20-fold for *A. baumannii*.
- Enhanced antibiofilm activity against resistant strains over time.
- SAAP-148 NPs showed promising antibacterial effects in 3D HSE models.
Conclusions:
- PLGA nanoparticle formulation significantly improves SAAP-148's selectivity index and bioavailability.
- SAAP-148 NPs demonstrate sustained release and enhanced antimicrobial and antibiofilm efficacy.
- This nanotechnology-based approach presents a promising strategy for combating antimicrobial resistance infections.
