Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148
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 w...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2867 |
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| author | Muhanad Ali Miriam E. van Gent Amy M. de Waal Bjorn R. van Doodewaerd Erik Bos Roman I. Koning Robert A. Cordfunke Jan Wouter Drijfhout Peter H. Nibbering |
| author_facet | Muhanad Ali Miriam E. van Gent Amy M. de Waal Bjorn R. van Doodewaerd Erik Bos Roman I. Koning Robert A. Cordfunke Jan Wouter Drijfhout Peter H. Nibbering |
| author_sort | Muhanad Ali |
| collection | DOAJ |
| description | 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 <i>Staphylococcus aureus</i> and 20-fold regarding AMR <i>Acinetobacter baumannii</i> after 4 h. Interestingly, the antibiofilm activity of SAAP-148 NPs against AMR <i>S. aureus</i> and <i>A. baumannii</i> 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 <i>S. aureus</i> at 24 h. Overall, SAAP-148 NPs present a promising yet challenging approach for further development as treatment against bacterial infections. |
| first_indexed | 2024-03-11T09:39:57Z |
| format | Article |
| id | doaj.art-766b77927e0e4ada8907f81ee317660a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:39:57Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-766b77927e0e4ada8907f81ee317660a2023-11-16T17:03:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01243286710.3390/ijms24032867Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148Muhanad Ali0Miriam E. van Gent1Amy M. de Waal2Bjorn R. van Doodewaerd3Erik Bos4Roman I. Koning5Robert A. Cordfunke6Jan Wouter Drijfhout7Peter H. Nibbering8Department of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Immunology, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Immunology, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsSynthetic 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 <i>Staphylococcus aureus</i> and 20-fold regarding AMR <i>Acinetobacter baumannii</i> after 4 h. Interestingly, the antibiofilm activity of SAAP-148 NPs against AMR <i>S. aureus</i> and <i>A. baumannii</i> 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 <i>S. aureus</i> at 24 h. Overall, SAAP-148 NPs present a promising yet challenging approach for further development as treatment against bacterial infections.https://www.mdpi.com/1422-0067/24/3/2867antimicrobial peptideskin infectionPLGAnanoparticledrug delivery systembacterial |
| spellingShingle | Muhanad Ali Miriam E. van Gent Amy M. de Waal Bjorn R. van Doodewaerd Erik Bos Roman I. Koning Robert A. Cordfunke Jan Wouter Drijfhout Peter H. Nibbering Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148 International Journal of Molecular Sciences antimicrobial peptide skin infection PLGA nanoparticle drug delivery system bacterial |
| title | Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148 |
| title_full | Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148 |
| title_fullStr | Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148 |
| title_full_unstemmed | Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148 |
| title_short | Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148 |
| title_sort | physical and functional characterization of plga nanoparticles containing the antimicrobial peptide saap 148 |
| topic | antimicrobial peptide skin infection PLGA nanoparticle drug delivery system bacterial |
| url | https://www.mdpi.com/1422-0067/24/3/2867 |
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