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...
Ausführliche Beschreibung
Autor*in: |
Muhanad Ali [verfasserIn] Miriam E. van Gent [verfasserIn] Amy M. de Waal [verfasserIn] Bjorn R. van Doodewaerd [verfasserIn] Erik Bos [verfasserIn] Roman I. Koning [verfasserIn] Robert A. Cordfunke [verfasserIn] Jan Wouter Drijfhout [verfasserIn] Peter H. Nibbering [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2023 |
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Übergeordnetes Werk: |
In: International Journal of Molecular Sciences - MDPI AG, 2003, 24(2023), 3, p 2867 |
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Übergeordnetes Werk: |
volume:24 ; year:2023 ; number:3, p 2867 |
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Link aufrufen |
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DOI / URN: |
10.3390/ijms24032867 |
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DOAJ080632378 |
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520 | |a 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. | ||
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10.3390/ijms24032867 doi (DE-627)DOAJ080632378 (DE-599)DOAJ766b77927e0e4ada8907f81ee317660a DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Muhanad Ali verfasserin aut Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. antimicrobial peptide skin infection PLGA nanoparticle drug delivery system bacterial Biology (General) Chemistry Miriam E. van Gent verfasserin aut Amy M. de Waal verfasserin aut Bjorn R. van Doodewaerd verfasserin aut Erik Bos verfasserin aut Roman I. Koning verfasserin aut Robert A. Cordfunke verfasserin aut Jan Wouter Drijfhout verfasserin aut Peter H. Nibbering verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 24(2023), 3, p 2867 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:24 year:2023 number:3, p 2867 https://doi.org/10.3390/ijms24032867 kostenfrei https://doaj.org/article/766b77927e0e4ada8907f81ee317660a kostenfrei https://www.mdpi.com/1422-0067/24/3/2867 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 3, p 2867 |
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10.3390/ijms24032867 doi (DE-627)DOAJ080632378 (DE-599)DOAJ766b77927e0e4ada8907f81ee317660a DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Muhanad Ali verfasserin aut Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. antimicrobial peptide skin infection PLGA nanoparticle drug delivery system bacterial Biology (General) Chemistry Miriam E. van Gent verfasserin aut Amy M. de Waal verfasserin aut Bjorn R. van Doodewaerd verfasserin aut Erik Bos verfasserin aut Roman I. Koning verfasserin aut Robert A. Cordfunke verfasserin aut Jan Wouter Drijfhout verfasserin aut Peter H. Nibbering verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 24(2023), 3, p 2867 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:24 year:2023 number:3, p 2867 https://doi.org/10.3390/ijms24032867 kostenfrei https://doaj.org/article/766b77927e0e4ada8907f81ee317660a kostenfrei https://www.mdpi.com/1422-0067/24/3/2867 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 3, p 2867 |
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10.3390/ijms24032867 doi (DE-627)DOAJ080632378 (DE-599)DOAJ766b77927e0e4ada8907f81ee317660a DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Muhanad Ali verfasserin aut Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. antimicrobial peptide skin infection PLGA nanoparticle drug delivery system bacterial Biology (General) Chemistry Miriam E. van Gent verfasserin aut Amy M. de Waal verfasserin aut Bjorn R. van Doodewaerd verfasserin aut Erik Bos verfasserin aut Roman I. Koning verfasserin aut Robert A. Cordfunke verfasserin aut Jan Wouter Drijfhout verfasserin aut Peter H. Nibbering verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 24(2023), 3, p 2867 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:24 year:2023 number:3, p 2867 https://doi.org/10.3390/ijms24032867 kostenfrei https://doaj.org/article/766b77927e0e4ada8907f81ee317660a kostenfrei https://www.mdpi.com/1422-0067/24/3/2867 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 3, p 2867 |
allfieldsGer |
10.3390/ijms24032867 doi (DE-627)DOAJ080632378 (DE-599)DOAJ766b77927e0e4ada8907f81ee317660a DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Muhanad Ali verfasserin aut Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. antimicrobial peptide skin infection PLGA nanoparticle drug delivery system bacterial Biology (General) Chemistry Miriam E. van Gent verfasserin aut Amy M. de Waal verfasserin aut Bjorn R. van Doodewaerd verfasserin aut Erik Bos verfasserin aut Roman I. Koning verfasserin aut Robert A. Cordfunke verfasserin aut Jan Wouter Drijfhout verfasserin aut Peter H. Nibbering verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 24(2023), 3, p 2867 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:24 year:2023 number:3, p 2867 https://doi.org/10.3390/ijms24032867 kostenfrei https://doaj.org/article/766b77927e0e4ada8907f81ee317660a kostenfrei https://www.mdpi.com/1422-0067/24/3/2867 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 3, p 2867 |
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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 |
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physical and functional characterization of plga nanoparticles containing the antimicrobial peptide saap-148 |
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Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148 |
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 <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. |
abstractGer |
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. |
abstract_unstemmed |
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. |
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3, p 2867 |
title_short |
Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148 |
url |
https://doi.org/10.3390/ijms24032867 https://doaj.org/article/766b77927e0e4ada8907f81ee317660a https://www.mdpi.com/1422-0067/24/3/2867 https://doaj.org/toc/1661-6596 https://doaj.org/toc/1422-0067 |
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