TY - JOUR
T1 - Antimicrobial peptide-grafted PLGA-PEG nanoparticles to fight bacterial wound infections
AU - Ramôa, António Miguel
AU - Campos, Filipa
AU - Moreira, Luís
AU - Teixeira, Cátia
AU - Leiro, Victoria
AU - Gomes, Paula
AU - Neves, José das
AU - Martins, M. Cristina L.
AU - Monteiro, Cláudia
N1 - Publisher Copyright:
© 2023 The Royal Society of Chemistry.
PY - 2022/11/23
Y1 - 2022/11/23
N2 - Wound infection treatment with antimicrobial peptides (AMPs) is still not a reality, due to the loss of activity in vivo. Unlike the conventional strategy of encapsulating AMPs on nanoparticles (NPs) leaving activity dependent on the release profile, this work explores AMP grafting to poly(d,l-lactide-co-glycolide)-polyethylene glycol NPs (PLGA-PEG NPs), whereby AMP exposition, infection targeting and immediate action are promoted. NPs are functionalized with MSI-78(4-20), an equipotent and more selective derivative of MSI-78, grafted through a thiol-maleimide (Mal) Michael addition. NPs with different ratios of PLGA-PEG/PLGA-PEG-Mal are produced and characterized, with 40%PLGA-PEG-Mal presenting the best colloidal properties and higher amounts of AMP grafted as shown by surface charge (+8.6 ± 1.8 mV) and AMP quantification (326 μg mL−1, corresponding to 16.3 μg of AMP per mg of polymer). NPs maintain the activity of the free AMP with a minimal inhibitory concentration (MIC) of 8-16 μg mL−1 against Pseudomonas aeruginosa, and 16-32 μg mL−1 against Staphylococcus aureus. Moreover, AMP grafting accelerates killing kinetics, from 1-2 h to 15 min for P. aeruginosa and from 6-8 h to 0.5-1 h for S. aureus. NP activity in a simulated wound fluid is maintained for S. aureus and decreases slightly for P. aeruginosa. Furthermore, NPs do not demonstrate signs of cytotoxicity at MIC concentrations. Overall, this promising formulation helps unleash the full potential of AMPs for the management of wound infections.
AB - Wound infection treatment with antimicrobial peptides (AMPs) is still not a reality, due to the loss of activity in vivo. Unlike the conventional strategy of encapsulating AMPs on nanoparticles (NPs) leaving activity dependent on the release profile, this work explores AMP grafting to poly(d,l-lactide-co-glycolide)-polyethylene glycol NPs (PLGA-PEG NPs), whereby AMP exposition, infection targeting and immediate action are promoted. NPs are functionalized with MSI-78(4-20), an equipotent and more selective derivative of MSI-78, grafted through a thiol-maleimide (Mal) Michael addition. NPs with different ratios of PLGA-PEG/PLGA-PEG-Mal are produced and characterized, with 40%PLGA-PEG-Mal presenting the best colloidal properties and higher amounts of AMP grafted as shown by surface charge (+8.6 ± 1.8 mV) and AMP quantification (326 μg mL−1, corresponding to 16.3 μg of AMP per mg of polymer). NPs maintain the activity of the free AMP with a minimal inhibitory concentration (MIC) of 8-16 μg mL−1 against Pseudomonas aeruginosa, and 16-32 μg mL−1 against Staphylococcus aureus. Moreover, AMP grafting accelerates killing kinetics, from 1-2 h to 15 min for P. aeruginosa and from 6-8 h to 0.5-1 h for S. aureus. NP activity in a simulated wound fluid is maintained for S. aureus and decreases slightly for P. aeruginosa. Furthermore, NPs do not demonstrate signs of cytotoxicity at MIC concentrations. Overall, this promising formulation helps unleash the full potential of AMPs for the management of wound infections.
UR - http://www.scopus.com/inward/record.url?scp=85144032387&partnerID=8YFLogxK
U2 - 10.1039/d2bm01127a
DO - 10.1039/d2bm01127a
M3 - Article
C2 - 36458466
AN - SCOPUS:85144032387
SN - 2047-4830
VL - 11
SP - 499
EP - 508
JO - Biomaterials Science
JF - Biomaterials Science
IS - 2
ER -