Antimicrobial peptide-grafted PLGA-PEG nanoparticles to fight bacterial wound infections.

Wound infection treatment with antimicrobial peptides (AMPs) is still not a reality, due to the loss of activity . 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--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, 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 against , and 16-32 μg mL against . Moreover, AMP grafting accelerates killing kinetics, from 1-2 h to 15 min for and from 6-8 h to 0.5-1 h for . NP activity in a simulated wound fluid is maintained for and decreases slightly for . 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.