1 Department of Chemistry and Biochemistry, Concordia University, Montreal, QuebecH4B 1R6, Canada.
2 Centre for NanoScience Research, Concordia University, Montreal, QuebecH4B 1R6, Canada.
3 FRQNT Centre Québécois sur les Matériaux Fonctionnels-Quebec Centre for Advanced Materials, McGill University, 845 Sherbrooke Street West, Montréal, QuebecH3A 0G4, Canada.
4 Faculty of Pharmacy, Alexandria University, Alexandria5424041, Egypt.
5 Département de Chimie, Université de Montréal, Complexe des sciences, C.P. 6128, succursale Centre-ville, Montréal, QuebecH3C 3J7, Canada.

Antimicrobial peptides, such as GL13K, have a high binding selectivity toward bacterial membranes, while not affecting healthy mammalian cells at therapeutic concentrations. However, delivery of these peptides is challenging since they are susceptible to proteolytic hydrolysis and exhibit poor cellular uptake. A protective nanocarrier is thus proposed to overcome these obstacles. We investigate the potential to employ biodegradable phytoglycogen nanoparticles as carriers for GL13K using a simple loading protocol based on electrostatic association rather than chemical conjugation, eliminating the need for control of chemical cleavage for release of the peptide in situ. Both the native (quasi-neutral) and carboxymethylated (anionic) phytoglycogen were evaluated for their colloidal stability, loading capacity, and release characteristics. We show that the anionic nanophytoglycogen carries a greater cationic GL13K load and exhibits slower release kinetics than native nanophytoglycogen. Isotope exchange measurements demonstrate that the antimicrobial peptide is entrapped in the pores of the dendritic-like macromolecule, which should provide the necessary protection for delivery. Importantly, the nanoformulations are active against a Pseudomonas aeruginosa clinical isolate at concentrations comparable to those of the free peptide and representative, small molecule antibiotics. The colloidal nanocarrier preserves peptide stability and antimicrobial activity, even after long periods of storage (at least 8 months).