Arginine-conjugated chitosan nanoparticles for topical arginine release in wounds

Abstract

Arginine is a conditionally essential amino acid in the healing process. Catabolized by nitric oxide synthases and arginases, arginine is rapidly depleted during the healing process of chronic wounds, hampering collagen synthesis, and other proteins that contribute to tissue regeneration. The administration of arginine at a wound site can compensate for its deficiency. To avoid its rapid metabolism, its sustained release in the wound bed is desired. In this work, arginine was encapsulated in arginine-modified chitosan nanoparticles (NP-CHITARG) to have arginine-conjugated chitosan polymer (CHITARG) as a late source of arginine after the sustained release of the drug encapsulated from the nanoparticle. The conjugate CHITARG was characterized by proton nuclear magnetic resonance, thermal and elemental analysis, and scanning electron microscopy. NP-CHITARG, obtained by a modified nanoprecipitation method, was characterized in terms of size, polydispersity, zeta potential, morphology, and encapsulation efficiency of arginine. In vitro cytotoxicity assay was also performed on fibroblast cells (NIH-3T3). NP-CHITARG dispersions showed 177 ± 35 nm, positive zeta potential, and pH 6. Encapsulation of arginine in NP-CHITARG increased 1.5-fold the size of the nanoparticles and decreased the pH of the dispersions to 5.5. NP-CHITARG was able to encapsulate about 10% of arginine. The release of arginine remained constant and slow after a burst release of approximately 20%. Nanoparticles were not cytotoxic to fibroblasts. The amount of arginine slowly released over time combined with CHITARG's antimicrobial and anticoagulant properties suggest a promising effect of nanoparticles in the treatment of wounds.