Dual Arginine and Glutamic Amino Acids Delivery Effectiveness of Injectable Chitosan-Poloxamer P407 towards Wound Healing Application

Abstract

for tissue regeneration [5]. Chitosan has good biocompatibility, low toxicity, and rapid biodegradability. Various studies proposed the great pharmaceutical application of chitosan, including anti-bacteria, antiinflammation, hemostasis, etc. [6,7]. Furthermore, chitosan contains abundant functional groups on its backbone; therefore, it is easy to modify or fabricate to optimize the hydrogel structure [6][7][8]. For example, chitosan could be co-polymerization with pluronic F127 to form the thermal sensitive hydrogel [6,8]. The system was considered an effective platform for drug delivery and tissue regeneration [5][6][7]. Poloxamer, an amphiphilic, thermo-sensitive, and FDA-approved Triblock copolymer of poly (ethylene oxide) and poly (propylene oxide), is one of the most studied platforms for the preparation of highly efficient hydrogels [5,6,8]. Chitosan-grafted poloxamer is widely exploited in cartilage regeneration, wound healing, burn healing, and anti-cancer drug delivery [7,[9][10][11][12][13].L-Arginine (Arg) is an essential amino acid that helps to prevent and treat circulatory diseases, alleviate fatigue, and stimulate the immune system. Arg is also known as endothelial nitric oxide synthase enzyme (eNOS) substrate [14], responsible for Nitric Oxide (NO) synthesis [15]. NO creates the signal for macrophage activation leading to the migration of fibroblast cells in wound healing process [14]. Along with Arg, L-Glutamic acid (Glu) is a necessary amino acid in the body, a precursor for collagen synthesis [15]. Collagen is a