Nitric oxide releasing novel amino acid-derived polymeric nanotherapeutic with anti-inflammatory properties for rapid wound tissue regeneration

Abstract

Endogenous gasotransmitter nitric oxide (NO) is a central signalling molecule that modulates wound healing by maintaining homeostasis, collagen formation, wound contraction, anti-microbial action and accelerating tissue regeneration. The optimum delivery of NO using nanoparticles (NPs) is clinically challenging; hence, it is drawing significant attention in wound healing. Herein, a novel polymeric nanoplatform loaded with sodium nitroprusside (SP) NPs was prepared and used for wound healing to obtain the sustained release of NO in therapeutic quantities. SP NPs-induced excellent proliferation (∼300%) of mouse fibroblast (L929) cells was observed. With an increase in the SP NPs dose at 200 μg mL⁻¹ concentration, a 200% upsurge in proliferation was observed along with enhanced migration, and only 17.09 h were required to fill the 50% gap compared to 37.85 h required by the control group. Further, SP NPs showed an insignificant impact on the coagulation cascade, revealing safe wound-healing treatment when tested in isolated rat RBCs. Additionally, SP NPs exhibited excellent angiogenic activity at a 10 μg mL⁻¹ dose. Moreover, the formulated SP nanoformulation is non-irritant, non-toxic, and does not produce any skin sensitivity reaction on the rat's skin. Further, an in vivo wound healing study revealed that within 11 days of treatment with SP nanoformulation, 99.2 ± 1.0% of the wound was closed, while in the control group, only 45.5 ± 3.8% was repaired. These results indicate that owing to sustained NO release, the SP NP and SP nanoformulations are paramount with enormous clinical potential for the regeneration of wound tissues.