Trinitroglycerin-loaded chitosan nanogels for the treatment of Bilateral Renal Ischemic Reperfusion induced Acute Kidney Injury

Aim and Background: Acute kidney injury (AKI) is an inevitable complication in practice and leads to high kidney transplantation and patient mortality rates. Nitric oxide (NO) deficiency is an important factor in renal ischemia/reperfusion (I/R) injury conditions. Herein, trinitroglycerin-loaded chitosan nanogel (TNG-CSN) was developed for NO therapy to ameliorate AKI. CSN with good biocompatibility, biodegradability, and antioxidative properties could help to enhance TNG therapeutic effects. TNG is an efficient nitrovasodilator that causes rapid tissue oxygenation and could help restore hypoxic tissue, moreover, enhance endothelial cell regeneration. TNG-CSN sustain release platforms may offer a potential alternative for AKI conditions. Methods: TNG-CSN was prepared using chitosan cross-linked ionically with sodium tripolyphosphate (TPP) through the ionic-gelatin method. It was then characterized via fourier transform infrared (FT-IR), dynamic light scattering (DLS), zeta-potential, and electron microscopy, and also, drug loading and release profile were assessed. The anti-AKI and renoprotective effects of TNG-CSN were evaluated in vitro (cell viability, and various factors such as lactate dehydrogenase, lipid peroxide, and reactive oxygen species) and in vivo (serum biomarkers, and histopathological) examinations. Results and discussion: According to the results, characterization methods confirmed success in TNG-CSN preparation. TNG liberation gradually from CSN over 48 hours with initial burst release. The in vitro studies exhibited excellent biocompatibility of the TNG-CSN drug delivery system. TNG-CSN showed renoprotective effects (P 0.05) and alleviated I/R-induced histopathological injuries (P 0.05) compared to free TNG. Conclusion: Our results recommended that TNG-CSN enhances treatment efficacy for Renal (I/R) injury.