Synthesis and Evaluation of Low Molecular Weight Chitosan-Acetylcysteine Conjugate for Renal Targeting Therapy
- Author:
Xiao-Jing CAO
1
Author Information
- Publication Type:Journal Article
- Keywords: Antioxidant; Conjugate; Low molecular weight chitosan; N-acetylcysteine; Renal targeting delivery system
- From: Chinese Pharmaceutical Journal 2017;52(8):649-654
- CountryChina
- Language:Chinese
- Abstract: OBJECTIVE: To synthesize low molecular weight chitosan-acetylcysteine (LMWC-NAC) conjugate and investigate its renal targeting profile and the rapeutic effects in model mice with acute kidney injury (AKI).METHODS: NAC was conjugated to LMWC by EDC/NHS reaction and the LMWC-NAC conjugate was identified by 1H-NMR. The cellular uptake of LMWC-NAC conjugate and megalin receptor involved in this process was investigated in vitro. In addition, the tissue distribution of ICG-labelled LMWC-NAC conjugate was investigated in nude mice. AKI were induced by LPS intraperitoneal injection (20 mg·kg-1).The parameters including Scr, BUN, inflammatory factors (TNF-α and IL-1β), and oxidative stress (MDA) were determined and renal histology was observed. RESULTS: LMWC-NAC conjugate was successfully synthesized by the amide interaction.The in vitrostudies demonstrated that the uptake of LMWC-NAC conjugate was mediated by the megalin receptor on HK-2 cells, and the tissue distribution experiment indicated that LMWC-NAC conjugate was mainly accumulated in the kidney.LMWC-NAC conjugate significantly suppressed Scr, BUN, inflammatory factors and oxidative stress (P<0.01) and improved kidney injury. CONCLUSION: LMWC-NAC conjugate showed good renal targeting profile and effect in recovering renal functions, which indicates the potential of LMWC-NAC conjugate as a safe and efficient drug delivery system for the treatment of AKI.
