Nanoliposomal oxaliplatin ameliorates chemotherapy-induced neuropathy

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is an important adverse effect of treatment with oxaliplatin (OXA). We have developed PEGylated nanoliposomal oxaliplatin (OXA-LIP) and tested its activity in an animal model of CIPN. OXA-LIPs were prepared using a combination of egg yolk lecithin, cholesterol, and DSPE-mPEG2000 (at ratios 400, 80, and 27 mg). These liposomes were characterized using several different methods (e.g., polydispersity index (PDI), and zeta potential, FESEM). The in vivo study was performed in 15 male rats comprising three groups: a negative control (normal saline) OXA, and OXA-LIP. These were injected intraperitoneally at a concentration of 4 mg/kg on two consecutive days every week, for 4 weeks. After that, CIPN was assessed using the hotplate and acetonedropmethods. Oxidative stress biomarkers such as SOD, catalase, MDA, and TTG were measured in the serum samples. The functional disturbances of the liver and kidney were assessed by measuring the serum levels of ALT, AST, creatinine, urea, and bilirubin. Furthermore, hematological parameters were determined in the three groups. The OXA-LIP had an average particle size, PDI, and zeta potential of 111.2 ± 1.35 nm, 0.15 ± 0.045, and -52.4 ± 17 mV, respectively. The encapsulation efficiency of OXA-LIP was 52% with low leakage rates at 25 °C.Thermal hyperalgesia changes showed OXA has significant effects in the induction of neuropathy on days 7, 14, and 21 compared to the control group. OXA had a significantly greater sensitivity than the OXA-LIP and control groups in the thermal allodynia test (P < 0.001). OXA-LIP administration did not show significant effects on the changes of oxidative stress, biochemical factors, and cell count. Our findings provide a proof of concept on the potential application of oxaliplatin encapsulated with PEGylated nanoliposome to ameliorate the severity of neuropathy, supporting further studies in clinical phases to explore the value of this agent for Chemotherapy-induced peripheral neuropathy.

Keywords: Neuropathy; Oxaliplatin; Oxidative stress; PEGylated nano-liposome.