Pegylated nanoliposomal cisplatin ameliorates chemotherapy-induced peripheral neuropathy

• Published in: International journal of pharmaceutics 2024-03, Vol.652, p.123839-123839, Article 123839
• Main Authors: Moetamani-Ahmadi, Mehrdad, Mahmoud Ahmadzadeh, Amir, Alaei, Maryam, Zafari, Nima, Negahbanzaferanloo, Zhara, Pourbagher-Shahri, Ali Mohammad, Forouzanfar, Fatemeh, Fiuji, Hamid, Mahaki, Hanie, Khazaei, Majid, Gataa, Ibrahim Saeed, Ferns, Gordon A., Peters, Godefridus J., Batra, Jyotsna, Lam, King-Yin, Giovannetti, Elisa, TanzadehPanah, Hamid, Avan, Amir
• Format: Article
• Language: English
• Subjects: Cisplatin; Drug delivery; Glial cell; Oxidative stress; PEGylated liposome; Peripheral neuropathy
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.123839

[Display omitted] •Nanoliposomal cisplatin can limit Chemotherapy-induced peripheral neuropathy in an animal model.•Nanoliposomal cisplatin alleviates thermal hypersensitivity to heat assessed by hot-plate test.•Acetone drop test revealed reduced thermal sensitivity to cold using nanoliposomal cisplatin.•Application of PEGylated nanoliposomal cisplatin prevents satellite cell activation in DRG of rats.•Cisplatin-loaded PEGylated liposome nanoparticles can modulate oxidative stress in rats. Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse effect of cisplatin. The current study aimed to determine whether PEGylated nanoliposomal cisplatin can limit CIPN in an animal model. Cisplatin-loaded PEGylated liposome nanoparticles (Cis-PL) were produced as a combination of lecithin, cholesterol, and DSPE-mPEG2000 in a molar ratio of 50:45:5 and were characterized by polydispersity index (PDI), zeta potential, Field emission scanning electron microscopy (FESEM) analysis, as well as encapsulation efficiency (EE). Fifteen male rats were provided and randomly divided into 3 groups including Cis-PL group, cisplatin group, and control group. Behavioural tests (hot-plate test and acetone drop test) were used for evaluating CIPN. Moreover, oxidative stress markers and histopathological analysis were applied. Treatment-related toxicity was assessed by haematological analysis as well as liver and renal function tests. Cis-PL had an average particle size of 125.4, PDI of 0.127, and zeta potential of −40.9 mV. Moreover, the Cis-PL exhibited a high EE as well as low levels of leakage rate at 25 °C. In a hot-plate test, paw withdrawal latency was longer in Cis-PL group in comparison to rats treated with cisplatin. A lower number of withdrawal responses was detected during acetone drop test in Cis-PL group than in cisplatin-treated rats. Assessment of oxidative stress markers showed that Cis-PL could improve oxidative stress. Additionally, histopathological assessment demonstrated that the number of satellite cells was significantly reduced in the dorsal root ganglion (DRG) of Cis-PL-treated rats compared with those treated with cisplatin. The cisplatin group had elevated white blood cells counts, reduced platelet counts, and higher levels of bilirubin, ALT (alanine aminotransferase, and AST (aspartate aminotransferase), and creatinine compared with the control group, which was ameliorated in Cis-PL group. Data from the current study support the previous hypoth