TY - JOUR
T1 - Pegylated nanoliposomal cisplatin ameliorates chemotherapy-induced peripheral neuropathy
AU - Moetamani-Ahmadi, Mehrdad
AU - Mahmoud Ahmadzadeh, Amir
AU - Alaei, Maryam
AU - Zafari, Nima
AU - Negahbanzaferanloo, Zhara
AU - Pourbagher-Shahri, Ali Mohammad
AU - Forouzanfar, Fatemeh
AU - Fiuji, Hamid
AU - Mahaki, Hanie
AU - Khazaei, Majid
AU - Gataa, Ibrahim Saeed
AU - Ferns, Gordon A.
AU - Peters, Godefridus J.
AU - Batra, Jyotsna
AU - King-yin Lam, Alfred
AU - Giovannetti, Elisa
AU - TanzadehPanah, Hamid
AU - Avan, Amir
N1 - Publisher Copyright: © 2024 Elsevier B.V.
PY - 2024/3/5
Y1 - 2024/3/5
N2 - Background: 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. Methods: 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. Results: 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. Conclusions: Data from the current study support the previous hypothesis that Cisplatin-loaded PEGylated liposome could be a promising solution for CIPN in the future by modulating oxidative stress and preventing glial cell activation in DRG, suggesting further clinical studies to investigate the efficacy of this agent and its potential application in clinical practice.
AB - Background: 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. Methods: 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. Results: 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. Conclusions: Data from the current study support the previous hypothesis that Cisplatin-loaded PEGylated liposome could be a promising solution for CIPN in the future by modulating oxidative stress and preventing glial cell activation in DRG, suggesting further clinical studies to investigate the efficacy of this agent and its potential application in clinical practice.
KW - Cisplatin
KW - Drug delivery
KW - Glial cell
KW - Oxidative stress
KW - PEGylated liposome
KW - Peripheral neuropathy
UR - http://www.scopus.com/inward/record.url?scp=85185576556&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2024.123839
DO - 10.1016/j.ijpharm.2024.123839
M3 - Article
C2 - 38266944
SN - 0378-5173
VL - 652
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 123839
ER -