Author/Authors :
Mehrabi, Mohammad Reza Department of Nanobiotechnology - Pasteur Institute of Iran, Tehran, Iran , Shokrgozar, Mohammad Ali National Cell Bank of Iran - Pasteur Institute of Iran, Tehran, Iran , Toliyat, Tayebeh Department of Pharmaceutics -Tehran University of Medical Sciences, Tehran, Iran , Shirzad, Masoomeh Department of Nanobiotechnology - Pasteur Institute of Iran, Tehran, Iran , Izadyari, Azadeh Department of Nanobiotechnology - Pasteur Institute of Iran, Tehran, Iran , Zoghi Mofrad, Laya Department of Nanobiotechnology - Pasteur Institute of Iran, Tehran, Iran , Chiani, Mohsen Department of Nanobiotechnology - Pasteur Institute of Iran, Tehran, Iran , Akbarzadeh, Azim Department of Nanobiotechnology - Pasteur Institute of Iran, Tehran, Iran
Abstract :
Clinical application of vincristine sulfate as a chemotherapeutic agent is limited because of its low aqueous solubility and severe side effects. This study aimed to improve the bioavailability and reduce side effects of vincristine sulfate through entrapping in
PEGylated niosomes.We evaluated the anticancer activity of PEGylated niosomal vincristine sulfate (PEG-nVCR) in a mouse model of lymphoma induced by BCL1 clone 5B1b cell line. PEG-nVCR was prepared by the thin-film hydration method. The prepared niosomes were characterized by size, zeta potential, and entrapment efficiency. The drug release pattern, neurotoxicity experiment, and in
vivo anticancer activity of PEG-nVCR were evaluated by the dialysis diffusion method, rotarod performance test, and flow cytometry,
respectively. The mean particle size, zeta potential, and entrapment efficiency of nisomes were obtained around 220 nm, -19 mV, and 81%, respectively. A sustained release behavior was indicated by PEG-nVCR so that the maximum release of VCR from niosomes reached to 69% after 36h of incubation. After the treatment of mice by different formulations, a significant reduction in lymphoma
cells in the spleen was obtained for the PEG-nVCR, as compared to the free vincristine sulfate. In the neurotoxicity experiment, a 2.5-fold lower motor incoordination effect was observed for the PEG-nVCR group with respect to the free VCR group. According to these findings, it can be concluded that the PEGylated niosomal formulation could be a suitable carrier for the delivery of VCR to the lymphoma cells or other related cancer cells.
Keywords :
Vincristine Sulfate , Drug Delivery , Niosomes , Cytotoxicity , Neurotoxicity