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Vincristine Sulfate Loaded Dextran Microspheres Amalgamated With Thermosensitive Gel Offered Sustained Release and Enhanced Cytotoxicity in THP-1, Human Leukemia Cells: In Vitro and in Vivo Study

Vincristine Sulfate Loaded Dextran Microspheres Amalgamated With Thermosensitive Gel Offered Sustained Release and Enhanced Cytotoxicity in THP-1, Human Leukemia Cells: In Vitro and in Vivo Study

Vivek Thakur, Preeti Kush, Ravi Shankar Pandey, Upendra Kumar Jain, Ramesh Chandra, Jitender Madan

Mater Sci Eng C Mater Biol Appl. 2016 Apr 1;61:113-22.

PMID: 26838831

Abstract:

Vincristine sulfate (VCS) is a drug of choice for the treatment of childhood and adult acute lymphocytic leukemia, Hodgkin's, non-Hodgkin's lymphoma as well as solid tumors including sarcomas. However, poor biopharmaceutical and pharmacokinetic traits of VCS like short serum half-life (12 min), high dosing frequency (1.4 mg/m(2) per week for 4 weeks) and extensive protein binding (75%) limit the clinical potential of VCS in cancer therapy. In present investigation, injectable vincristine sulfate loaded dextran microspheres (VCS-Dextran-MSs) were prepared and amalgamated with chitosan-β-glycerophosphate gel (VCS-Dextran-MSs-Gel) to surmount the biopharmaceutical and pharmacokinetic limitations of VCS that consequently induced synergistic sustained release pattern of the drug. Particle size and zeta-potential of VCS-Dextran-MSs were measured to be 6.8 ± 2.4 μm and -18.3 ± 0.11 mV along with the encapsulation efficiency of about 60.4 ± 4.5%. Furthermore, VCS-Dextran-MSs and VCS-Dextran-MSs-Gel exhibited slow release pattern and 94.7% and 95.8% of the drug was released in 72 h and 720 h, respectively. Results from cell viability assay and pharmacokinetic as well as histopathological analysis in mice indicated that VCS-Dextran-MSs-Gel offers superior therapeutic potential and higher AUClast than VCS-Dextran-MSs and drug solution. In conclusion, VCS-Dextran-MSs-Gel warrants further preclinical tumor growth study to scale up the technology.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP2068782-B	Vincristine sulfate (assay)		2068-78-2	Price

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