title: 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.
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.
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Thakur
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab, India.
authors.forename: Preeti
authors.initials: P
authors.lastname: Kush
authors.affiliation: SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur, India.
authors.forename: Ravi Shankar
authors.initials: RS
authors.lastname: Pandey
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab, India.
authors.forename: Upendra Kumar
authors.initials: UK
authors.lastname: Jain
authors.affiliation: Department of Chemistry, University of Delhi, Delhi, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Chandra
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab, India. Electronic address: jitenderpharmacy@gmail.com.
authors.forename: Jitender
authors.initials: J
authors.lastname: Madan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008863:Microspheres; D014750:Vincristine / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D003692:Delayed-Action Preparations; D003911:Dextrans; D014750:Vincristine
keywords: Cytotoxicity; Dextran microspheres; Optimization; Pharmacokinetics; Thermosensitive gel; Vincristine sulfate