title: Nanovesicular carrier-based formulation for skin cancer targeting: evaluation of cytotoxicity, intracellular uptake, and preclinical anticancer activity.
abstract: BACKGROUND
  Skin cancer has turned into global epidemic leading to higher incidences among cancer stricken population.
  
  
  OBJECTIVE
  The aim of the present investigation is to evaluate the anticancer potential and intracellular uptake of a novel nanovesicular formulation of 5-FU.
  
  
  METHODS
  Detailed intracellular uptake study in conjunction with estimation of intracellular reactive oxygen species was done using skin melanoma cell lines (A375) along with cytotoxicity studies. To further obtain the mechanistic insights into inhibition of tumor cell proliferation, cell-cycle arrest studies were conducted. The preclinical anticancer activity was carried out employing in vivo DMBA-croton oil-induced skin cancer model in mice.
  
  
  CONCLUSIONS
  Significant reduction in the number of papillomas was observed in skin cancer-bearing mice on treatment with nanovesicular formulation (51.4 ± 3.2%) in comparison with marketed formulation (21.3 ± 2.1%) of 5-FU. Tumor volume was found to be reduced to 46.3 ± 3.5% with prepared formulation, whereas the marketed formulation-treated group showed the reduction of 18.6 ± 1.8% in comparison with the control (untreated) group.
  
  
  CONCLUSIONS
  The results of present study demonstrated that nanovesicular formulation of 5-FU possessed the enhanced anticancer activity which could be attributed to better intracellular uptake, cellular retention, and sustained release of drug.
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University , Amritsar, Punjab , India .
authors.forename: Subheet Kumar
authors.initials: SK
authors.lastname: Jain
authors.forename: Richa
authors.initials: R
authors.lastname: Puri
authors.forename: Mohit
authors.initials: M
authors.lastname: Mahajan
authors.forename: Subodh
authors.initials: S
authors.lastname: Yadav
authors.forename: C M
authors.initials: CM
authors.lastname: Pathak
authors.forename: N
authors.initials: N
authors.lastname: Ganesh
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000179:Acrylates; D004337:Drug Carriers; D017382:Reactive Oxygen Species; C453622:carbopol 934P; D005472:Fluorouracil
keywords: Cytotoxicity assay; nanovesicular formulation; pharmacodynamic study; skin cancer; skin cancer cell line; tumor concentration