title: PLGA nanoparticles stabilized with cationic surfactant: safety studies and application in oral delivery of paclitaxel to treat chemical-induced breast cancer in rat.
abstract: OBJECTIVE
  This study was carried out to formulate poly(lactide-co-glycolide) (PLGA) nanoparticles using a quaternary ammonium salt didodecyl dimethylammonium bromide (DMAB) and checking their utility to deliver paclitaxel by oral route.
  
  
  METHODS
  Particles were prepared by emulsion solvent diffusion evaporation method. DMAB and particles stabilized with it were evaluated by MTT and LDH cytotoxicity assays. Paclitaxel was encapsulated in these nanoparticles and evaluated in a chemical carcinogenesis model in Sprague Dawley rats.
  
  
  RESULTS
  MTT and LDH assays showed the surfactant to be safe to in vitro cell cultures at concentrations <33 microM. PLGA nanoparticles prepared using this stabilizer were also found to be non-toxic to cell lines for the duration of the study. When administered orally to rats bearing chemically induced breast cancer, nanoparticles were equally effective/better than intravenous paclitaxel in cremophor EL at 50% lower dose.
  
  
  CONCLUSIONS
  This study proves the safety and utility of DMAB in stabilizing preformed polymers like PLGA resulting in nanoparticles. This preliminary data provides a proof of concept of enabling oral chemotherapy by efficacy enhancement for paclitaxel.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, The John Arbuthnott Building, University of Strathclyde, Glasgow, G4 0NR, UK.
authors.forename: V
authors.initials: V
authors.lastname: Bhardwaj
authors.forename: D D
authors.initials: DD
authors.lastname: Ankola
authors.forename: S C
authors.initials: SC
authors.lastname: Gupta
authors.forename: M
authors.initials: M
authors.lastname: Schneider
authors.forename: C-M
authors.initials: CM
authors.lastname: Lehr
authors.forename: M N V Ravi
authors.initials: MN
authors.lastname: Kumar
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000188:drug therapy*; D018938:Caco-2 Cells; D002412:Cations / Q000737:chemistry*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004337:Drug Carriers; D004355:Drug Stability; D005260:Female; D006801:Humans; D053769:Nanocapsules / Q000737:chemistry* / Q000592:standards; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D010316:Particle Size; D011098:Polyglactin 910 / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D002412:Cations; D004337:Drug Carriers; D053769:Nanocapsules; D013501:Surface-Active Agents; D011098:Polyglactin 910; D017239:Paclitaxel