title: Phytantriol Based "Stealth" Lyotropic Liquid Crystalline Nanoparticles for Improved Antitumor Efficacy and Reduced Toxicity of Docetaxel.
abstract: OBJECTIVE
  The present work focuses on design and development of surface functionalized LCNPs for improving tumor delivery of DTX.
  
  
  METHODS
  Phytantriol based "stealth" LCNPs were prepared using hydrotrope method and optimized. The potential of developed formulation was further assessed using cell culture experiments, in vivo pharmacokinetics, in vivo pharmacodynamics and toxicity studies.
  
  
  RESULTS
  A biphasic drug release pattern was observed with sustained release of drug till 72 h. In vitro cell culture experiments revealed efficient internalization within MCF-7 cells with 25.80-fold decrease in IC50 value for PEG-LCNPs as compared to free DTX. Mechanistic insights demonstrated preferential co-localization of LCNPs in the vicinity of the nucleus. Furthermore, in vivo pharmacokinetic studies revealed 14.45-fold enhancement in circulation half-life of PEG-LCNPs as compared to marketed formulation Taxotere®. In vivo efficacy studies PEG-LCNPs in DMBA induced breast cancer model revealed ~81% reduction in the tumor burden compared to Taxotere® which caused/achieve only 47% reduction or showed only 47% decrease. Furthermore, safety profile was noted for PEG-LCNPs as compared to Taxotere®, measured as a function of hepato- and nephro-toxicity.
  
  
  CONCLUSIONS
  Surface functionalization of LCNPsis a viable approach for improving the therapeutic potential of DTX.
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S., Nagar (Mohali), Punjab, 160062, India. sanyogjain@niper.ac.in.
authors.forename: Sanyog
authors.initials: S
authors.lastname: Jain
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S., Nagar (Mohali), Punjab, 160062, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Bhankur
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S., Nagar (Mohali), Punjab, 160062, India.
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Swarnakar
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S., Nagar (Mohali), Punjab, 160062, India.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Thanki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry; D005233:Fatty Alcohols / Q000737:chemistry*; D005260:Female; D006207:Half-Life; D006801:Humans; D050866:Liquid Crystals / Q000737:chemistry*; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D043823:Taxoids / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005233:Fatty Alcohols; D043823:Taxoids; D000077143:Docetaxel; D011092:Polyethylene Glycols; C508873:3,7,11,15-tetramethyl-1,2,3-hexadecanetriol
keywords: DMDA model; PEGylation; docetaxel; in vivo antitumor efficacy; liquid crystalline nanoparticles (LCNPs); surface functionalization