title: In vitro mechanistic study of cell death and in vivo performance evaluation of RGD grafted PEGylated docetaxel liposomes in breast cancer.
abstract: Objectives of the investigations were to prepare RGD grafted docetaxel liposomes (RGD-PEG-LP-DC) using supercritical fluid technology and evaluate it in vitro for cytotoxicity, DNA content analysis, mechanism of cell death, and in vivo for pharmacokinetic and biodistribution studies in BALB/c mice. The RGD-PEG-LP-DCs were found to be most cytotoxic in BT-20 and MDA-MB-231 cell lines. The flowcytometry results shows at 48 hours, 96% G2 phase arrest for RGD-PEG-LP-DC at 5 nM drug concentration. The mode of cell death was found to be mainly by necrosis at low drug equivalent concentration (1 nM) and by apoptosis at high drug equivalent concentration (10 nM). With increase in time and concentration the mode of cell death by apoptosis was found to be increasing. Biodistribution demonstrated that site specific drug distribution, t(1/2), and MRT improved significantly for RGD-PEG-LP-DC. From the studies site specific and sustained intracellular drug delivery from RGD-PEG-LP-DCs may provide promising strategy in enhancing embattled against breast cancer treatment. FROM
authors: Pharmacy Department, NDDS Laboratory, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Gujarat, India.
authors: Sachin
authors: S
authors: Naik
authors: Deepa
authors: D
authors: Patel
authors: Krishna
authors: K
authors: Chuttani
authors: Anil K
authors: AK
authors: Mishra
authors: Ambikanandan
authors: A
authors: Misra
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D000077143:Docetaxel; D005260:Female; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011817:Rabbits; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D053769:Nanocapsules; D009842:Oligopeptides; D043823:Taxoids; D000077143:Docetaxel; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid