title: Enhanced anti-tumor efficacy of paclitaxel with PEGylated lipidic nanocapsules in presence of curcumin and poloxamer: In vitro and in vivo studies.
abstract: Cancer chemotherapeutic drug containing PEGylated lipidic nanocapsules (D-LNCs) were formulated by the controlled addition of organic phase (combined solution of paclitaxel and curcumin in a mixture of oleic acid and MPEG2000-DSPE (90:2.5 molar ratio) in acetone) to the aqueous phase (consist of Poloxamer 407 as emulsifying agents and glycerol as a co-solvent) at a temperature of 55-60°C followed by evaporation of organic solvent. The obtained pre-colloidal dispersion of D-LNCs was processed through high pressure homogenization to get more uniformly and nano-sized particles. Effect of concentration of emulsifying agent and process variables of high pressure homogenization (pressure and number of cycles) on average particle size and entrapment efficiency was further investigated by constructing Box-Behnken experimental design to achieve the optimum manufacturing process. D-LNCs were characterized by dynamic light scattering, scanning and transmission electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. In vitro release studies showed a sustained release pattern of drug from the PEGylated D-LNCs, whereas in vivo pharmacokinetic studies after a single-dose intravenous (i.v.) administration of paclitaxel (15mg/kg) in Ehrlich ascites tumor (EAT)-bearing female Swiss albino mice showed a prolonged circulation time and slower elimination of paclitaxel from D-LNCs as compared with marketed formulation (Paclitec®). From the plasma concentration vs. time profile, i.v. bioavailability (AUC0-∞) of paclitaxel from D-LNCs was found to be increased approximately 2.91-fold (P<0.001) as compared to Paclitec®. In vitro cell viability assay against MCF-7 and MCF-7/ADR cell lines, in vivo biodistribution studies and tumor inhibition study in EAT-bearing mice, all together prove its significantly improved potency towards cancer therapy.
authors.affiliation: Nanoformulation Research Laboratory, Faculty of Pharmacy, Hamdard University, New Delhi, India. Electronic address: md.anwar2008@gmail.com.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Anwar
authors.affiliation: Nanoformulation Research Laboratory, Faculty of Pharmacy, Hamdard University, New Delhi, India; LE STUDIUM(®) Loire Valley Institute for Advanced Studies, Centre-Val de Loire region, France; Nucleic Acids Transfer by Non Viral Methods, Centre de Biophysique Moléculaire, CNRS UPR4301, Rue Charles Sadron, 45071 Orléans Cedex 2, France.
authors.forename: Sohail
authors.initials: S
authors.lastname: Akhter
authors.affiliation: Nanoformulation Research Laboratory, Faculty of Pharmacy, Hamdard University, New Delhi, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Mallick
authors.affiliation: Nanoformulation Research Laboratory, Faculty of Pharmacy, Hamdard University, New Delhi, India.
authors.forename: Sharmistha
authors.initials: S
authors.lastname: Mohapatra
authors.affiliation: Nanoformulation Research Laboratory, Faculty of Pharmacy, Hamdard University, New Delhi, India.
authors.forename: Sobiya
authors.initials: S
authors.lastname: Zafar
authors.affiliation: Department. of Biosciences, Jamia Millia Islamia, New Delhi, India.
authors.forename: M Moshahid A
authors.initials: MMA
authors.lastname: Rizvi
authors.affiliation: Nanoformulation Research Laboratory, Faculty of Pharmacy, Hamdard University, New Delhi, India.
authors.forename: Asgar
authors.initials: A
authors.lastname: Ali
authors.affiliation: Nanoformulation Research Laboratory, Faculty of Pharmacy, Hamdard University, New Delhi, India. Electronic address: farhanja_2000@yahoo.com.
authors.forename: Farhan J
authors.initials: FJ
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001682:Biological Availability; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D045703:Emulsifying Agents / Q000737:chemistry; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D061986:MCF-7 Cells; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D045703:Emulsifying Agents; D008055:Lipids; D053769:Nanocapsules; D020442:Poloxamer; D011092:Polyethylene Glycols; D003474:Curcumin; D017239:Paclitaxel
keywords: Curcumin; Hemolytic toxicity; Lipidic nanocapsules; Paclitaxel; Poloxamer; Tumor inhibition