Polyethylene sebacate–doxorubicin nanoparticles for hepatic targeting.pdf

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Polyethylene sebacate–doxorubicin nanoparticles for hepatic targeting.pdf

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Polyethylene sebacate–doxorubicin nanoparticles for hepatic targeting

International Journal of Pharmaceutics 401 (2010) 113–122 Contents lists available at ScienceDirect International Journal of Pharmaceutics journa l homepage: www.e lsev ier .com/ locate / i jpharm Pharmaceutical Nanotechnology Polyethylene sebacate–doxorubicin nanoparticles for hepatic targeting Swati A. Guhagarkara, Rajiv V. Gaikwadb, Abdul Samadb, Vinod C. Malshec, Padma V. Devarajana,? a Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai, Maharashtra 400 019, India b Veterinary Nuclear Medicine Center, Department of Medicine, Bombay Veterinary College, Parel, Mumbai, Maharashtra 400 012, India c Advanced Agro Tech., Thane, Maharashtra 400602, India a r t i c l e i n f o Article history: Received 1 July 2010 Received in revised form 9 September 2010 Accepted 14 September 2010 Available online 18 September 2010 Keywords: Nanoprecipitation Doxorubicin Polyethylene sebacate Pullulan Hepatic targeting a b s t r a c t Thepresent studydiscussespolyethylene sebacate (PES)–doxorubicin (DOX)nanoparticles (PES–DOXNP) using pullulan as asialoglycoprotein receptor (ASGPR) ligand for hepatic targeting. Pullulan, a hydrophilic polymer served as ligand and as stealth agent. PES–DOXNPwere prepared bymodified nanoprecipitation using PES and Gantrez AN 119 (Gantrez), as complexing agent in the organic phase, while DOX was dissolved in the aqueous phase. Pullulan was adsorbed on the formed nanoparticles (PES–DOX–PUL). Intimate associationof PES andGantrez, and ionic complexationofDOXwithGantrez (confirmedbyFTIR), coupled with rapidity of nanoprecipitation resulted in nanoparticles with high entrapment efficiency and high drug loading. Nanoparticles were successfully freeze dried. Drug release from PES NP followed zero order kinetics. PES–DOX NP and PES–DOX–PUL exhibited low hemolytic potential and good serum stability. Comparative biodistribution study in rats using 99mTc labeled formulations revealed higher blood concentration an