Add time:08/20/2019         Source:sciencedirect.com

The present study discusses polyethylene sebacate (PES)–doxorubicin (DOX) nanoparticles (PES–DOX NP) using pullulan as asialoglycoprotein receptor (ASGPR) ligand for hepatic targeting. Pullulan, a hydrophilic polymer served as ligand and as stealth agent. PES–DOX NP were prepared by modified 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 association of PES and Gantrez, and ionic complexation of DOX with Gantrez (confirmed by FTIR), 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 and lower liver concentration of PES–DOX–PUL, confirming the long circulating nature of PES–DOX–PUL, and thereby the possibility of improved targeting to hepatocytes. Nanoparticles revealed lower DOX concentration in the heart suggestive of low cardiotoxicity. Our study presents a radically different yet simple approach for the design of PES–DOX nanoparticles with high drug loading for improved therapy in hepatic cancer.

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