title: Synthesis and optimization of a novel polymeric micelle based on hyaluronic acid and phospholipids for delivery of paclitaxel, in vitro and in-vivo evaluation.
abstract: Novel polymeric micelles were synthesized based on hyaluronic acid (HA) and phospholipids (PEs) including 1,2-dimiristoyl phosphatidylethanolamine (DMPE) and 1,2-distearoyl phosphatidylethanolamine (DSPE). The newly developed micelles evaluated for the physicochemical properties including structural analysis by means of FTIR. Micelles were optimized for delivery of paclitaxel (PTX). The D-optimal design was applied in order to reach micelles with high entrapment efficiency (EE %) and minimum size, simultaneously. In this design the independent variables were the co-polymer type, the drug to polymer ratio and the formulation temperature, whereas the dependent variables were EE% and micelle size. The EE% of the optimized micelles was 46.8% and 59.9% for HA-DMPE and HA-DSPE micelles, respectively. The size of the optimized micelles was in the range of around 250 nm. In vitro release study of the optimized micelles showed that PTX was released from HA-DMPE and HA-DSPE micelles as long as 23 h and 34 h, respectively. Differential scanning calorimetry (DSC) studies showed a conversion of the crystalline PTX molecules into the amorphous form in the micelles. In vivo real time image analysis showed that micellar system was mostly accumulated in the liver, spleen and heart. Accelerated stability studies represented that PTX loaded micelle formulations were stable both physically and chemically at least in 6 months' time.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14399-56131, Iran.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Saadat
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14155-6451, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.affiliation: Department of Drug and Food Control, Faculty of Pharmacy and Pharmaceutical Quality Assurance Research Center, Tehran University of Medical Sciences, Tehran 14155-6451, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Khoshayand
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14399-56131, Iran.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14399-56131, Iran; Medical Biomaterials Research Center, Tehran University of Medical Sciences. Tehran 14399-56131, Iran. Electronic address: Dorkoosh@tums.ac.ir.
authors.forename: Farid A
authors.initials: FA
authors.lastname: Dorkoosh
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D055598:Chemical Phenomena; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D005456:Fluorescent Dyes / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry*; D008823:Micelles; D008956:Models, Chemical; D061848:Optical Imaging; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D051381:Rats; D012995:Solubility; D014018:Tissue Distribution; D051598:Whole Body Imaging
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008823:Micelles; D010714:Phosphatidylethanolamines; C038089:1,2-distearoylphosphatidylethanolamine; D006820:Hyaluronic Acid; D017239:Paclitaxel; C018525:1,2-dimyristoylphosphatidylethanolamine
keywords: Biodistribution; D-optimal design; Drug delivery; Hyaluronic acid; Paclitaxel; Polymeric micelle; Real time imaging