title: High-loading nanosized micelles of copoly(styrene-maleic acid)-zinc protoporphyrin for targeted delivery of a potent heme oxygenase inhibitor.
abstract: Amphiphilic styrene-maleic acid (SMA) copolymer efficiently formed micelles with a potent heme oxygenase inhibitor-zinc protoporphyrin (ZnPP). The micelles were constructed by subtle pH adjustments to form non-covalent interaction between the hydrophobic ZnPP and amphiphilic SMA. The micelles (SMA-ZnPP) thus formed were nanoparticles with narrow size distribution in water (mean diameter 176.5nm), having tunable loading (from 15% to 60% w/w of ZnPP) with remarkable aqueous solubility. SMA-ZnPP had an average molecular size of 144kDa as determined by size-exclusion chromatography (SEC), this size is a marked increase from the molecular weight of free ZnPP (626.03Da), suggesting the formation of micellar structure. The micelles showed a constant ZnPP release rate of about 0.5%/day in vitro at neutral pH. SMA-ZnPP micelles inhibited splenic microsomal HO-1 activity, in a competitive and dose-dependent manner, with an apparent inhibitory constant (K(i)) of 0.12mum, comparable to free ZnPP and also exhibited marked cytotoxic effect on KYSE-510 human esophageal cancer cells. The unique features of SMA-ZnPP micelles are that they are nanoparticles in aqueous solution having high water solubility and loading, yet macromolecular in nature, which can be beneficial in targeted release of a potent HO-1 inhibitor.
authors.affiliation: Laboratory of Microbiology & Oncology, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Iyer
authors.forename: Khaled
authors.initials: K
authors.lastname: Greish
authors.forename: Jun
authors.initials: J
authors.lastname: Fang
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Murakami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maeda
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D004058:Diffusion; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D008298:Maleates / Q000737:chemistry*; D008422:Materials Testing; D008665:Metalloporphyrins / Q000737:chemistry*; D008823:Micelles; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure*; D010316:Particle Size; D011137:Polystyrenes / Q000737:chemistry*; D011524:Protoporphyrins / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D008298:Maleates; D008665:Metalloporphyrins; D008823:Micelles; D011137:Polystyrenes; D011524:Protoporphyrins; C518727:copoly(styrene-maleic acid)-zinc protoporphyrin; C017803:zinc protoporphyrin; D006419:Heme Oxygenase (Decyclizing)