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.
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Authors | Arun K Iyer, Khaled Greish, Jun Fang, Ryoichi Murakami, Hiroshi Maeda |
Journal | Biomaterials
(Biomaterials)
Vol. 28
Issue 10
Pg. 1871-81
(Apr 2007)
ISSN: 0142-9612 [Print] Netherlands |
PMID | 17208294
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biocompatible Materials
- Maleates
- Metalloporphyrins
- Micelles
- Polystyrenes
- Protoporphyrins
- copoly(styrene-maleic acid)-zinc protoporphyrin
- zinc protoporphyrin
- Heme Oxygenase (Decyclizing)
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Topics |
- Biocompatible Materials
(chemistry)
- Diffusion
- Drug Delivery Systems
(methods)
- Drug Stability
- Heme Oxygenase (Decyclizing)
(antagonists & inhibitors)
- Maleates
(chemistry)
- Materials Testing
- Metalloporphyrins
(chemistry)
- Micelles
- Nanostructures
(chemistry, ultrastructure)
- Particle Size
- Polystyrenes
(chemistry)
- Protoporphyrins
(administration & dosage, chemistry)
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