Synthesis and Characterization of mPEG-PLA Prodrug Micelles
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- 作者：Meredith Hans ; Karin Shimoni ; Dganit Danino ; Steven J. Siegel ; and Anthony Lowman
- 刊名：Biomacromolecules
- 出版年：2005
- 出版时间：September 2005
- 年：2005
- 卷：6
- 期：5
- 页码：2708 - 2717
- 全文大小：594K
- 年卷期：v.6,no.5(September 2005)
- ISSN：1526-4602
文摘
Polymeric prodrugs of mPEG-PLA-haloperidol (methoxypoly(ethylene glycol)-b-poly(lactic acid)) canself-assemble into nanoscale micelle-like structures in aqueous solutions. mPEG-PLA-haloperidol wasprepared and characterized using 1H and 13C NMR. The conjugation efficiency was found to be 64.8 ±21%. Micelles that form spontaneously upon solubilization of the mPEG-PLA and the polymeric prodrugsin water were characterized using a variety of techniques. The mPEG-PLA and prodrug micelles werefound to have diameters of 28.73 ± 1.45 and 49.67 ± 4.29 nm, respectively, using dynamic light scattering(DLS). The micelle size and polydispersity were also evaluated with cryogenic transmission electronmicroscopy (cryo-TEM) and were consistent with the DLS results. Cryo-TEM and proton NMR confirmedthat the micelles were spherical in shape. DLS was also used to determine the aggregation numbers of themicelles. The aggregation numbers ranged from 351 to 603. The change in aggregation number was dependenton the total drug incorporation into the micelle core. Critical micelle concentrations were determined forthe various micelle/drug formulations and found to range from 3 to 14 
g/mL. Finally, drug was incorporatedinto the micelle core using the conjugate, free drug with a saturated aqueous phase during production, or acombination of both techniques. Drug incorporation could be increased from 3% to 20% (w/w) using thedifferent formulations.
g/mL. Finally, drug was incorporatedinto the micelle core using the conjugate, free drug with a saturated aqueous phase during production, or acombination of both techniques. Drug incorporation could be increased from 3% to 20% (w/w) using thedifferent formulations.