Abstract:
:Polymeric prodrugs of mPEG-PLA-haloperidol (methoxypoly(ethylene glycol)-b-poly(lactic acid)) can self-assemble into nanoscale micelle-like structures in aqueous solutions. mPEG-PLA-haloperidol was prepared 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 prodrugs in water were characterized using a variety of techniques. The mPEG-PLA and prodrug micelles were found 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 electron microscopy (cryo-TEM) and were consistent with the DLS results. Cryo-TEM and proton NMR confirmed that the micelles were spherical in shape. DLS was also used to determine the aggregation numbers of the micelles. The aggregation numbers ranged from 351 to 603. The change in aggregation number was dependent on the total drug incorporation into the micelle core. Critical micelle concentrations were determined for the various micelle/drug formulations and found to range from 3 to 14 microg/mL. Finally, drug was incorporated into the micelle core using the conjugate, free drug with a saturated aqueous phase during production, or a combination of both techniques. Drug incorporation could be increased from 3% to 20% (w/w) using the different formulations.
journal_name
Biomacromoleculesjournal_title
Biomacromoleculesauthors
Hans M,Shimoni K,Danino D,Siegel SJ,Lowman Adoi
10.1021/bm050188kkeywords:
subject
Has Abstractpub_date
2005-09-01 00:00:00pages
2708-17issue
5eissn
1525-7797issn
1526-4602journal_volume
6pub_type
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