Skip to main content

Enhancement of Hydrophilic Drug Loading and Release Characteristics through Micellization with New Carboxymethyldextran-PEG Block Copolymers of Tunable Charge Density

مؤلف البحث
Ghareb Mohamed Soliman, Françoise M. Winnik
قسم البحث
مجلة البحث
International Journal of Pharmaceutics, doi:10.1016/j.ijpharm.2007.12.029
تصنيف البحث
1
عدد البحث
Vol. 356
سنة البحث
2008
المشارك في البحث
ملخص البحث

The micellization of a model cationic drug, diminazene diaceturate (DIM) and a series of new diblock copolymers, carboxymethyldextranpoly(ethylene glycols) (CMD-PEG), were evaluated as a function of the ionic charge density or degree of substitution (DS) of the carboxymethyldextran block and the molar ratio, [+]/[−], of positive charges provided by the drug to negative charges provided by CMD-PEG. Micelles ([+]/[−] = 2) incorporated up to 64% (w/w) DIM and ranged in hydrodynamic radius (RH) from 36 to 50 nm, depending on the molecular weight and DS of CMD-PEG. The critical association concentration (CAC) was on the order of 15-50 mg/L for CMD-PEG of DS > 60%, and ca. 100 mg/L for CMD-PEG of DS~30%. The micelles were stable upon storage in solution for up to 2 months and after freeze-drying in the presence of trehalose. They remained intact within the 4 < pH< 11 range and for solutions of pH 5.3, they resisted increases in salinity up to ~0.4 M NaCl in the case of CMD-PEG of high DS. However, micelles of DIM and a CMD-PEG of low DS (30%) disintegrated in solutions containing more than 0.1 M NaCl, setting a minimum value to the DS of copolymers useful in in-vivo applications. Sustained in-vitro DIM release was observed for micelles of CMD-PEG of high DS ([+]/[−] = 2).