Effect Of Drug Inorporation And Release On The Morphology Of Amphiphilic Copolymer Micelles

Amphiphilic copolymer micelles play an important role in the field of drug delivery and their drug release behavior is strongly influenced by size and morphology of micelles. Two types of amphiphilic block copolymers based on poly(e-caprolactone-b-L-lactide)/methoxy poly(ethylene glycol) (P(CL-b-LLA)-b-mPEG) and poly(e-caprolactone-b-D,L-lactide) /methoxy poly(ethylene glycol) (P(CL-b-DLLA-b- mPEG)) were used as the carriers, while indomethacin and vitamin E, which have different physical state and similar hydrophobicity, were chosen as model drugs. The morphological change of micelles during the process of drug incorporation and release was studied.Drug-loaded micelles were prepared by dialysis method. The morphologies of micelles were observed by transmission electron microscopy (TEM), atomic force microscopy (AFM) and laser light scattering (LLS). The results demonstrated that the morphology of the micelles which have crystalline cores changed from short rod-like cylinders to wormlike ones; whereas those have amorphous cores changed from spheres to cylinders. In addition, the evolvement behavior of the micelle morphologies upon the drug entrapment was dependent on the several parameters including the crystalline property of the core-forming blocks, the property of drugs and length of hydrophilic blocks. The mechanisms on morphological change of crystalline-coil micelles and coil-coil micelles were further discussed respectively.The thermal property were measured by differential scanning calorimetry (DSC) and it is observed that the drug molecules embedded in the crystalline cores will weaken and impair the crystallinity; drug loading efficiency of micelles were calculated by ultraviolet (UV) spectroscopy and the results showed that the entrapment of VE was higher than that of IMC and the micelles with amorphous cores solubilized more drugs rather than those with crystalline cores when the length of mPEG blocks were same.Evolvement in the micelle morphology was also observed during the period of drug release, which seemed to be the reverse process of drug incorporation. The substantial change appeared 2-5 h after the drug release.