Study On Preparation Of Rapamycin-loaded Micelles And Release Behavior

As a broad-spectrum immunosuppressive drugs, Rapamycin has low renal toxicity and anti-rejection activity, can treat a variety of autoimmune diseases. However, the solubility of Rapamycin in water is 2.6μg/ml, the poor water solubility limited its application both in clinical and commercial. Therefore, It is very important to increase its water solubility and increase its bioavailability. Due to the special structure, biodegradable dendrimer has been widely used as drug carrier.In this paper, the dendrimer was used as a drug carrier to package insoluble Rapamycin, and then we studied its release behavior.Hollow polymer micelles were prepared by dialysis method. Scanning electron microscopy observation indicate its hollow vesicle structure. We get the best conditions for preparing micelles from changing the experimental conditions. Choosing different structure of dendritic copolymer, the size of micelles would be different.We prepared Rapamycin micelles by dialysis method. The average drug content and encapsulation efficiency were 40% and 91%. The results showed that:the drug-loaded micelles has the same hollow vesicle structure; the drug content and encapsulation efficiency of the drug-loaded micelles significantly increased; in vitro release results show its obvious sustained release. As the incresing ratio of hydrophobic PLLA segment, the release rate of drug slow down, according to the different need, we can synthesis different dendrimer polymer carrier to obtain the required release rate.Several models of drug release were used to fit the vitro release of Rapamycin from drug-loaded micelles. From the fitting we found the secondary Gompertz is the best models, which can predict the true release of Rapamycin from drug-loaded micelles in vitro release.In this paper, the Rapamycin-loaded micelles which used biodegradable dendrimer, compared to the similar drug sustained-release capsules(or micelles) whiich were reported, has nearly double drug content and lower sustained-release, we can change the structure of the dendrimer to control the drug release speed,has greater clinical application.