Synthesis And Evaluation Of PEGylation-hyaluronic Acid-melphalan

Melphalan (MEL) is widely used in the treatment of tumors,which is used in ovarian cancer and breast cancer, but also there are some defects, such as: poor selectivity, poor resistance and short half-life.A targeted drug delivery system was constructed in this dissertation, which was to improve the defects mentioned above and inhance its therapeutic effect against ovarian cancer. And studies the role of drug-related and performance evaluation. The main contents of this study are summarized as follows.1. It has been determined that the synthetic route, its optimal conditions and the best synthesis solution:Modificated hyaluronic acid with activated polyethylene glycol (PEG).Then cross-linked hyaluronic acid as carrier. Connected melphalan with PEG-HA-MEL, which is to improve the drug efficac in tumor cells. And1HNMR and IR was used to indieate the structure of product.2. Structures of the product's molecular weights were determined by gel permeation chromatography (GPC). And the released paclitaxel was meastred by HPLC, and studied the affection of pH, rotation speed and sample volume on the release rate. Both methods have good precision and accuracy. The results show that, due to the enzyme was very sensitive to pH, the release was high in the slightly acidic, and which was loss activity in the alkaline environment.And the impact of the speed and sample volume on the release is not great.3.'HNMR and electron microseopy (SEM) indieate the micelles had a core-shell structure,in which paclitaxel was enveloped in the core. The sizes of the self-assembly micelles of the amphiphilic bloek copolylners and the effects were studied by dynamic light seattering (DLS). Then the factors affecting it were studied.The results show that: the dosage will affect the particle size of the micelles; before or after frozen, there were a little change in micellar size.4. Cell culture experiments and MTT method was applied to study the inhibition of melphalan and PEG-HA-MEL micelles on tumor cells. The results suggested that the inhibition of PEG-HA-MEL was stronger effect than melphalan on tumor cells and the rate was relatively constant. 5.The studies on the stabilities of micells implied that it was good stabilities.When storage at sealed condition,the productiong has no significant change.And the drug release behavior and diameter of micells.but it sensitive to humidity, Freeze-dried powder become into pale yellow viscous gel.so it suggest micells should be storaged at sealed condition.