Synthesis And Evaluation Of HA-QDs-MEL

This dissertation successfully prepared a melphalan prodrug ofHA-QDs-MEL,which has an intelligent body tracing and receptor-mediatedtargeting. The delivery system transport melphalan of cytotoxic to specific tumorcells selectively (ovarian cancer, breast cancer, etc.), which release the drug toachieve a higher concentration in the site of tumor cells. We improve thebioavailability of the drug and increase the selection of anti-tumor. Therefore theadministration system not only can solve some issues such as toxic side effects andserious adverse reactions of chemotherapy drugs, but can do a tracer study ofpharmacological drugs.First,we through Hydrothermal prepared L-cysteine modified CdTe/CdSquantum dots which is water-soluble quantum dots with good biocompatibility.We prepared a cross-linking reaction product with the quantum dot ofL-Cys-CdTe/CdS and hyaluronic acid as the carrier of melphalan. Using a carboxylgroup on hyaluronic acid and an amino group on the quantum dots have a amidecondensation reaction. The experimental products of each step were Fouriertransform infrared spectroscopy and1H NMR characterization, proved successfulsynthesis.Finally, we prepared HA-QDs-MEL via amide condensation with carrier ofHA-QDs. Using the synthetic carrier HA-QDs and melphalan benzyl acetate whichhydrolysis under acidic conditions to obtain the final synthesis productHA-QDs-MEL. The principle of the reaction is to use part of the space on theHA-QDs free carboxyl group which activatied with EDC, then in the catalysator ofNHS, melphalan and free amino benzyl ester have a condensation reaction to formHA-QDs-MEL ester connected by an amide bond which hydrolyzed toHA-QDs-MEL under acidic conditions. HA-QDs-MEL was characterized by IRNMR.The results proved melphalan was junction to HA-QDs-MEL successfully.Particle size analysis revealed that diameter uniformly dispersed in about200to500nm.In this dissertation we have a drug release experiment to the delivery system ofHA-QDs-MEL. Releases of HA-QDs-MEL having certain pH selective and the release result is better in the acidic conditions of tumor cells, and also has a slowrelease effect which release curve is more gentle and a controlled-release effect.Itreveals the system which has controlled release and pH sensitivity.This dissertation also carried a cell drug evaluation system, the main job of thetoxicity tests, ingestion test, positioning test and receptor competitive inhibitionexperiments. Experimental results show that the toxicity of HA-QDs-MEL HAsgreatly improved, and reduced its lethal to normal cells. The drugs was swallowed bylysosomals, passed from the lysosomes to the nucleus, thereby killing the tumor cells.HA receptors inhibited by the competition experiments showed. HA receptors caninhibited HA-QDs-MEL which indicating CD44receptor targeting drug deliverysystem.