Light Controlled Drug Release System Based On Self-assembled Supramolecular Design And Synthesis

Recently, controlled drug release systems have become the main development direction in the area of pharmaceutical study based on the developing new biomedical materials. The study is focusing on the design of new drug carriers and new controlled release ways. Among these, photocontrolled drug release systems have attracted great interest because of its highly accurate and "clean" external stimulation with non-physical contact at any desired times and sites. By now, the research in the photo-controlled drug delivery systems is still concentrated on the fundamentally scientific questions and there are many problems to be solved. In this thesis, two systems are designed and studied:(1) Design and synthesis of photo-responsive supramolecular hydrogel. With the development of protein drugs, new drugs'carrier with higher performance is needed. Hydrogel has good biocompatibility, the retention of the activity of proteins, extension of circulation time, and reduction of toxicity and side effects, so hydrogels are being regarded as ideal materials to store and delivery proteins drug. In addition, supramolecular hydrogel based on non-covalent interactions has mild preparation conditions, easy modulation for the gelation process and injectable properties. Based on this, we graftedβ-cyclodextrin onto dextran and connected the coumarin phototrigger group with adamantane to the PEG to form theβ-cyclodextrin (host molecules) and adamantane (guest molecules) self-assembled supramolecular hydrogel under the host-guest interactions. In this system, dextran and PEG has good biocompatibility and no non-specific adsorption characteristics, and coumarin acts as a light trigger with long wavelength absorption and can be excited by two-photon mode. The UV-vis spectra showed that the photodecompostion happened and the rheological measurements demonstrated that different molar ratio of the host-guest affected viscosity of the hydrogel. Unfortunately, the gel-sol change of the hydrogel didn't proceeded completely after irradiation, which limited the further application of the hydrogel as a carrier to release the drug.(2) Design and synthesis of photoinduced electrical change drug release system based on supramolecular self-assembly. For many drug molecules, it is very hard to conjugate them with the carriers due to their non-activity for the chemical reactions and bad solubility. And then, most of the drug carriers are cationic polymers, and there is a serious problem of non-specific adsorption in the body. Thus, in this paper, we designed and synthesized a new photo-controlled drug release system based on the host-guest action betweenβ-cyclodextrin and hydrophobic drug molecules by supramolecular self-assembly. At first, hexanediamine modifiedβ-cyclodextrin was coupled with phototrigger coumarin by an isocyanate bond. And then, the whole molecule was further grafted on the dextran polymers. Under the irradiation of UV light, the isocyanate bond would be cleaved and theβ-cyclodextrin encapsulated drug would release from the dextran polymer carrier. The generated amino group ofβ-cyclodextrin would be "exposed" and made the composite with drug presented "electropositive ", which would be favorable for cell endocytosis since the cell is "electronegative". Then theβ-cyclodextrin would be further enzymolyzed in the cell and finally released drug. It provides us a new method for the future research of photo-controlled drug release system.