Supramolecular Polymers Based On Cyclodextrins For Drug And Gene Carriers

Supramolecular chemistry is a new interdisciplinary subject, which covers the fields of chemistry, materials, pharmacy, biology and so on. Supramolecular functional self-assemble is a hot topic in the field of supramolecular chemistry. The use of non covalent bond self-assembly can construct an ordered supramolecular with novel structure and function, which is of great significance for the exploration and design of novel functional drug delivery materials. The supramolecular self-assembly chemistry based on non covalent bonds can be said to have successfully broke the last hundred years "monopolize" of reaction chemistry based on the covalent bonds, especially in the field of materials chemistry. Cyclodextrin is an important research object in the field of supramolecular self-assembly chemistry, because cyclodextrins self-assembly for constructing nano size and morphology of different supramolecular drug carrier can provide a kind of preparation method at the molecular level. The drug carriers with different functions can be integrated into one body by the cyclodextrin based on self-assembly. Compared with covalent synthesis of drug delivery carriers, the noncovalent self-assembly method based on cyclodextrin has many advantages, such as the lack of need for special reaction equipment, mild reaction conditions, simplicity of operation, environmental friendliness, and easy batch preparation. The aim of this paper is to design a safe and efficient cyclodextrin supramolecular drug carriers and gene vector.Construction of cyclodextrin supramolecular drug carrier using the following strategy: â‘ A plurality of cyclodextrin is bonded to the side chains of the poly lysine. â‘¡The hydrophobic drug (scutellarin) is self-assembled into the cyclodextrin, so as to realize the drug carrier has high loading effect. The main contents and conclusions of the research on the construction of supramolecular drug carrier of cyclodextrin are summarized as follows:Firstly, the lateral branch of poly lysine-cyclodextrin (PL-Gly-CD) drug carrier was prepared by covalent synthesis method, the results of the peak area of nuclear magnetic resonance (NMR) showed that the drug carrier contained 10 cyclodextrin molecules. Secondly, host-guest recognition was induced by rapid mixing method in aqueous solution system. Drug carriers with high drug-loading rate was finally obtained through the drug and cyclodextrin self assembly. Again, the inclusion complexation behavior of the inclusion complex of hydrophobic drug (scutellarin) with PL-Gly-CD was proved by NMR, fluorescence analysis, thermal analysis and X-powder diffraction method. Saturated aqueous solution method showed that the carrier has a significant effect on the solubility of the drug. Finally, antitumor activity of the inclusion complex was tested by the cellular activity test, the results showed that the preparation of the drug assembly significantly improves the anticancer activity of the drug.Construction of cyclodextrin supramolecular gene vector using the following strategy: â‘ Functional molecules are synthesized. â‘¡The use of cyclodextrin bridged non covalent interactions, each functional molecules are integrated into one body, so as to construct multiple functional gene carrier.The main contents and conclusions of the research on the construction of supramolecular gene vector of cyclodextrin are summarized as follows:Firstly, folic acid-adamantane (FA-AD) molecules with tumor cell targeting function, polyethylene glycol-adamantane (PEG-AD) molecules with biocompatibility, and a high efficiency transfection function of the polyethylene-adamantane (PEI-CD) molecule were synthesized according to covalent bond method. Secondly, the recognization of cyclodextrin and adamantane was achieved by rapid mixing method in aqueous solution, and then, the multifunctional supramolecular nano gene vector of FA-AD, PEG-AD and PEI-CD three molecules self-assembly was obtained. The NMR was used to track the formation and self-assembly process, the results demonstrated the complexation of cyclodextrin and adamantane can form supramolecular nano gene vector. Again, gel electrophoresis, Zeta potential and atomic force were used to directly detect the coagulation ability and particle size of the self-assembly objects. The results indicated that the non viral genome assembly has a good effect coagulation ability, and the particle size of the non viral genome assembly is about 200nm. Finally, the safety and transfection efficiency of the the genome vector was evaluation by in-vitro cell research. The results showed that the preparation of non virus gene carrier not only has no significant cytotoxicity, but also can be recognized by target cells.