Study On Drug Carriers And Artificial Transmembrane Channels Based On Cyclodextrin Derivatives And Acyclic Cucurbit[n]uril

Cyclodextrin and its derivatives have been widely used in drug carriers because of their good molecular recognition ability and high biological safety.It has a hydrophobic cavity and has a good recognition ability for poorly soluble drug molecules.It can significantly improve the water solubility of poorly soluble drugs,increase drug availability,and reduce toxic and side effects of drugs.Acyclic cucurbit[n]uril is a new type of supramolecular body.The cavity is very flexible,has good molecular recognition ability,and is easy to modify to facilitate its derivatization.In this paper,threeβ-cyclodextrin derivatives,two linear three-cavity molecules,and one type of acid-sensitive acyclic cucurbit[n]uril were designed and synthesized.And their specific performance was studied.The main research contents are as follows:1.A series of derivatizations ofβ-cyclodextrin.Threeβ-cyclodextrin derivatives were obtained,which have better water solubility and molecular recognition ability than naturalβ-cyclodextrin.The inclusion reactions of threeβ-cyclodextrin derivatives with podophyllotoxin molecules were studied separately.~1H NMR proved that the inclusion complex was successfully.The phase solubility curve determines the binding constant between the host and guest molecules.XRD showed that after the formation of the inclusion complex,a new phase was formed as an amorphous powder.DSC showed that the formation of inclusion complexes improved the thermal stability of podophyllotoxin.The formation of inclusion complexes greatly improves the water solubility of podophyllotoxin.Finally,the MTT experiment confirmed that the inclusion compound maintained good activity on tumor cells while reducing toxicity to normal cells2.A new class of three cavity molecules were synthesized by acyclic cucurbit[n]uril andβ-cyclodextrin derivatives.NMR and mass spectrometry showed that the compound was successfully prepared.Then,it is further verified by fluorescence experiment that it can form an artificial transmembrane channel and realize the transmission of K~+.3.The targeted or responsive systems are appealing therapeutic platforms for the development of next-generation precision medications.So,we design and prepare acid-controlled release complexes of podophyllotoxin(POD)and etoposide(VP-16)with p H-labile acyclic cucurbit[n]urils,and their characteristics and inclusion complexation behaviors were investigated via fluorescence spectroscopy,nuclear magnetic resonance and X-ray power diffraction.Cells incubated with complexes have been analyzed by high-content analysis(HCA),and cytotoxicity tests have been completed by MTT assay.The results showed that complexes with different binding constants can release the drug substance in the physiological p H environment of cancer cells,maintain good anticancer activity,and have low cytotoxicity.This provides a strategy about targeted and responsive systems of POD and VP-16 for clinical application.