Study On The Inclusion And Slow-release Performance Of Cucurbit[n]uril With Several Antitumor Drugs

In recent years,it has received great attention.Compared to other drug delivery systems(such as dendrimers,liposomes,micelles,carbon nanotubes and hydrogels,and polymers),macrocyclic compounds are often different due to their thermal and chemical stability and their ability to show advantages.The availability of nanostructures and their various sizes have jointly promoted the vigorous development of macrocyclic drug carriers in the biomedical field.For example,liposomes and micelles can be easily embedded in hydrophobic drug molecules,but their limited stability(micro-heterogeneous solutions cannot be stored for long periods)and lack of control over drug retention and release rates greatly limit their use as Wide use of drug delivery.Cucurbit[n]uril,as a new type of supramolecular host molecule,because of its good host-guest binding properties,they can both capture and release drugs,and can be adjusted by the size of the object and external stimulation.The ring usually exhibits high biocompatibility(such as biological inertness and low toxicity),making it widely used in drug delivery systems.In this paper,by studying the interaction of guarana with different degrees of polymerization and several anti-tumor drugs(adefovir,didanoxin,capecitabine,levofloxacin,etc.),this paper provides a certain degree of guarana in drug delivery.The theoretical basis of,the main research content and results are as follows:(1)The interaction between cucurbit[7]uril(Q[7])and adefovir(ADV)was studied in aqueous solution.The properties of Q[7]and ADV host and guest were explored by means of 1HNMR spectrum,UV absorption spectrum,isothermal calorimetric titration and mass spectrometry,and the results showed that the inclusion compound formed the inclusion of the purine ring portion of ADV,and the phosphonoformyl The oxyethyl group was left outside the cavity of the melon ring.The ITC data show that the complexity of this 1:1 inclusion formation is mainly driven by favorable enthalpy changes.Studies on the in vitro sustained release of inclusions and pure drug molecules,it was found that the released ADV of the study inclusion compound showed a faster rate under acidic conditions,although under the same conditions,the release of the inclusions was slower than that of the pure drug molecules.Thermal stability studies have shown that the inclusion form of ADV@Q[7]is more stable than the free ADV form.(2)Preparation of host-guest inclusion complexes of cucurbit[8]uril(Q[8])and levofloxacin(OFLX),and 1HNMR spectra,MALDI-TOF mass spectrometry,isothermal titration thermal analysis(ITC),fluorescence spectra,and UV-visible Characterize by absorption spectrum.These findings indicate that a host-guest inclusion complex can be formed by the methylmorpholine and piperazine rings of Q[8]inclusion OFLX molecule.ITC results show that the formation of this inclusion complex(molar ratio of 1:1)is mainly dependent on changes in enthalpy and entropy.In addition,OFLX is susceptible to release from the inclusion complex under acidic conditions,and its far rate is lower than that of pure drug molecules under similar conditions.(3)Utilizing the unique structure of melons(Q[n]s),they are the basic members of supramolecular organic framework.In this study,Q[8]was used as the basic building element,and a porous supramolecular assembly(Q[8]-PSA)based on Q[8]was prepared by simple crystallization in an aqueous HCl solution.The Q[8]-PSA is formed by the external surface interaction of Q[8]and the hydrogen bond between the lattice water molecule and the portal carbonyl oxygen of Q[8].Q[8]-PSA provides uniform pore structure,large specific surface area,and uniform pore size.It is characterized by single crystal XRD,TEM,SEM,and FT-IR spectra to obtain its morphology and structural characteristics.Thereafter,the Q[8]-PSA obtained was used to evaluate its adsorption performance for eight drugs of different shapes and sizes.In addition,controlled release of drugs in Q[8]-PSA was also investigated using orbital shakers at p H=4.5 and 6.8.(4)A simple and effective fluorescence enhancement method was demonstrated for the selective recognition and determination of the amino acids phenylalanine(Phe)and tryptophan(Trp).1HNMR spectrum shows that berberine hydrochloride(B~+)can be encapsulated in the seven-membered guar ring,eight-membered guar ring,and ten-membered guar ring(Q[7],Q[8],Q[10])in aqueous solution It forms stable 1:1,1:2,1:2 host-guest inclusion body complexes and exhibits moderate intensity fluorescence characteristics.Interestingly,the addition of Phe to Q[7]@B~+significantly reduced the fluorescence intensity of the inclusion complex;the addition of Phe to Q[8]@B~+significantly enhanced the fluorescence intensity of the inclusion complex;the addition of Trp to Q[10]@B~+significantly reduced the fluorescence intensity of the inclusion complex.In contrast,the addition of any other natural amino acid does not produce a change in fluorescence.According to the linear relationship between the fluorescence intensity and the concentration of Phe and Trp,the concentration of Phe and Trp in the target aqueous solution can be easily detected.Therefore,a new fluorescence method for identifying and determining Phe and Trp was established.