Study On The Construction And Properties Of Sustained Release Drug Based On Amino Acid Derivatives For Anti-Schistosoma Japonicum Cercariae

The Schistosomiasis Japonicum remains a hazardous and widespread parasitic disease in southern area of China.Thus elimination of schistosoma japonicum cercariae is an important way for prevention and treatment of schistosomiasis.Because most of the cercariae float on water and the complex surroundings,the urgent problem is long-term therapeutic of pesticides.Supramolecular hydrogel has been widely used in the field of drug release because of its good biocompatibility,low toxicity and biodegradability.In this theis,three types of drug delivery system based on supramolecular hydrogel were constructed by the self-assembly,which include three-component supramolecular hydrogel,single-component supramolecular hydrogel and supramolecular hydrogel based on drug molecule.The intrinsic properties of these supramolecular hydrogels were studied by various characterization methods.Further experimental results indicated that these drug delivery systems show good drug-release properties in the water environment.The main content and results are as follows:1)A three-component supramolecular gel based on alanine derivatives,melamine and riboflavin was prepared by self-assemble via hydrogen bonding and?-?interaction,which has been proven through scanning electron microscopy?SEM?and Fourier transform infrared?FT-IR?spectra.The rheological experiments showed that the hydrogel materials and drug-loaded hydrogel all demonstrated good mechanical strength and high stability.Further experimental results indicated that the drug-loaded hydrogels show large drug loadings?200 mg/m L?,long-term release time?10 days?and relatively higher efficiency for anti-cercariae in the water environment.2)A single-component supramolecular hydrogel based on the aspartic acid derivative N,N'-diaspartate-3,4,9,10-perylene tetracarboxylic acid imide?NAAPD?was constructed by convenient ultrasound method.The formation of hydrogel may be attributed to self-assemble via hydrogen bonding and?-?interaction,which have been researched using scanning electron microscopy?SEM?,UV,IR,fluorescence and XRD et al.This hydrogel showed excellent mechanical properties and good biocompatibility by rheological research and cytotoxicity test.As the anti-schistosoma japonicum cercariae drug-loaded material,the single-component hydrogel exhibits large drug loadings?500 mg/mL?,15 days long-term release time and 80%drug release rate in release process.This drug release system showed practical application potential due to its relatively higher efficiency in anti-cercariae experiment.3)The pharmaceutical dosage form of anti-cercariae drug cercariae niclosamide derivatives?NMD?was regulated.Two kinds of hydrogel release system were prepared with the modified NMD molecules,which are NMD?n=4?-EtOH-H₂O?V/V=4:6?thermo reversible hydrogel and NMD?n=4?-DMSO-H₂O?V/V=1:1?ultrasound hydrogel,respectively.The NMD hydrogels are assigned to typical physical gel.The microstructure of the hydrogels shows fibrous,which is attributed to be hydrogen bonding as the main driving forces in self-assemble process.The two hydrogels all show good mechanical properties and stability by rheological research.Delightfully,two hydrogel systems have extraordinary drug release ability,with more than 250h release time and 75%release rate,the mechanism of sustained-release meet Fickian diffusion law.