Preparation And Properties Of Hollow Mesoporous Organosilicon Nano-microparticles And Its Composite Hydrogels

Drug controlled release has many advantages such as high therapeutic effect,low dosage and so on.It is vital that to improve the comprehensive performance of drug delivery carrier,to optimize the performance of controlled release,and to broaden the applicated fields,et al.To solve the disadvantage of traditional drug delivery carrier,hollow mesoporous nano-silicone composite hydrogel was prepared and in vitro drug release behavior was investigated.This kind of hydrogel not only can be used as a drug delivery carrier for small molecule drugs and/or protein drugs,but also can be used in drug controlled release for different types of drugs jointly.1.The nanoscale SiO₂ nuclear was obtained by using the tetraethyl orthosilicate?TEOS?as the source of silicon and by using the ammonia as the alkaline reagent in the mixed solvent of ethanol and water.The cetyl trimethyl ammonium chloride was used as template agent and bis[3-?triethoxysilyl?propyl]tetrasulfide was uesd as the source of organic silicon to form disulfide bridge mesoporous materials which can be coated on the surface of nano-SiO₂ like a shell.The nano-SiO₂ nuclear was etched by Na₂CO₃aqueous solution,and the hollow mesoporous organosilicon nano-microparticles?HMON?was finally obtained.The morphology of HMON was characterized by FESEM and TEM,its drug-loading ratio,coating ratio,and drug release behavior for7-Ethyl-10-hydroxycamptothecin were evaluated.The results indicated that the particle size of nano-SiO₂ can be controlled at 80⁵00 nm by changing the content of water,the dropping speed of TEOS,and reaction temperature.The particle size of SiO₂@MON varying from 200 to 350 nm can be obtained via changing the dosage of BTES and reaction temperature.The coating ratio is 74.65%,the drug-loading ratio is 24.88%and the cumulative release percentage is 81%after 6 d for 7-Ethyl-10-hydroxycamptothecin from drug-loaded HMON when its average grain diameter is 150²00 nm,specific surface area is 157.16 m²·g^-1and total pore volume is 0.35 cm³·g^-1.2.The natural high polymer hyaluronic acid?HA?and carboxymethyl cellulose?CMC?was modified by cystamine dihydrochloride respectively,and then HA-SH and CMC-SH were prepared by DL-dithiothreitol?DTT?.A series of HA/CMC hydrogels were prepared by oxidation of free thiol groups between HA-SH and CMC-SH themselves and each other to form disulfide bond.The gelling time,rheological properties,swelling ratio,degradation percentage and in vitro drug release behavior were investigated.The research results showed that the gelling time of the hydrogels was about 1.4⁷.0 min indicating these hydrogels can be used in injection field.In addition,the swelling and degradation research in PBS solution of these hydrogels showed that HA/CMC hydrogels can be fast swelled with high swelling ratio and good stability,the swelling ratio of HA3/CMC3 was up to 33 in 12 h,and the degradation percentage was only 40.80±1.80%for 42 d.The drug-release research results showed that all HA/CMC hydrogels can achieve the effectively controlled release for BSA and 7-Ethyl-10-hydroxycamptothecin,and the best result was from HA3/CMC3 hydrogel.3.The HMON were modified by?3-shpropyl?triethoxy silane to obtain HMON-SH,then the nanocomposite hydrogels?HMON-SH@HA/CMC?were prepared with the formation of disulfide bond?-S-S-?by chemical cross-linking between HMON-SH,HA-SH,and CMC-SH themselves and each other.The microstructures,swelling and degradation behaviors,the drug release behaviors of the series of composite hydrogels were investigated.It was founded that the equilibrium swelling ratio of5HMON-SH@HA1/CMC1,5HMON-SH@HA2/CMC2,5HMON-SH@HA3/CMC3,3HMON-SH@HA3/CMC3 and 1HMON-SH@HA3/CMC3 were about 38.26±1.30,34.75±1.08,29.93±0.78,30.50±0.51 and 31.66±0.50,respectively,and their degradation percentage were about 38.01±1.36,31.71±2.05,19.81±2.03,40.11±1.61and 45.22±0.69%after 42 d,respectively.On the 15th d,the cumulative release percentage of 7-ethyl-10-hydroxy-camptothecin in joint drug loading system from5HMON-SH@HA3/CMC3+B+C,3HMON-SH@HA3/CMC3+B+C,and1HMON-SH@HA3/CMC3+B+C were about 57.83±0.95,61.14±3.37 and 62.48±3.14%,while for BSA were about 75.60±0.90,78.05±0.51,80.51±1.01%,respectively.In summary,HMON-SH@HA/CMC composite hydrogels have good capability of drug loading alone and synergistic drug loading,and can be potentially used in drug delivery and other fields.