Controlled Synthesis Of The Mesoporous Carbons With Tailored Morphologies And The Study Of Poorly Water Soluble Drug Release

Biopharmaceutics classification system II（BCSⅡ）drugs with low solubility in water,resulting in low oral bioavailability,which limits the clinical application.Recently,a new carrier material mesoporous carbon could solve the above problems.Rreducing the size of the drug to its nanoscale and changing the crystallization state of the drug were two effective means to increase its solubility and dissolution rate.The pore size of the mesoporous carbon is adjustable at 2-50 nm,which is matched with the size of the drug molecule.The characteristics of uniform pore size distribution,high specific surface area,large pore volume,no cytotoxicity,and biocompatibility good make mesoporous carbon as a good drug carrier.So that drug molecules could easily combine into the mesoporous channels,and turn to the highly dispersed state.Nano-channels can not only change the state of the drug from the crystal into amorphous but also can inhibit the recrystallization,thereby enhancing the drug solubility and dissolution rate.In this study,aqueous solution self-assembly method and one-pot method were used to synthesize mesoporous carbon with high specific surface area,large pore volume and tailored morphologies,including phenolic resin-based magnetic mesoporous carbon,phenolic resin mesoporous carbon and glucose-based mesoporous carbon.The morphology,porosity,melting point and crystal form of mesoporous carbon were investigated by scanning electron microscopy,nitrogen adsorption and desorption isotherm,thermal analysis and X-ray powder diffraction.The release of insoluble drugs in vitro was studiedwith selecting lovastatin,nifedipine and albendazole as drug models.The contents of this paper are as follows:（1）The magnetic mesoporous carbon nanospheres with different iron contents and different morphologies were synthesized by aqueous self-assembly method under acidic conditions,in which RF was used as carbon source,F127 as template and porogen,Fe（NO₃）₃· 9H₂O as magnetic source.The effect of the iron content and the spherical morphology was studied with the different time of adding the magnetic source.Firstly,when the magnetic source was introduced in the base solution,the content of Fe₃O₄ was up to 61.8%,and mesoporous carbon morphology was defected.Secondly,adding the magnetic source after 18 h,the amount of Fe₃O₄ was decreased（30.5%）but the spherical morphology of mesoporous carbon was relatively good.In the third condition,the original solution was removed by centrifugation after 18 h,and then introduced the magnetic source by dispersing with deionized water.The spherical mesoporous carbon was obtained and Fe₃O₄ content was 14.3%.The last was added the magnetic sources when the reaction is complete,after centrifugation,washing and drying calcination at 410 ℃.This method was the highest iron content up to 57.6%.Choosing magnetic mesoporous carbon as the carrier of lovastatin,the relaese results showed that the magnetic mesoporous carbon could significantly improve the release rate and release of lovastatin.The release process was fitted by the First-order empirical model and the coefficient association was 0.98.The MTT test data showed that the mesoporous carbon had no obvious cytotoxicity between the concentration of 0.1-1000 μg / mL and the biocompatibility was good.2.The synthesis of phenolic resin-based mesoporous carbon and the nifedipine release:Under acidic conditions,the controlled synthesis of mesoporous carbon（MCs）was achieved via the “SiO₂ assisted”.The mesoporous carbon with different pore size structures and morphologies were obtained using a one-pot method with phenolic resin as carbon source.The protonated phenolic resin could get facilitative access to the gap of the SiO₂ particles,due to the H-bonding interaction,capillary force,and the Coulombic interaction analogized to the "S+X-I+" mechanism under acid condition.The formation mechanism of mesoporous carbon morphology and pore structure porosity were investigated by SEM,BET,PSD and Zeta potentials.The morphology of the mesoporous carbon were changed from irregular bulk,spheres to apple-like morphology and the pore shape from ink-bottle-like to slitlike pores by varying the amount of SiO₂ from 0.5 to 3.0 g.The amount of SiO₂ particles had a great impact on the pore structure and morphology,indicating that the SiO₂ particles are not only the traditional porogen but also morphology control agent.Mesoporous carbons with different morphology and different pore structure were selected as carriers of nifedipine to explore the release property.Apple-like mesoporous carbon not only has high specific surface area,large pore volume,but also significantly improves the release and release rate of nifedipine,and the release behaviors were fitted by the exponential equation function.3.The one-pot synthesis of glucose-based mesoporous carbon and albendazole release:the different morphologies of mesoporous carbon were synthesis by one-pot method with glucose as carbon source,SiO₂ particles as porogen and morphology control agent.The amount of carbon source played an important role in pore structure and morphology.Albendazole as a model drug was loaded into the mesoporous channel of mesoporous carbon.Its physical states were changed from the crystalline form to an amorphous state.The solubility and release behaviors were significantly improved.The drug release results were fitted by the Weibull equation,and the fitting parameters were varied with the change of morphology.MTT method test was used to study the cytotoxicity of mesoporous carbon,and the result showed that mesoporous carbon has no obvious cytotoxicity between the concentration of 0.1-1000 μg / mL,which indicating the good biocompatibility of mesoporous carbon.In general,the above experimental datas have proved that using mesoporous carbon as a carrier of insoluble drugs could significantly improve the solubility and release rate by controlling the size and crystal state of drug.MTT method test was used to study the cytotoxicity of mesoporous carbon and biocompatibility.Selecting mesoporous carbon as a drug carrier provided a new idea and laid the experiment foundation for the future development.