Fabrication Of Mesoporous Silica Based Drug Deliver System And Research Of Its Pharmacokinetic

Within the recent decades,mesoporous silica nanoparticles(MSN)became attractive in controlled release fields.By modifying the silicon hydroxyls,the drug release behaviors will be improved obviously.This dissertation carries out studies on the pH-responsible MSN/drug systems targeting the treatment of hypertension following physiological rhythms by molecular simulation and traditional experiments.At last,using spontaneously hypertension rat as hypertension model rats,an optimized delivery system was orally administrated to study the pharmacokinetic.So the dissertation is divided into the following several parts:1.MSN with an average pore size of 15 nm and different amounts of amino groups on pore surface were chosen as the models for simulation and metoprolol tartrate was chosen as the model drug under different releasing media.Results indicated that the MSD did not change significantly alongside the increase in the amounts of amino groups,but the chemical groups and the release media could affect the release behaviors of metoprolol tartrate.2.To study the effects of different modified systems on drug release performances,KIT-6 mesoporous silica and MPT were chosen as silica sample and target drug respectively and all systems are measured in both PBS and SGF.Results showed that the amino-modified system was able to achieve sustainable release for 24 h in both media,while an initial burst release was observed.To solve this problem,the pH-sensitive polymer PAA is introduced to coat the amino-modified drug loaded system.The result accorded with our expectation.3.To investigate the ability of MSN in controlling release of poorly water soluble drugs,NIF and KAN were chosen as model drugs.In-vitro release experiments were carried by using the PBS and the SGF as the media.For NIF/MSN systems,results revealed that solubility of NIF was not the main factor to decide its release behavior form MSNs.However,for the KAN/MSN systems,release percentages for all the systems were less than 20%in SGF,while long-term release of KAN was detected in the weak PBS,indicating interaction between MSN and KAN and the solubility of KAN played important roles in deciding its release behaviors.The results of molecular simulation corresponded with traditional experiments'4.the PAA coated amino-modified MSN/MPT controlled release system was selected to implement the in-vivo experiment.Results showed the PAA-NH2-KIT@MPT possesses relatively excellent ability for controlling release MPT.However,further work is still necessary to improve the design in order to minimize the possible release of MPT before it reaches the intestine.