Preparation Of Nanoparticle-loaded Controlled Release Tablets For Ultrasound Diagnosis And Treatment

Due to the unique characteristics for the diagnosis and treatment of local and systemic administration,nanoparticle was regarded as a promising diagnostic and therapeutic tool.Iron oxide nanoparticles are promising nanomedicine because of their superparamagnetic effect and excellent biocompatibility and biodegradability.Comparing with other dosage form,the oral administration of nanoparticles is gradually regarded as one of the most commonly used nanoparticle administration form because of its excellent patient compliance and convenience,as well as the high absorption.However,the factors affecting oral administration involves the solubility,stability and bioavailability of nanoparticles,as well as the acidic environment,mucosal structure and mucus secretion of stomach.There are still many obstacles to the oral nanoparticle drug delivery system.In this thesis,a nanoparticle-loaded drug controlled release tablet was designed and prepared.The tablets can generate carbon dioxide bubbles in situ in the stomach microenvironment.When further applied with the ultrasonic energy,the controlled release of nanoparticles and the promotion of drug absorption were achieved.The main research contents are as follows:(1)An in situ bubbles generated nanoparticle-loaded controlled release tablets was designed.One tablet weight was 200 mg with 871.00?g iron per tablet.The prepared tablets could be completely dissolved in an acidic environment after 6-7 h(HPMC as the adhesive ingredient)and 10-12 h(HPMC/Carbomer(1:1)as the adhesive ingredient)to produce carbon dioxide bubbles,which can be imaged by ultrasound contrast imaging in real-time.Meanwhile,the dissolution release of the tablets was characterized by transmission electron microscopy(TEM),vibrating sample magnetometer(VSM),ultraviolet spectrophotometer and magnetic resonance imaging(MRI).The feasibility of loading nanoparticles into a tablet was proved,and the dissolution profiles and rate of the iron content of the tablet in an acidic environment were demonstrated.The nanoparticles were not completely released into the solution at the room temperature(25?)since they were retarded in the dissolved adhesive material dispersed in solution,the final dissolution rates of the iron content of the tablet were 87.31%and 63.65%.And it can be promoted to over 88.37%in 37?environment.(2)The dissolution release morphology of the tablets was characterized by TEM and MRI after treated by ultrasound(0.5,1.0,1.5,2.0 and 2.5 W/cm~2)The results show that the movement of tablets can be controlled by ultrasound due to the bubble generation,and the moving speed would be accelerated with the increase of the ultrasonic energy.Compared with the control group without ultrasound exposure,the tablets were completely dissolved within 1.5 h(HPMC as the adhesive ingredient)and 4 h(HPMC/Carbomer(1:1)as the adhesive ingredient)when applied with 2.5 W/cm~2 ultrasound.The dissolution rates of iron content were promoted by ultrasound energy from 43.60%and 48.04%of incompletely dissolved tablets to almost 100.00%.(3)Finally,the pig stomach ex vivo experiment was performed with the 2.5 W/cm~2ultrasound treatment for 1.5 h.The pathological section result showed that for the control group without ultrasound treatment,the nanoparticles were mainly accumulated in the mucosa layer of tissue,while for the test group applied with 2.5 W/cm~2 ultrasound,the nanoparticles were pushed into the muscle layer of tissue.Therefore,it was proved that ultrasound could promote the nanoparticles delivery in the tissue.