Preparation And Sustained Release Properties Of Cellulose/chitosan Composite Drug-loaded Microsphere

It is estimated that millions of people are diagnosed with cancer every year,and the currently marketed anticancer drugs generally have disadvantages such as low delivery efficiency,short semi-life and high toxicity,which limit their routes of administration and clinical effectiveness.Slow and controlled release drug delivery systems(SCDDS)can effectively improve the bioavailability of drugs by controlling the rate of drug release and its direction of delivery.However,SCDDS has some drawbacks,which make the drug effect unstable in vivo.Therefore,it is especially important to develop carriers with high loading rate and excellent sustained release performance.Organic-inorganic composite sustained release materials have a broad application prospect in the field of sustained and controlled release because of their good biocompatibility,high drug loading rate and intelligent drug release.Chitosan gel,with an internal network structure,has received close attention in the sustained release of pentafluorouracil(5-Fu)because of its non-biotoxic properties,but there are problems such as low loading rate and sudden release effect.To solve this problem,three organic-inorganic composite gel microspheres(GO/HPC/CS@5-Fu,DE/HPC/CS@5-Fu,and SiO2/HPC/CS@5-Fu)were prepared by chemical cross-linking method using glutaraldehyde as the cross-linking agent in this thesis.These three composite drug-loaded microspheres were prepared by using chitosan and hydroxypropyl cellulose as organic substrates,followed by graphene oxide,diatomaceous earth and silica aerogel as fillers,respectively,and pentafluorouracil(5-Fu)as a model drug.The properties of these three microspheres were analyzed and the following conclusions were drawn:(1)The optimal organic raw material ratio in the composite gel microspheres was determined as m HPC/m CS = 3:2 by changing the feeding ratio of chitosan and hydroxypropyl cellulose and using the encapsulation rate and drug loading rate as the judgment criteria.Then,the in vitro sustained release performance of 5-Fu in composite drug-carrying gel microspheres with different amounts of inorganic fillers was investigated on this basis.The results of SEM,FI-IR,XRD,TG and DSC showed that three kinds of composite drug-loaded microspheres(GO/HPC/CS@5-Fu,DE/HPC/CS@5-Fu and SiO2/HPC/CS@5-Fu)were successfully prepared in this experiment,and these drug-loaded microspheres had good spherical morphology and porous structure with good thermal stability.(2)Secondly,both the drug loading rate(DL)and encapsulation rate(EE)experiments demonstrated that the addition of inorganic fillers had a certain degree of effect on both DL and EE of the composite drug-loaded microspheres.This may be related to the unique structure of inorganic fillers and the different active sites they carry: GO is prone to π-π stacking with 5-Fu,and the Si-OH group in DE and silica aerogels has been hydrogen bonded to the drug.In addition,in vitro sustained release experiments under different media(p H=1.2,5.0,7.4)illustrated that the addition of inorganic nonmetals could alleviate the sudden release of drugs to some extent.The optimal inorganic-organic filler ratio can be judged based on the best slow release effect.Moreover,the drug release of these three composite drug-carrying gel microspheres was p H-responsive.(3)Finally,in vitro sustained release experiments still showed a sudden release problem of 80% cumulative release of 5-Fu within 8 h.Therefore,the best sustained release composite gel microspheres were coated with Eudragit ?L100 by solvent evaporation to solve the problem of sudden release.The in vitro abrupt release of the coated modified composite gel microspheres was further improved.Moreover,the three different drug-loaded microspheres coated with Eudragit?L100 showed the best sustained release at three different p Hs(GO-7.4,DE-5.0,SiO2-1.2),so the different filler-derived drug-loaded systems can be used for chemotherapy of tumors at different focal sites.Finally,the four kinetic models of zero-order,first-order,Higuchi,and Korsmeier-Peppas were linearly fitted with the slow release data of 5-Fu,and the results showed that the three inorganically modified composite gel microspheres followed different kinetic models for the release of 5-Fu in different PBS.