Sonochemical Preparation Of Tumor Targeting Reductive-responsive Carboxy-polysaccharide-based Microcapsules

In recent years,the intelligent drug delivery system has been attracted extensive attention from researchers because it combine targeted drug delivery ability and controlled drug release ability which can improve the loading efficiency,accurately deliver the drug to the pathological sites.Among them,the research on microcapsules has gradually deepened in which microcapsules can protect capsule core drugs better,maintain active ingredients and possess the properties of targeted drug delivery and triggered drug release.There are also many methods for preparing microcapsules,including in-situ polymerization,interfacial polymerization,spray drying,and sonochemical methods.Above them,the sonochemical method has been proved to be a facile,efficient and environment friendly method in which capsules synthesized by sonochemical possess uniform particle size distribution and no agglomeration.In this paper,functional polysaccharide-based microcapsules were prepared by sonochemical method and their properties were further investigated.Two kinds of alginate-based microcapsules with magnetic targeting property and folate targeting property respectively were studied in this paper.The magnetic reduction-responsive alginate-based microcapsules（MRAMCs）loaded oleic acid-modified Fe₃O₄ and C6 that dispersed in the oil phase into the microcapsules.The folic acid targeted reductive-responsive alginate-based microcapsules（FA-RACMs）with FA molecules modified on the capsule walls could bind specifically to folate receptors on the surface of tumor cells.The research shows that they possess excellent magnetic targeting and molecular targeting respectively.Both of them could rupture the capsule wall and release the drug successfully under the environment of reducing agent and controlled release of drugs to tumor cells effectively.The folic acid targeted reductive-responsive carboxymethyl cellulose-based microcapsules（FA-RCMCs）with folic acid targeting and reduction responsiveness was prepared with folate-modified thiolated carboxymethyl cellulose.At the same time,C6,a hydrophobicgreen fluorescent dye,as the capsule core model drug,encapsulated inside FA-RCMCs and the capsule wall was formed by cross-linking sulfhydryl groups.The effect of preparation conditions on the particle size of FA-RCMCs,the morphology of the capsules,cell uptake and cytotoxicity experiments were further investigated,which proved that FA-RCMCs possess excellent biocompatibility and controlled release ability.FA-RCMCs would become a promising smart drug carrier.