Preparation And Evaluation In Vitro Of Magnetic Drug-loaded Microspheres Targeting To Liver Tumour Cells

It is well known that traditional chemotherapy has the low therapeutic index and poor patients compliance. Targeting therapy for solid tumors, by specific guiding carriers to selectively locate anticancer drugs to tumors may increase the effective concentration of the drug in the required sites. Such an approach would dramatically achieve the anticancer drugs therapeutic efficacy, and reduce toxic side effects of drugs and promote the patients compliance.In the present study, the immunomagnetic doxorubicin-loaded microspheres (IMDM) designed to act as doxorubicin (DOX) carriers, which could be effectively delivered to solid tumors via intravenous administration. IMDM with magnetic targeting and specific targeting functions, were obtained by a reverse phase microemulsion process. Magnetic doxorubicin loaded alginate microspheres(MDAM) with the sizes of 100-300nm were prepared by heptane as organic dispersing medium and AOT as surfactant , then calcium ion as cross-linker, and the monoclonal antibody(Hab18), as specific targeting agent to human liver tumour cells, was conjugated to the MDAM by a l-Ethyl-3-(3-dimethyl-aminopropyl)carbodiimidehy-drochloride (EDO -introducing crosslinking reaction.The effects of preparation conditions such as the concentrations of ALG and surfactant, antibody dosage and reaction time of antibody with microspheres on IMDM properties, were investigated.by transmission electron microscopy, laser light scattering detector, atomic adsorption spectroscopy ,magnetic response test, and flow cytometer for the immunological activity of antibody on IMDM ,and ELISA for the evaluation of the specific combination between IMDM and human liver tumor SMMC-7721 cells. Results showed that:the spherical IMDMs had an average size of about 171.2nm, and most size distributions between 100nm and 300nm. IMDM loaded 108ug/mg of DOX, and released the drug in an effect concentration for a long time. IMDM also had a good magnetic response, and the antibody on the surface of IMDM was active and could guide the particles combined with human liver tumor cells. It was concluded that as a new carrier of DOX, IMDM could be used to effectively deliver DOX to the tumor by guidance of its magnetic targeting and antibody specific targeting in an effective theraptic concentration of DOX in the tumor and less side effects on the heart and the kidney. In summary, this study...