以黃原膠為基材製備微粒作為腎臟癌之新型藥物載體

黃原膠是由黃單胞菌（Xanthomonas campestris）所產生，為陰離子、高分子量的細胞外多醣。它的結構由葡萄糖，甘露糖和葡萄醣醛酸組成。而在生物醫學應用因具有出色的流變性，可溶於水並在低濃度下產生高黏度，作為增稠劑，懸浮劑和乳液穩定劑。Sunitinib malate (Sutent)是腎細胞癌的第一線用藥，為多酪氨酸酶抑制劑且伴隨許多副作用，包括疲勞，手足綜合症，甚至危及生命的心臟毒性。因此，為了克服這些缺點，透過乳液聚合交聯製備黃原膠微粒作為藥物遞送系統的載體，以減少系統毒性並改善癌舒特的臨床應用。與各種製備條件與變相（例如膠濃度，油水比，鹽濃度和交聯劑濃度）有關。黃原膠微粒的平均粒徑分別為229.2, 142.4, 30.45μm. 經此研究顯示具有血液相容性，在不同粒徑下溶血百分比分別為0.9%, 0.6%, 2.0%. 此外，黃原膠微粒在纖維母細胞存活率高於70％，顯示黃原膠微粒具有生物相容性且無毒。而裝載Sutent的黃原膠微粒對A498細胞毒性較低。且包覆癌舒特之黃原膠微粒符合Higuchi釋放動力學模型，本研究旨在以乳化聚合交聯方法製備以黃原膠為基材之微粒，期許在未來能做為腎細胞癌之新型藥物載體。

Xanthan gum is anionic, high molecular weight, exopolysaccharide produced by Xanthomonas campestris. Its basic chain consists of glucose, mannose, and glucuronic acid. Biomedical applications of xanthan gum are based on its exceptional rheological properties, which is soluble in water and produces high viscosity at low concentration. It is used as thickening agent, suspending agent, and emulsion stabilizer. Sunitinib malate is first-line multi-targeted tyrosine inhibitor for renal cell carcinoma. Sunitinib malate (Sutent), is associated with many side effects, including fatigue, hand-foot syndrome, even life-threatening cardiac toxicity. Therefore, to overcome these disadvantages, this study is to prepare microspheres of xanthan gum-based materials for carriers of renal cell carcinoma. Designing xanthan gum microspheres by emulsion aggregation cross-linking aims to be carriers of drug delivery system in order to reduce systematic toxicity and improve clinical use of sunitinib. The effect of various formulation and process variables such as gum concentration, oil-water ratio, salt concentration, and cross-linking agent concentration. The average particle size of xanthan gum microspheres is 229.2, 142.4, 30.45 μm at respectively screen mesh. Xanthan gum microspheres is considered hemocompatible by with hemolysis percentage 0.9%, 0.6%, 2.0% at respectively screen mesh. Besides, xanthan gum microspheres show no toxicity in vitro fibroblast survival rate behind 70%. Xanthan gum microspheres are found biocompatible and non-toxicity. Sunitinib-loaded xanthan gum microspheres show low toxicity in A498 cell. Additionally, sunitinib-loaded xanthan gum microspheres correspond Higuchi release kinetics model with R square 0.9995, 0.9983, 0.9996 respectively. In conclusion, preparation microspheres of xanthan gum-based may be new drug delivery carrier of renal cell carcinoma in the future.