- 學位論文
利用氫氧基磷灰石為藥物載體長效釋放薑黃素來預防肌少症
Curcumin-Loaded Hydrophobic Surface-Modified Hydroxyapatite as an Antioxidant for Sarcopenia Prevention
摘要
肌少症是一個會隨著年齡老化而伴隨肌肉量減少以及肌肉功能衰退之疾病。有鑑於目前治療肌少症的方式有許多副作用及效果不明顯之問題，希望能經由藥物釋放之系統來預防或治療早期肌少症的產生。薑黃素能降低肌肉發炎反應，對人體的毒性低，且副作用小。但薑黃素的口服利用率低，因此需要發展一個能乘載薑黃素的藥物載體。而氫氧基磷灰石有著良好的生物相容性，能透過控制藥物釋放的方式減少所需施打藥物的次數及頻率。因此本研究利用表面改質後之氫氧基磷灰石作為藥物載體乘載薑黃素來治療及預防早期肌少症。 在本研究中，使用共沉澱法合成氫氧基磷灰石，再利用硬脂酸進行表面改質，最後利用物理吸附乘載薑黃素(Cur-SHAP)。經由材料分析結果顯示，氫氧基磷灰石能有效乘載薑黃素，乘載量達 17.6%。合成的 Cur-SHAP 顆粒的大小為 500 到 1500 nm，這是細胞吞噬的適合大小。此外經由薑黃素釋放曲線能證明薑黃素能完全釋放並從endosome/lysosome複合物中逸出。細胞實驗中，證實Cur-SHAP 具有良好的生物相容性、抗氧化作用與抗發炎作用。動物研究的結果表明，利用LPS 誘導產生肌少症之大鼠，經由Cur-SHAP 治療後大鼠的肌肉耐力、握力和脂肪/瘦肉質量比均得到改善。綜合上述結果，我們成功合成疏水表面改質之氫氧基磷灰石，能有效乘載薑黃素並且藉由 IM 途徑給藥後，能有效減緩肌少症，在肌少症之早期治療與預防中具有應用潛力。
並列摘要
Oxidative stress and later-induced chronic inflammation have been reported to play an important role on the progression of sarcopenia. Current treatments for sarcopenia are mainly administered to patients who have developed sarcopenia. However, there has been no promising results shown in therapy. Therefore, the development of therapeutic and preventive strategies against sarcopenia would be necessary. Curcumin is a traditional medicine that possesses anti-inflammatory and antioxidative properties. In the present study, hydroxyapatite was subjected to hydrophobic surface modifications for curcumin loading (Cur-SHAP). It was, subsequently, utilized for delivery to the patient’s body via intramuscular injection in order to achieve constant release for more than 2 weeks, preventing the progression of the sarcopenia or even leading to recovery from the early stage of the illness. According to the results of WST-1, LIVE/DEAD, DCFDA, and gene expression assays, Cur-SHAP exhibited good biocompatibility and showed great antioxidant/anti-inflammatory effects through the endocytic pathway. The results of the animal studies showed that the muscle endurance, grip strength, and fat/lean mass ratio were all improved in Cur-SHAP-treated rats from LPS-induced sarcopenia. In summary, we successfully synthesized hydrophobic surface modification hydroxyapatite for curcumin loading (Cur-SHAP) and drug delivery via the IM injection. The LPS-induced sarcopenia rats were able to recover from disease after the Cur-SHAP treatment.