開發穿心蓮內酯奈米乳劑之經皮傳輸劑型並以風濕關節炎動物模式評估其抗發炎效果

Development of andrographolide-loaded nanoemulsion transdermal delivery system and evaluation of anti-inflammatory effect on animal model of rheumatoid arthritis

鄭釗沛(Chao-Pei Cheng)

指導教授 ： 吳育澤

高雄醫學大學/藥學院/藥學系碩士班/碩士(2019年)

摘要

穿心蓮內酯於臨床試驗中被證實對於關節發炎疾病具有治療效果。然而，穿心蓮內酯因其水溶性差以及易遭遇首渡代謝而造成口服吸收不佳，本研究之目標擬開發穿心蓮內酯經皮吸收之奈米乳劑，作為治療關節發炎之新劑型。依據溶解度試驗之結果，選擇Capryol-90作為溶解穿心蓮內酯之油類，乳化劑為Tween 80、輔助乳化劑為Transcutol P，經磁石攪拌和高速均質法製成奈米乳劑，並偵測穿心蓮內酯於3個月內安定性試驗之含藥量及粒徑大小，以及使用垂直式經皮吸收擴散槽優化最適之處方。經由本次實驗優化最適配方之24小時穿透度結果可達到約14 (w/w)的穿透量，平均液滴尺寸為18010 nm (n=3)，在為期3個月室溫安定性試驗環境下足以維持98以上的穿心蓮內酯含量，皮膚刺激性試驗中，觀測最適配方無明顯破壞皮膚之角質層及表皮層，對於大鼠皮膚產生較少之刺激。於注射鹿角膠誘發風濕性關節發炎之大鼠模式中，和對照組相比，塗抹此配方能降低腳部腫脹28體積。因此本研究所開發之穿心蓮內酯奈米乳劑可提升主成分的含藥量至2.5 mg/mL及28倍之穿透皮膚的含量，並由初步的動物模型之結果顯示，穿心蓮內酯奈米乳劑具有抗發炎的潛力。

關鍵字

穿心蓮內酯 ； 奈米乳劑 ； 經皮吸收 ； 關節炎

並列摘要

Andrographolide has been confirmed to have a therapeutic effect on joint inflammatory diseases in clinical trials. However, owing to it poor water solubility and suffering from a lot of first-pass metabolism, the oral absorption of andrographolide is quite low. Therefore, in our study, I developed the nanoemulsion and transported by transdermal delivery system. This technology is considered as a new pharmaceutic for therapy of arthritis. According to the result of solubility test, I selected Capryol 90, Tween 80 and Transcutol P as the oil, surfactant and co-surfactant for the composition of nanoemulsion and then prepared by magnet stirring and high speed homogenization. The particle size and drug loading were also analyzed during 3 months stability test. The formulations were evaluated by vertical percutaneous absorption diffusion cell to select the optimal formulation. In the permeability test, the andrographolide passed through the skin of rat is up to 14 (w/w) within 24 hours. The droplet size of optimal formulation is 18010 nm (n=3) and could sustain 98 drug loading during 3 months stability test. In skin irritation test, the stratum corneum and epidermis weren’t destroyed by the optimal formulation obviously during 24 hours and improved has less irritation on the rat skin. On the model of carrageenan-induced arthritis rats, compared with controlled group, the optimal formulation could reduce 28 swelling volume of the foot. Therefore, in my study, the andrographolide loaded nanoemulsion can improve not only the drug loading to 2.5 mg/mL but the rate of permeability to 28 folds in andrographolide. Ultimately, in the preliminary results of the animal model, andrographolide loaded nanoemulsion has the potential on the effect of anti-arthritis.

並列關鍵字

Andrographolide ； nanoemulsion ； transdermal delivery system ； arthritis

參考文獻

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