Protoapigenone固體脂質奈米顆粒劑型之處方設計及評估

Formulation design and evaluation of solid lipid nanoparticles loaded with protoapigenone

謝宜臻(Yi-Chen Hsieh)

指導教授 ： 黃耀斌

高雄醫學大學/藥學院/藥學研究所/碩士(2010年)

https://doi.org/10.6832/KMU.2010.00153

摘要

近幾年來，奈米劑型因具有發展成藥物輸送載體的潛力而倍受矚目；此外，很多研究顯示solid lipid nanoparticles（固體脂質奈米顆粒劑型，SLN）更結合其他奈米製劑之優點，本篇研究主要探討利用SLNs 劑型進行protoapigenone之處方設計及評估。Protoapigenone屬於一種新穎的類黃酮（flavonoids）成分，由Thelypteris torresiana（Gaud.）Alston，（粗毛金星蕨、大金星蕨）中分離出來，外觀為一淡黃色粉末，在細胞毒性試驗中已被證實對於人類的肝癌（HepG2、Hep3B）、乳癌（MDA-MB-231、MCF-7）及肺癌（A549）細胞都有良好的抑制效果。實驗過程中先找出最佳分析組成條件（0.1 M ammonium acetate buffer containing 0.27 mM EDTA：ACN＝62：38），並選用不同組成之處方，評估其粒子大小、表面電位、包埋率及安定性等物理化學性質，經由這些參數可得到一最佳化處方：TM+53/10，透過穿透式電子顯微鏡（TEM）評估處方外觀。腹腔注射給予protoapigenone SLNs 10 mg/kg於健康小鼠，並與其溶液劑作比較，兩者皆經過固相萃取步驟後以LC-MS/MS分析。結果發現SLNs組別濃度略高於溶液劑，在統計上並無顯著性差異，此外也進行其在小鼠體內臟器分佈之評估，結果顯示在肝臟有較高之藥物分佈。

關鍵字

Protoapigenone ； SLN ； solid-phase extraction ； LC-MS/MS

並列摘要

In recent years, lipid nanospheres have been attracted great interest because of their potential application in medicine as drug delivery carriers. Moreover, many researches pointed out that the solid lipid nanoparticles (SLN) combine the advantages and avoid the disadvantages of other colloidal carriers. The purpose of this study was to prepare and evaluate of solid lipid nanoparticles loaded with protoapigenone in vitro study. Protoapigenone, a kind of flavonoid, was isolated from Thelypteris torresiana (Gaud), Alston, which showed potent cytotoxic activity against HepG2 and Hep3B (liver), MDA-MB-231 and MCF-7 (breast), and A549 (lung) human cancer cell lines. In this study, we fount out the optimized of condition (0.1 M ammonium acetate buffer containing 0.27 mM EDTA：ACN＝62：38). We utilized the protoapigenone as an indicated ingredient and determined the stability, size distribution, zeta potential, and entrapment efficiency to compare with different formulations, we fount out the best formulation was TM+53/10. The morphology of the protoapigenone SLNs was examined by transmission electron microscopy (TEM). After intraperitoneal administration of protoapigenone SLNs, compared with protoapigenone solution, based on solid-phase extraction (SPE) and analysis by LC-MS/MS. The result showed that there was no significant difference in the two groups. It was found that the content of tissue was higher amount in the liver than the other organ tissue.

並列關鍵字

Protoapigenone ； SLN, ； solid-phase extraction ； LC-MS/MS

參考文獻

[1] P. M. D. Angelis, L. Mancinelli, L. Annulli, K. Elgjo, V. Padovini, G. L. Gianfranceschi, A class of DNA-binding peptides from wheat bud causes growth inhibition, G2 cell cycle arrest and apoptosis induction in HeLa cells, Molecular Cancer, 8 (2009) 55-65.

[2] D. Raulet, S. Gasser, The DNA damage response, immunity and cancer, Seminars in Cancer Biology, 16 (2006) 344-347.

[3] E. K. Kranenbarg, J. Hermans, JHJM van Krieken, CJH van de Velde, Evaluation of the 5th edition of the TNM classification for gastric cancer: improved prognostic value, British Journal of Cancer, 84 (2001) 64-71.

[4] D. Atmani, N. Chaher, D. Atmani, M. Berboucha, N. Debbache, H. Boudaoud, Flavonoids in Human Health: From Structure to Biological Activity, Current Nutrition & Food Science, 5 (2009) 225-237.

[5] B. M. Rezk, G. R. M. M. Haenen, W. J. F. van der Vijgh, A. Bast, The antioxidant activity of phloretin: the disclosure of a new antioxidant pharmacophore in flavonoids, Biochemical and Biophysical Research Communications, 295 (2002) 9-13.