臺灣博碩士論文加值系統

植物活性物質 (Phytochemicals) 對於促進健康、預防及治療疾病擁有極大的潛力，但由於低溶解度、低穩定度、低生體可用率及低標靶專一性的限制，無法廣泛地在臨床上應用。本實驗使用薄膜水合法製備自組型卵磷脂混合型微胞，結合卵磷脂與多種兩性物質 (如：TPGS, Pluronic®, Cremophor®, Sodium deoxycholate (NaDOC) ) 作為植物活性物質 (薑黃素、和厚朴酚/厚朴酚、白藜蘆醇) 載體，篩選最佳化之藥物傳遞系統及探討比較不同比例之卵磷脂與不同兩性物質對微胞形成之影響，以及改善植物活性物質溶解度及生體可用率。
本研究利用薄膜水合法製備混合型微胞，開發出兩個系統，一個為NaDOC與卵磷脂組成，利用此系統包覆薑黃素與和厚朴酚/厚朴酚，最佳處方比例為活性成分、卵磷脂與NaDOC分別為2:1:5與6:2:5，粒徑大小分別為111.6 ± 4.24 (PI = 0.327±0.021) 與147.1 ± 31.11 (PI = 0.052±2.137) nm，藥物負載率分別為26.3及44.4%，而藥物包覆率皆在95%以上。另一個系統則為Pluronic® P123與卵磷脂形成的混合型微胞，此系統可以包覆四種植物活性物質 (薑黃素、和厚朴酚/厚朴酚、白藜蘆醇)，活性成分、卵磷脂與Pluronic® P123最佳比例分別為5:2:20、1:1:10及5:2:20 ，粒徑大小為143.1 ± 1.72 (PI = 0.654±0.032)、177.5 ± 39.97 (PI = 1.118±0.063) 與132.2 ± 9.62 (PI = 1.297±0.255) nm，藥物負載率分別為16、9.8及19.3%，而藥物包覆率皆在85%以上。兩種藥物傳遞系統皆將植物活性物質的水溶解度提升至6 mg/ml。
其中使用NaDOC形成的微胞其藥物負載率較高且PI值較小，表示粒徑分布範圍會比較狹窄，在體外釋放實驗中顯示有速放的效果，而Pluronic® P123之包覆系統在體外實驗中具有緩釋效果，且適量增加卵磷脂的含量會促進其包覆率上升。在儲存安定性方面，除了薑黃素微胞僅能在室溫下儲存14天，在包覆和厚朴酚/厚朴酚與白藜蘆醇中皆可在室溫儲存長達56天以上。而在血漿中的穩定性則可以發現，雖然Pluronic® P123混合型微胞較容易受血漿蛋白影響，但其穩定性會優於NaDOC混合型微胞，證明高分子微胞穩定性比傳統界面活性劑微胞佳。在大鼠實驗中靜脈注射混合型微胞Curcumin、Honokiol-Magnolol，可將絕對生體可用率提高至573、323及499%，而口服給予時，絕對生體可用率分別提高至2、8及31.8%，由此可知將植物活性物質製備為自組裝型卵磷脂混合微胞可以成功改善其生體可用率。

Phytochemicals have great potential for maintaining and promoting health, as well as preventing and potentially treating some diseases. However, the low solubility, stability, bioavailability and target specificity generally have limited clinical application. In this study, the solubility of four phytochemicals (Curcumin/Resveratrol/Honokiol-Magnolol) was in an attempt to be enhanced by encapsulating in self-assembly lecithin-based mixed micelles composed of lecithin and several amphiphilic material (TPGS/Pluronic®/Cremophor®/Sodium deoxycholate).
Self-assembly lecithin-based mixed micelles for phytochemicals were prepared by using thin film hydration method. Two mixed polymeric micelles containing lecithin and either amphiphilic materials Sodium deoxycholate (NaDOC) or Pluronic® P123 were found to be optimal to encapsulate curcumin, honokiol/magnolol, and resveratrol. The optimized ratios of mixed micelles containing lecithin and NaDOC were 2:1:5 and 6:2:5 (phytochemicals:lecithin:NaDOC). The particle size of these micelles were 111.6 ± 4.24 (PI = 0.327±0.021) and 147.1 ± 31.11 (PI = 0.052±2.137) nm, drug loading were 26.3% and 44.4%, and the encapsulation efficacy (E.E.) were all above 95%. Another optimal mixed polymeric micelles containing lecithin and Pluronic® P123 could encapsulate four phytochemicals (Curcumin / Honokiol & Magnolol / Resveratrol), the optimized ratios of this system were separately 5:2:20, 1:1:10 and 5:2:20. The particle size of each phytochemicals were 143.1 ± 1.72 (PI = 0.654±0.032), 177.5 ± 39.97 (PI = 1.118±0.063) and 132.2 ± 9.62 (PI = 1.297±0.255) nm, drug loading were 16%, 9.8% and 19.3%, and the E.E. were all above 85%. The solubility of NaDOC and Pluronic® P123 systems were all up to 6 mg/mL.
The mixed micelles formed by NaDOC had higher E.E. and narrower particle distribution. In vitro study indicated immediate-release profile. The mixed polymeric micelles containing Pluronic® P123 could improve E.E. with increasing the amount of lecithin and sustained release profiles were observed correspondingly. Regarding storage stability, the mixed micelles of both systems could be maintained stable up to 56 days at room temperature except those containing curcumin. In the serum stability test indicated that although the integrity of Pluronic® P123 mixed micelles might be affected by serum protein, it demonstrated to be more stable than the NaDOC system. In pharmacokinetics study, intravenous administration of the mixed micelles containing curcumin and honokiol-magnolol was found to significantly increase the absolute bioavailability to 573%, 323% and 499%, and oral administration of the mixed micelles could increase absolute bioavailability to 2%, 8% and 31.8%. It seems that this novel phytochemicals-loaded self-assembly lecithin-based mixed micelles can be used to improve their absolute bioavailabilities.

目錄 I
附圖目錄 III
附表目錄 VII
中文摘要 XI
Abstract XIII
第壹章、 緒論 1
第一節、 研究背景介紹 1
一、 微胞 3
二、 兩性物質 15
三、 植物活性物質 25
第二節、 研究目的 38
第貳章、 研究材料與實驗方法 39
第一節、 實驗材料 39
第二節、 實驗方法 40
一、 植物活性物質之高效液相層析法分析方法 40
二、 血漿中Curcumin之極致效能液相層析串聯質譜分析方法分析方法.. .. .. .. 44
三、 血漿中Honokiol與Magnolol之極致效能液相層析串聯質譜分析方法.. .. .... 48
四、 和厚朴酚及厚朴酚粉末含量測定 52
五、 溶解度試驗 52
六、 自發型微胞體粒子製備與評估 52
七、 安定性 55
八、 體外藥物釋放實驗 55
九、 大鼠體內之藥物動力學實驗 56
第參章、 結果與討論 61
一、 植物活性物質之高效液相層析法分析方法 61
二、 血漿中Curcumin之極致效能液相層析串聯質譜分析方法.. 72
三、 血漿中Honokiol與Magnolol之極致效能液相層析串聯質譜分析方法.. .. .. 77
四、 和厚朴酚及厚朴酚粉末含量測定 85
五、 溶解度試驗 85
六、 自發型微胞體粒子製備與評估 87
七、 穿透式電子顯微鏡 108
八、 安定性 110
九、 體外藥物釋放實驗 115
十、 大鼠體內之藥物動力學實驗 119
第肆章、 結論 132
第伍章、 參考文獻 134

1.Prabhu, S., M. Ortega, and C. Ma, Novel lipid-based formulations enhancing the in vitro dissolution and permeability characteristics of a poorly water-soluble model drug, piroxicam. International journal of pharmaceutics, 2005. 301(1-2): p. 209-16.
2.Savjani, K.T., A.K. Gajjar, and J.K. Savjani, Drug solubility: importance and enhancement techniques. ISRN pharmaceutics, 2012. 2012: p. 195727.
3.Torchilin, V.P., Micellar nanocarriers: pharmaceutical perspectives. Pharm Res, 2007. 24(1): p. 1-16.
4.Kalepu, S., M. Manthina, and V. Padavala, Oral lipid-based drug delivery systems – an overview. Acta Pharmaceutica Sinica B, 2013. 3(6): p. 361-372.
5.Torchilin, V.P., Structure and design of polymeric surfactant-based drug delivery systems. Journal of controlled release : official journal of the Controlled Release Society, 2001. 73(2-3): p. 137-72.
6.Owen, S.C., D.P.Y. Chan, and M.S. Shoichet, Polymeric micelle stability. Nano Today, 2012. 7(1): p. 53-65.
7.Zhao, X., Z. Poon, A.C. Engler, D.K. Bonner, and P.T. Hammond, Enhanced stability of polymeric micelles based on postfunctionalized poly(ethylene glycol)-b-poly(gamma-propargyl L-glutamate): the substituent effect. Biomacromolecules, 2012. 13(5): p. 1315-22.
8.Blanco, E., C.W. Kessinger, B.D. Sumer, and J. Gao, Multifunctional micellar nanomedicine for cancer therapy. Experimental biology and medicine, 2009. 234(2): p. 123-31.
9.Jones, M. and J. Leroux, Polymeric micelles - a new generation of colloidal drug carriers. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 1999. 48(2): p. 101-11.
10.Kaur, I.P. and H. Singh, Nanostructured drug delivery for better management of tuberculosis. Journal of controlled release : official journal of the Controlled Release Society, 2014. 184C: p. 36-50.
11.Kore, G., A. Kolate, A. Nej, and A. Misra, Polymeric Micelle as Multifunctional Pharmaceutical Carriers. Journal of Nanoscience and Nanotechnology, 2014. 14(1): p. 288-307.
12.Torchilin, V.P., PEG-based micelles as carriers of contrast agents for different imaging modalities. Advanced drug delivery reviews, 2002. 54(2): p. 235-252.
13.Rijcken, C.J., O. Soga, W.E. Hennink, and C.F. van Nostrum, Triggered destabilisation of polymeric micelles and vesicles by changing polymers polarity: an attractive tool for drug delivery. Journal of controlled release : official journal of the Controlled Release Society, 2007. 120(3): p. 131-48.
14.Myrra G. Carstens, C.J.F.R., Cornelus F. van Nostrum, Wim E. Hennink, Pharmaceutical Micelles: Combining Longevity, Stability, and Stimuli Sensitivity. Multifunctional Pharmaceutical Nanocarriers, 2008. 4(1559-7083): p. 263-308.
15.He, G., L.L. Ma, J. Pan, and S. Venkatraman, ABA and BAB type triblock copolymers of PEG and PLA: A comparative study of drug release properties and “stealth” particle characteristics. International journal of pharmaceutics, 2007. 334(1–2): p. 48-55.
16.Kwon, G.S., Polymeric micelles for delivery of poorly water-soluble compounds. Critical reviews in therapeutic drug carrier systems, 2003. 20(5): p. 357-403.
17.Molineux, G., Pegylation: engineering improved pharmaceuticals for enhanced therapy. Cancer treatment reviews, 2002. 28 Suppl A: p. 13-6.
18.Adams, M.L., A. Lavasanifar, and G.S. Kwon, Amphiphilic block copolymers for drug delivery. Journal of pharmaceutical sciences, 2003. 92(7): p. 1343-55.
19.Oerlemans, C., W. Bult, M. Bos, G. Storm, J.F. Nijsen, and W.E. Hennink, Polymeric micelles in anticancer therapy: targeting, imaging and triggered release. Pharm Res, 2010. 27(12): p. 2569-89.
20.Carey, M.C. and D.M. Small, The characteristics of mixed micellar solutions with particular reference to bile. The American Journal of Medicine, 1970. 49(5): p. 590-608.
21.Carey, M.C. and D.M. Small, Micelle formation by bile salts: Physical-chemical and thermodynamic considerations. Archives of internal medicine, 1972. 130(4): p. 506-527.
22.Huang, C.K., C.L. Lo, H.H. Chen, and G.H. Hsiue, Multifunctional micelles for cancer cell targeting, distribution imaging, and anticancer drug delivery. Adv Funct Mater, 2007. 17(14): p. 2291-2297.
23.Kulthe, S.S., N.N. Inamdar, Y.M. Choudhari, S.M. Shirolikar, L.C. Borde, and V.K. Mourya, Mixed micelle formation with hydrophobic and hydrophilic Pluronic block copolymers: Implications for controlled and targeted drug delivery. Colloids and Surfaces B: Biointerfaces, 2011. 88(2): p. 691-696.
24.Shozo, M., M. Noriyuki, and S. Hitoshi, Improvement of absolute bioavailability of normally poorly absorbed drugs: inducement of the intestinal absorption of streptomycin and gentamycin by lipid-bile salt mixed micelles in rat and rabbit. International journal of pharmaceutics, 1979. 2(2): p. 101-111.
25.Mrestani, Y., L. Behbood, A. Hartl, and R.H.H. Neubert, Microemulsion and mixed micelle for oral administration as new drug formulations for highly hydrophilic drugs. European Journal of Pharmaceutics and Biopharmaceutics, 2010. 74(2): p. 219-222.
26.Muller, K., Structural dimorphism of bile salt/lecithin mixed micelles. A possible regulatory mechanism for cholesterol solubility in bile? X-ray structure analysis. Biochemistry, 1981. 20(2): p. 404-14.
27.Magee, G.A., J. French, B. Gibbon, and C. Luscombe, Bile salt/lecithin mixed micelles optimized for the solubilization of a poorly soluble steroid molecule using statistical experimental design. Drug Dev Ind Pharm, 2003. 29(4): p. 441-450.
28.Scott-Moncrieff, J.C., Z. Shao, and A.K. Mitra, Enhancement of intestinal insulin absorption by bile salt-fatty acid mixed micelles in dogs. Journal of pharmaceutical sciences, 1994. 83(10): p. 1465-9.
29.Pithavala, Y.K., J.L. Odishaw, S. Han, T.S. Wiedmann, and C.L. Zimmerman, Retinoid absorption from simple and mixed micelles in the rat intestine. Journal of pharmaceutical sciences, 1995. 84(11): p. 1360-5.
30.Brajtburg, J., S. Elberg, S.J. Travis, and G.S. Kobayashi, Treatment of Murine Candidiasis and Cryptococcosis with Amphotericin-B Incorporated into Egg Lecithin Bile-Salt Mixed Micelles. Antimicrob Agents Ch, 1994. 38(2): p. 294-299.
31.Alkan-Onyuksel, H., S. Ramakrishnan, H.B. Chai, and J.M. Pezzuto, A mixed micellar formulation suitable for the parenteral administration of taxol. Pharm Res, 1994. 11(2): p. 206-12.
32.Hammad, M.A. and B.W. Muller, Increasing drug solubility by means of bile salt-phosphatidylcholine-based mixed micelles. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 1998. 46(3): p. 361-7.
33.Hammad, M.A. and B.W. Muller, Solubility and stability of tetrazepam in mixed micelles. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 1998. 7(1): p. 49-55.
34.Hammad, M.A. and B.W. Muller, Solubility and stability of lorazepam in bile salt/soya phosphatidylcholine-mixed micelles. Drug Dev Ind Pharm, 1999. 25(4): p. 409-17.
35.Rupp, C., H. Steckel, and B.W. Muller, Solubilization of poorly water-soluble drugs by mixed micelles based on hydrogenated phosphatidylcholine. International journal of pharmaceutics, 2010. 395(1-2): p. 272-80.
36.Shankland, W., The equilibrium and structure of lecithin-cholate mixed micelles. Chemistry and physics of lipids, 1970. 4(2): p. 109-30.
37.Lichtenberg, D., R.J. Robson, and E.A. Dennis, Solubilization of phospholipids by detergents. Structural and kinetic aspects. Biochimica et biophysica acta, 1983. 737(2): p. 285-304.
38.Krishnadas, A., I. Rubinstein, and H. Onyuksel, Sterically stabilized phospholipid mixed micelles: in vitro evaluation as a novel carrier for water-insoluble drugs. Pharm Res, 2003. 20(2): p. 297-302.
39.Chiappetta, D.A. and A. Sosnik, Poly(ethylene oxide)-poly(propylene oxide) block copolymer micelles as drug delivery agents: Improved hydrosolubility, stability and bioavailability of drugs. European Journal of Pharmaceutics and Biopharmaceutics, 2007. 66(3): p. 303-317.
40.Mu, L., V.P. Elbayoumi Ta Fau - Torchilin, and V.P. Torchilin, Mixed micelles made of poly(ethylene glycol)-phosphatidylethanolamine conjugate and d-alpha-tocopheryl polyethylene glycol 1000 succinate as pharmaceutical nanocarriers for camptothecin. (0378-5173 (Print)).
41.Vakil, R. and G.S. Kwon, Poly(ethylene glycol)-b-poly(ε-caprolactone) and PEG-phospholipid form stable mixed micelles in aqueous media. Langmuir, 2006. 22(23): p. 9723-9729.
42.Danson, S., D. Ferry, V. Alakhov, J. Margison, D. Kerr, D. Jowle, M. Brampton, G. Halbert, and M. Ranson, Phase I dose escalation and pharmacokinetic study of pluronic polymer-bound doxorubicin (SP1049C) in patients with advanced cancer. British journal of cancer, 2004. 90(11): p. 2085-91.
43.Wei, Z., Research on the sports development model of small towns in Hunan region. Forum, 2009. 12: p. 176-177.
44.Gao, Y. and Z. Deng. Self-tuning measurement fusion Kalman filter with correlated measurement noises and its convergence. 2008.
45.Wei, Z., S. Yuan, Y. Chen, S. Yu, J. Hao, J. Luo, X. Sha, and X. Fang, Eur. J. Pharm. Biopharm., 2010. 75: p. 341-353.
46.Oh, K.T., T.K. Bronich, and A.V. Kabanov, Micellar formulations for drug delivery based on mixtures of hydrophobic and hydrophilic Pluronic® block copolymers. Journal of Controlled Release, 2004. 94(2-3): p. 411-422.
47.Gaucher, G., M.H. Dufresne, V.P. Sant, N. Kang, D. Maysinger, and J.C. Leroux, Block copolymer micelles: preparation, characterization and application in drug delivery. Journal of Controlled Release, 2005. 109(1-3): p. 169-188.
48.Tyrrell, Z.L., Y. Shen, and M. Radosz, Fabrication of micellar nanoparticles for drug delivery through the self-assembly of block copolymers. Progress in Polymer Science, 2010. 35(9): p. 1128-1143.
49.P. Vangeyte, S.G., R. Jérôme, About the methods of preparation of poly(ethyleneoxide)-b-poly(ε-caprolactone) nanoparticles in water Analysis by dynamic light scattering. Colloids and surfaces A: physicochemical and engineering aspects, 2004. 242(1-3): p. 203-211.
50.Koval, M., K. Preiter, C. Adles, P.D. Stahl, and T.H. Steinberg, Size of IgG-opsonized particles determines macrophage response during internalization. Experimental cell research, 1998. 242(1): p. 265-73.
51.Harashima, H., K. Sakata, K. Funato, and H. Kiwada, Enhanced Hepatic-Uptake of Liposomes through Complement Activation Depending on the Size of Liposomes. Pharmaceut Res, 1994. 11(3): p. 402-406.
52.Moghimi, S.M., A.C. Hunter, and J.C. Murray, Long-circulating and target-specific nanoparticles: Theory to practice. Pharmacological reviews, 2001. 53(2): p. 283-318.
53.Rejman, J., V. Oberle, I.S. Zuhorn, and D. Hoekstra, Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. The Biochemical journal, 2004. 377(Pt 1): p. 159-69.
54.Koo, O.M., I. Rubinstein, and H. Onyuksel, Role of nanotechnology in targeted drug delivery and imaging: a concise review. Nanomedicine-Uk, 2005. 1(3): p. 193-212.
55.Soo Choi, H., W. Liu, P. Misra, E. Tanaka, J.P. Zimmer, B. Itty Ipe, M.G. Bawendi, and J.V. Frangioni, Renal clearance of quantum dots. Nat Biotech, 2007. 25(10): p. 1165-1170.
56.Ebrahim Attia, A.B., Z.Y. Ong, J.L. Hedrick, P.P. Lee, P.L.R. Ee, P.T. Hammond, and Y.-Y. Yang, Mixed micelles self-assembled from block copolymers for drug delivery. Current Opinion in Colloid & Interface Science, 2011. 16(3): p. 182-194.
57.Kedar, U., P. Phutane, S. Shidhaye, and V. Kadam, Advances in polymeric micelles for drug delivery and tumor targeting. Nanomedicine-Uk, 2010. 6(6): p. 714-29.
58.Mansur, H.S., Quantum dots and nanocomposites. Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology, 2010. 2(2): p. 113-29.
59.Das, S., J. Dey, T. Mukhim, and K. Ismail, Effect of sodium salicylate, sodium oxalate, and sodium chloride on the micellization and adsorption of sodium deoxycholate in aqueous solutions. Journal of colloid and interface science, 2011. 357(2): p. 434-9.
60.Sigma-Aldrich, I., Sodium deoxycholate product imformation.
61.Matsuoka, K. and Y. Moroi, Micelle formation of sodium deoxycholate and sodium ursodeoxycholate (part 1). Biochimica et biophysica acta, 2002. 1580(2-3): p. 189-99.
62.Maestre, A., P. Guardado, and M.L. Moyá, Thermodynamic Study of Bile Salts Micellization. Journal of Chemical & Engineering Data, 2014. 59(2): p. 433-438.
63.Hao, L., R. Lu, D. Leaist, and P. Poulin, Aggregation number of aqueous sodium cholate micelles from mutual diffusion measurements. Journal of Solution Chemistry, 1997. 26(2): p. 113-125.
64.Natalini, B., R. Sardella, A. Gioiello, F. Ianni, A. Di Michele, and M. Marinozzi, Determination of bile salt critical micellization concentration on the road to drug discovery. Journal of pharmaceutical and biomedical analysis, 2014. 87: p. 62-81.
65.Monte, M.J., J.J. Marin, A. Antelo, and J. Vazquez-Tato, Bile acids: chemistry, physiology, and pathophysiology. World journal of gastroenterology : WJG, 2009. 15(7): p. 804-16.
66.Carey, M.C. and D.M. Small, Micelle formation by bile salts. Physical-chemical and thermodynamic considerations. Archives of internal medicine, 1972. 130(4): p. 506-27.
67.Nick Carter, M.P., Luis Albert Arias, Dynamics of Apolar Guest Solubilized in Bile Salt Micelles: Photochemistry of Acenaphthylene as a Probe to Understand the Supramolecular Characteristics of the Aggregates. American Journal of Chemistry, 2012. 2(3): p. 131-136.
68.Almeida, H., M.H. Amaral, P. Lobao, and J.M. Sousa Lobo, Applications of poloxamers in ophthalmic pharmaceutical formulations: an overview. Expert opinion on drug delivery, 2013. 10(9): p. 1223-37.
69.Pitto-Barry, A. and N.P.E. Barry, Pluronic[registered sign] block-copolymers in medicine: from chemical and biological versatility to rationalisation and clinical advances. Polymer Chemistry, 2014. 5(10): p. 3291-3297.
70.Batrakova, E.V. and A.V. Kabanov, Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers. Journal of controlled release : official journal of the Controlled Release Society, 2008. 130(2): p. 98-106.
71.Batrakova, E.V., S. Li, V.Y. Alakhov, D.W. Miller, and A.V. Kabanov, Optimal structure requirements for pluronic block copolymers in modifying P-glycoprotein drug efflux transporter activity in bovine brain microvessel endothelial cells. The Journal of pharmacology and experimental therapeutics, 2003. 304(2): p. 845-54.
72.Chong, J.Y.T., X. Mulet, L.J. Waddington, B.J. Boyd, and C.J. Drummond, Steric stabilisation of self-assembled cubic lyotropic liquid crystalline nanoparticles: high throughput evaluation of triblock polyethylene oxide-polypropylene oxide-polyethylene oxide copolymers. Soft Matter, 2011. 7(10): p. 4768-4777.
73.Gelderblom, H., J. Verweij, K. Nooter, and A. Sparreboom, Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. European Journal of Cancer, 2001. 37(13): p. 1590-8.
74.Chia-yu, s., In vitro evaluation of anti-cancer for amphotericin B with pretreatment of ethanolic extract of Taiwanofungus camphoratus and prepartion and oral pharmacokinetic study of its micellar dosage form. Mater Thesis, 2013.
75.Sparreboom, A., W.J. Loos, J. Verweij, A.I. de Vos, M.E. van der Burg, G. Stoter, and K. Nooter, Quantitation of Cremophor EL in human plasma samples using a colorimetric dye-binding microassay. Analytical biochemistry, 1998. 255(2): p. 171-5.
76.Zhang, Z., S. Tan, and S.S. Feng, Vitamin E TPGS as a molecular biomaterial for drug delivery. Biomaterials, 2012. 33(19): p. 4889-906.
77.Company, E.C., Eastman Vitamin E TPGS NF Applications and Properties. 2005.
78.Guo, Y., J. Luo, S. Tan, B.O. Otieno, and Z. Zhang, The applications of Vitamin E TPGS in drug delivery. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2013. 49(2): p. 175-86.
79.Tan, Q., W. Liu, C. Guo, and G. Zhai, Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery. International journal of nanomedicine, 2011. 6: p. 1621-30.
80.Sandor, M., A. Riechel, I. Kaplan, and E. Mathiowitz, Effect of lecithin and MgCO3 as additives on the enzymatic activity of carbonic anhydrase encapsulated in poly(lactide-co-glycolide) (PLGA) microspheres. Biochimica Et Biophysica Acta-General Subjects, 2002. 1570(1): p. 63-74.
81.Shi, X.T., Y.J. Wang, L. Ren, W. Huang, and D.A. Wang, A protein/antibiotic releasing poly(lactic-co-glycolic acid)/lecithin scaffold for bone repair applications. International journal of pharmaceutics, 2009. 373(1-2): p. 85-92.
82.Park, S.I., J.H. Kim, J.H. Lim, and C.O. Kim, Surface-modified magnetic nanoparticles with lecithin for applications in biomedicine. Current Applied Physics, 2008. 8(6): p. 706-709.
83.Ling, G., P. Zhang, W. Zhang, J. Sun, X. Meng, Y. Qin, Y. Deng, and Z. He, Development of novel self-assembled DS-PLGA hybrid nanoparticles for improving oral bioavailability of vincristine sulfate by P-gp inhibition. Journal of controlled release : official journal of the Controlled Release Society, 2010. 148(2): p. 241-8.
84.Zhu, N., F.Z. Cui, K. Hu, and L. Zhu, Biomedical modification of poly(L-lactide) by blending with lecithin. Journal of Biomedical Materials Research Part A, 2007. 82A(2): p. 455-461.
85.CHUMNANPUEN, P., Systems Biology of Yeast Lipid Metabolism. 2012.
86.Kimura, I., Medical benefits of using natural compounds and their derivatives having multiple pharmacological actions. Yakugaku Zasshi, 2006. 126(3): p. 133-143.
87.Gupta, S.C., J.H. Kim, S. Prasad, and B.B. Aggarwal, Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer and Metastasis Reviews, 2010. 29(3): p. 405-434.
88.Pan, M.H., C.S. Lai, S. Dushenkov, and C.T. Ho, Modulation of inflammatory genes by natural dietary bioactive compounds. Journal of agricultural and food chemistry, 2009. 57(11): p. 4467-4477.
89.Harvey, A.L., R.L. Clark, S.P. Mackay, and B.F. Johnston, Current strategies for drug discovery through natural products. Expert Opinion on Drug Discovery, 2010. 5(6): p. 559-568.
90.Arakawa, R., M. Yamaguchi, H. Hotta, T. Osakai, and T. Kimoto, Product analysis of caffeic acid oxidation by on-line electrochemistry/ electrospray ionization mass spectrometry. Journal of the American Society for Mass Spectrometry, 2004. 15(8): p. 1228-1236.
91.Coimbra, M., B. Isacchi, L. van Bloois, J.S. Torano, A. Ket, X.J. Wu, F. Broere, J.M. Metselaar, C.J.F. Rijcken, G. Storm, R. Bilia, and R.M. Schiffelers, Improving solubility and chemical stability of natural compounds for medicinal use by incorporation into liposomes. International journal of pharmaceutics, 2011. 416(2): p. 433-442.
92.Wang, S., R. Su, S. Nie, M. Sun, J. Zhang, D. Wu, and N. Moustaid-Moussa, Application of nanotechnology in improving bioavailability and bioactivity of diet-derived phytochemicals. The Journal of nutritional biochemistry, 2013.
93.Prasad, S., A.K. Tyagi, and B.B. Aggarwal, Recent Developments in Delivery, Bioavailability, Absorption and Metabolism of Curcumin: the Golden Pigment from Golden Spice. Cancer research and treatment : official journal of Korean Cancer Association, 2014. 46(1): p. 2-18.
94.Dulbecco, P. and V. Savarino, Therapeutic potential of curcumin in digestive diseases. World journal of gastroenterology : WJG, 2013. 19(48): p. 9256-70.
95.Sandur, S.K., M.K. Pandey, B. Sung, K.S. Ahn, A. Murakami, G. Sethi, P. Limtrakul, V. Badmaev, and B.B. Aggarwal, Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis, 2007. 28(8): p. 1765-73.
96.Mohanty, C., M. Das, and S.K. Sahoo, Emerging role of nanocarriers to increase the solubility and bioavailability of curcumin. Expert opinion on drug delivery, 2012. 9(11): p. 1347-64.
97.Bansal, S.S., M. Goel, F. Aqil, M.V. Vadhanam, and R.C. Gupta, Advanced drug delivery systems of curcumin for cancer chemoprevention. Cancer prevention research, 2011. 4(8): p. 1158-71.
98.Metzler, M., E. Pfeiffer, S.I. Schulz, and J.S. Dempe, Curcumin uptake and metabolism. BioFactors, 2013. 39(1): p. 14-20.
99.Anand, P., S.G. Thomas, A.B. Kunnumakkara, C. Sundaram, K.B. Harikumar, B. Sung, S.T. Tharakan, K. Misra, I.K. Priyadarsini, K.N. Rajasekharan, and B.B. Aggarwal, Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochemical pharmacology, 2008. 76(11): p. 1590-611.
100.Bar-Sela, G., R. Epelbaum, and M. Schaffer, Curcumin as an Anti-Cancer Agent: Review of the Gap Between Basic and Clinical Applications. Current Medicinal Chemistry, 2010. 17(3): p. 190-197.
101.Maheshwari, R.K., A.K. Singh, J. Gaddipati, and R.C. Srimal, Multiple biological activities of curcumin: a short review. Life sciences, 2006. 78(18): p. 2081-7.
102.Jurenka, J.S., Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Alternative medicine review : a journal of clinical therapeutic, 2009. 14(2): p. 141-53.
103.Naksuriya, O., S. Okonogi, R.M. Schiffelers, and W.E. Hennink, Curcumin nanoformulations: A review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment. Biomaterials, 2014.
104.Priyadarsini, K.I., Photophysics, photochemistry and photobiology of curcumin: Studies from organic solutions, bio-mimetics and living cells. Journal of Photochemistry and Photobiology C-Photochemistry Reviews, 2009. 10(2): p. 81-95.
105.Yallapu, M.M., M. Jaggi, and S.C. Chauhan, Curcumin nanomedicine: a road to cancer therapeutics. Current pharmaceutical design, 2013. 19(11): p. 1994-2010.
106.Aggarwal, B.B. and K.B. Harikumar, Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. The international journal of biochemistry & cell biology, 2009. 41(1): p. 40-59.
107.Anand, P., A.B. Kunnumakkara, R.A. Newman, and B.B. Aggarwal, Bioavailability of curcumin: problems and promises. Molecular pharmaceutics, 2007. 4(6): p. 807-18.
108.Aggarwal, B.B. and B. Sung, Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends in pharmacological sciences, 2009. 30(2): p. 85-94.
109.Esatbeyoglu, T., P. Huebbe, I.M. Ernst, D. Chin, A.E. Wagner, and G. Rimbach, Curcumin--from molecule to biological function. Angewandte Chemie, 2012. 51(22): p. 5308-32.
110.Kurita, T. and Y. Makino, Novel curcumin oral delivery systems. Anticancer research, 2013. 33(7): p. 2807-21.
111.Souza, C.R.A., S.F. Osme, and M.B.A. Gloria, Stability of curcuminoid pigments in model systems. Journal of Food Processing and Preservation, 1997. 21(5): p. 353-363.
112.Stankovic, I., CURCUMIN Chemical and Technical Assessment (CTA). 2004.
113.Yang, K.Y., L.C. Lin, T.Y. Tseng, S.C. Wang, and T.H. Tsai, Oral bioavailability of curcumin in rat and the herbal analysis from Curcuma longa by LC-MS/MS. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2007. 853(1-2): p. 183-9.
114.Wahlstrom, B. and G. Blennow, A study on the fate of curcumin in the rat. Acta Pharmacol Toxicol (Copenh), 1978. 43(2): p. 86-92.
115.Pan, M.-H., T.-M. Huang, and J.-K. Lin, Biotransformation of Curcumin Through Reduction and Glucuronidation in Mice. Drug Metabolism and Disposition, 1999. 27(4): p. 486-494.
116.Vareed, S.K., M. Kakarala, M.T. Ruffin, J.A. Crowell, D.P. Normolle, Z. Djuric, and D.E. Brenner, Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008. 17(6): p. 1411-7.
117.Ireson, C.R., D.J. Jones, S. Orr, M.W. Coughtrie, D.J. Boocock, M.L. Williams, P.B. Farmer, W.P. Steward, and A.J. Gescher, Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2002. 11(1): p. 105-11.
118.Garcea, G., D.P. Berry, D.J. Jones, R. Singh, A.R. Dennison, P.B. Farmer, R.A. Sharma, W.P. Steward, and A.J. Gescher, Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2005. 14(1): p. 120-5.
119.Sharma, R.A., A.J. Gescher, and W.P. Steward, Curcumin: The story so far. European Journal of Cancer, 2005. 41(13): p. 1955-1968.
120.Arora, S., S. Singh, G.A. Piazza, C.M. Contreras, J. Panyam, and A.P. Singh, Honokiol: a novel natural agent for cancer prevention and therapy. Current molecular medicine, 2012. 12(10): p. 1244-52.
121.Tsai, T.H., C.J. Chou, F.C. Cheng, and C.F. Chen, Pharmacokinetics of Honokiol after Intravenous Administration in Rats Assessed Using High-Performance Liquid-Chromatography. Journal of Chromatography B-Biomedical Applications, 1994. 655(1): p. 41-45.
122.Tsai, T.H., C.F. Chou Cj Fau - Chen, and C.F. Chen, Disposition of magnolol after intravenous bolus and infusion in rabbits. (0090-9556 (Print)).
123.Tsai, T.H., C.J. Chou, T.F. Lee, L.C.H. Wang, and C.F. Chen, Pharmacokinetic and Pharmacodynamic Studies of Magnolol after Oral Administration in Rats. Pharmacy and Pharmacology Communications, 1996. 2(4): p. 191-193.
124.Lin, S.P., S.Y. Tsai, P.D. Lee Chao, Y.C. Chen, and Y.C. Hou, Pharmacokinetics, bioavailability, and tissue distribution of magnolol following single and repeated dosing of magnolol to rats. Planta medica, 2011. 77(16): p. 1800-5.
125.Wu, X., X. Chen, and Z. Hu, High-performance liquid chromatographic method for simultaneous determination of honokiol and magnolol in rat plasma. Talanta, 2003. 59(1): p. 115-21.
126.Bohmdorfer, M., A. Maier-Salamon, B. Taferner, G. Reznicek, T. Thalhammer, S. Hering, A. Hufner, W. Schuhly, and W. Jager, In vitro metabolism and disposition of honokiol in rat and human livers. Journal of pharmaceutical sciences, 2011. 100(8): p. 3506-16.
127.Hattori M Fau - Sakamoto, T., Y. Sakamoto T Fau - Endo, N. Endo Y Fau - Kakiuchi, K. Kakiuchi N Fau - Kobashi, T. Kobashi K Fau - Mizuno, T. Mizuno T Fau - Namba, and T. Namba, Metabolism of magnolol from magnoliae cortex. I. Application of liquid chromatography-mass spectrometry to the analysis of metabolites of magnolol in rats. (0009-2363 (Print)).
128.Hattori M Fau - Endo, Y., S. Endo Y Fau - Takebe, K. Takebe S Fau - Kobashi, N. Kobashi K Fau - Fukasaku, T. Fukasaku N Fau - Namba, and T. Namba, Metabolism of magnolol from Magnoliae cortex. II. Absorption, metabolism and excretion of [ring-14C]magnolol in rats. (0009-2363 (Print)).
129.Tsai, T.H., C.F. Chou Cj Fau - Chen, and C.F. Chen, Glucuronidation of magnolol assessed using HPLC/fluorescence. (0032-0943 (Print)).
130.Tsai, T.H., C.F. Chou Cj Fau - Chen, and C.F. Chen, Pharmacokinetics and brain distribution of magnolol in the rat after intravenous bolus injection. (0022-3573 (Print)).
131.Wang, X., X. Duan, G. Yang, X. Zhang, L. Deng, H. Zheng, C. Deng, J. Wen, N. Wang, C. Peng, X. Zhao, Y. Wei, and L. Chen, Honokiol crosses BBB and BCSFB, and inhibits brain tumor growth in rat 9L intracerebral gliosarcoma model and human U251 xenograft glioma model. PloS one, 2011. 6(4): p. e18490.
132.Wang, X.H., L.L. Cai, X.Y. Zhang, L.Y. Deng, H. Zheng, C.Y. Deng, J.L. Wen, X. Zhao, Y.Q. Wei, and L.J. Chen, Improved solubility and pharmacokinetics of PEGylated liposomal honokiol and human plasma protein binding ability of honokiol. International journal of pharmaceutics, 2011. 410(1-2): p. 169-74.
133.Goswami, S.K. and D.K. Das, Resveratrol and chemoprevention. Cancer letters, 2009. 284(1): p. 1-6.
134.Fremont, L., Biological effects of resveratrol. Life sciences, 2000. 66(8): p. 663-73.
135.Soleas, G.J., E.P. Diamandis, and D.M. Goldberg, Resveratrol: A molecule whose time has come? And gone? Clinical biochemistry, 1997. 30(2): p. 91-113.
136.Neves, A.R., M. Lucio, S. Martins, J.L. Lima, and S. Reis, Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability. International journal of nanomedicine, 2013. 8: p. 177-87.
137.Tome-Carneiro, J., M. Larrosa, A. Gonzalez-Sarrias, F.A. Tomas-Barberan, M.T. Garcia-Conesa, and J.C. Espin, Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence. Current pharmaceutical design, 2013. 19(34): p. 6064-93.
138.Neves, A.R., M. Lucio, J.L. Lima, and S. Reis, Resveratrol in medicinal chemistry: a critical review of its pharmacokinetics, drug-delivery, and membrane interactions. Current Medicinal Chemistry, 2012. 19(11): p. 1663-81.
139.Ramassamy, C., Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. European journal of pharmacology, 2006. 545(1): p. 51-64.
140.Stervbo, U., O. Vang, and C. Bonnesen, A review of the content of the putative chemopreventive phytoalexin resveratrol in red wine. Food chemistry, 2007. 101(2): p. 449-457.
141.Bertelli, A.A.E., L. Giovannini, R. DeCaterina, W. Bernini, M. Migliori, M. Fregoni, L. Bavaresco, and A. Bertelli, Antiplatelet activity of cis-resveratrol. Drugs under Experimental and Clinical Research, 1996. 22(2): p. 61-63.
142.Vian, M.A., V. Tomao, S. Gallet, P.O. Coulomb, and J.M. Lacombe, Simple and rapid method for cis- and trans-resveratrol and piceid isomers determination in wine by high-performance liquid chromatography using Chromolith columns. Journal of Chromatography A, 2005. 1085(2): p. 224-229.
143.Amri, A., J.C. Chaumeil, S. Sfar, and C. Charrueau, Administration of resveratrol: What formulation solutions to bioavailability limitations? Journal of Controlled Release, 2012. 158(2): p. 182-193.
144.Trela, B.C. and A.L. Waterhouse, Resveratrol: Isomeric molar absorptivities and stability. Journal of agricultural and food chemistry, 1996. 44(5): p. 1253-1257.
145.Walle, T., F. Hsieh, M.H. DeLegge, J.E. Oatis, and U.K. Walle, High absorption but very low bioavailability of oral resveratrol in humans. Drug Metabolism and Disposition, 2004. 32(12): p. 1377-1382.
146.Goldberg, D.M., J. Yan, and G.J. Soleas, Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clinical biochemistry, 2003. 36(1): p. 79-87.
147.Vitaglione, P., S. Sforza, G. Galaverna, C. Ghidini, N. Caporaso, P.P. Vescovi, V. Fogliano, and R. Marchelli, Bioavailability of trans-resveratrol from red wine in humans. Molecular nutrition & food research, 2005. 49(5): p. 495-504.
148.Wenzel, E. and V. Somoza, Metabolism and bioavailability of trans-resveratrol. Molecular nutrition & food research, 2005. 49(5): p. 472-81.
149.Liang, L., X. Liu, Q. Wang, S. Cheng, S. Zhang, and M. Zhang, Pharmacokinetics, tissue distribution and excretion study of resveratrol and its prodrug 3,5,4′-tri-O-acetylresveratrol in rats. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2013. 20(6): p. 558-563.
150.Bertelli, A., A.A. Bertelli, A. Gozzini, and L. Giovannini, Plasma and tissue resveratrol concentrations and pharmacological activity. Drugs Exp Clin Res, 1998. 24(3): p. 133-8.
151.Vitrac, X., A. Desmouliere, B. Brouillaud, S. Krisa, G. Deffieux, N. Barthe, J. Rosenbaum, and J.M. Merillon, Distribution of [14C]-trans-resveratrol, a cancer chemopreventive polyphenol, in mouse tissues after oral administration. Life sciences, 2003. 72(20): p. 2219-33.
152.Lancon, A., D. Delmas, H. Osman, J.P. Thenot, B. Jannin, and N. Latruffe, Human hepatic cell uptake of resveratrol: involvement of both passive diffusion and carrier-mediated process. Biochem Bioph Res Co, 2004. 316(4): p. 1132-1137.
153.Glatz, J.F.C. and G.J. vanderVusse, Cellular fatty acid-binding proteins: Their function and physiological significance. Progress in Lipid Research, 1996. 35(3): p. 243-282.
154.Williams, L.D., G.A. Burdock, J.A. Edwards, M. Beck, and J. Bausch, Safety studies conducted on high-purity trans-resveratrol in experimental animals. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2009. 47(9): p. 2170-82.
155.Schmitt, E., L. Lehmann, M. Metzler, and H. Stopper, Hormonal and genotoxic activity of resveratrol. Toxicology letters, 2002. 136(2): p. 133-42.
156.Jang, M., L. Cai, G.O. Udeani, K.V. Slowing, C.F. Thomas, C.W. Beecher, H.H. Fong, N.R. Farnsworth, A.D. Kinghorn, R.G. Mehta, R.C. Moon, and J.M. Pezzuto, Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science, 1997. 275(5297): p. 218-20.
157.Wang, Q., J. Xu, G.E. Rottinghaus, A. Simonyi, D. Lubahn, G.Y. Sun, and A.Y. Sun, Resveratrol protects against global cerebral ischemic injury in gerbils. Brain research, 2002. 958(2): p. 439-47.
158.Song, Z., R. Feng, M. Sun, C. Guo, Y. Gao, L. Li, and G. Zhai, Curcumin-loaded PLGA-PEG-PLGA triblock copolymeric micelles: Preparation, pharmacokinetics and distribution in vivo. Journal of colloid and interface science, 2011. 354(1): p. 116-23.
159.Gong, C., S. Deng, Q. Wu, M. Xiang, X. Wei, L. Li, X. Gao, B. Wang, L. Sun, Y. Chen, Y. Li, L. Liu, Z. Qian, and Y. Wei, Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable polymeric micelles. Biomaterials, 2013. 34(4): p. 1413-32.
160.Duan, J., Y. Zhang, S. Han, Y. Chen, B. Li, M. Liao, W. Chen, X. Deng, J. Zhao, and B. Huang, Synthesis and in vitro/in vivo anti-cancer evaluation of curcumin-loaded chitosan/poly(butyl cyanoacrylate) nanoparticles. International journal of pharmaceutics, 2010. 400(1-2): p. 211-20.
161.Kim, T.H., H.H. Jiang, Y.S. Youn, C.W. Park, K.K. Tak, S. Lee, H. Kim, S. Jon, X. Chen, and K.C. Lee, Preparation and characterization of water-soluble albumin-bound curcumin nanoparticles with improved antitumor activity. International journal of pharmaceutics, 2011. 403(1-2): p. 285-91.
162.Sun, J., C. Bi, H.M. Chan, S. Sun, Q. Zhang, and Y. Zheng, Curcumin-loaded solid lipid nanoparticles have prolonged in vitro antitumour activity, cellular uptake and improved in vivo bioavailability. Colloids and surfaces. B, Biointerfaces, 2013. 111C: p. 367-375.
163.Takahashi, M., S. Uechi, K. Takara, Y. Asikin, and K. Wada, Evaluation of an oral carrier system in rats: bioavailability and antioxidant properties of liposome-encapsulated curcumin. Journal of agricultural and food chemistry, 2009. 57(19): p. 9141-6.
164.Khalil, N.M., T.C. do Nascimento, D.M. Casa, L.F. Dalmolin, A.C. de Mattos, I. Hoss, M.A. Romano, and R.M. Mainardes, Pharmacokinetics of curcumin-loaded PLGA and PLGA-PEG blend nanoparticles after oral administration in rats. Colloids and surfaces. B, Biointerfaces, 2013. 101: p. 353-60.
165.Qiu, N., L.L. Cai, D. Xie, G. Wang, W. Wu, Y. Zhang, H. Song, H. Yin, and L. Chen, Synthesis, structural and in vitro studies of well-dispersed monomethoxy-poly(ethylene glycol)-honokiol conjugate micelles. Biomedical materials, 2010. 5(6): p. 065006.
166.Gong, C., X. Wei, X. Wang, Y. Wang, G. Guo, Y. Mao, F. Luo, and Z. Qian, Biodegradable self-assembled PEG-PCL-PEG micelles for hydrophobic honokiol delivery: I. Preparation and characterization. Nanotechnology, 2010. 21(21): p. 215103.
167.Zheng, X., X. Wang, M. Gou, J. Zhang, K. Men, L. Chen, F. Luo, X. Zhao, Y. Wei, and Z. Qian, A novel transdermal honokiol formulation based on Pluronic F127 copolymer. Drug delivery, 2010. 17(3): p. 138-44.
168.Zheng, X., B. Kan, M. Gou, S. Fu, J. Zhang, K. Men, L. Chen, F. Luo, Y. Zhao, X. Zhao, Y. Wei, and Z. Qian, Preparation of MPEG-PLA nanoparticle for honokiol delivery in vitro. International journal of pharmaceutics, 2010. 386(1-2): p. 262-7.
169.Singh, G. and R.S. Pai, In-vitro/in-vivo characterization of trans-resveratrol-loaded nanoparticulate drug delivery system for oral administration. The Journal of pharmacy and pharmacology, 2014.
170.Lu, X., C. Ji, H. Xu, X. Li, H. Ding, M. Ye, Z. Zhu, D. Ding, X. Jiang, X. Ding, and X. Guo, Resveratrol-loaded polymeric micelles protect cells from Aβ-induced oxidative stress. International journal of pharmaceutics, 2009. 375(1-2): p. 89-96.
171.Alexandridis, P. and T.A. Hatton, Poly(Ethylene Oxide)-Poly(Propylene Oxide)-Poly(Ethylene Oxide) Block-Copolymer Surfactants in Aqueous-Solutions and at Interfaces - Thermodynamics, Structure, Dynamics, and Modeling. Colloid Surface A, 1995. 96(1-2): p. 1-46.
172.Abdelbary, G.A. and M.I. Tadros, Brain targeting of olanzapine via intranasal delivery of core-shell difunctional block copolymer mixed nanomicellar carriers: in vitro characterization, ex vivo estimation of nasal toxicity and in vivo biodistribution studies. International journal of pharmaceutics, 2013. 452(1-2): p. 300-10.
173.Pepic, I., J. Lovric, A. Hafner, and J. Filipovic-Grcic, Powder form and stability of Pluronic mixed micelle dispersions for drug delivery applications. Drug Dev Ind Pharm, 2014. 40(7): p. 944-51.
174.Zhao, Y., Y. Li, J. Ge, N. Li, and L.B. Li, Pluronic-poly (acrylic acid)-cysteine/Pluronic L121 mixed micelles improve the oral bioavailability of paclitaxel. Drug Dev Ind Pharm, 2013.
175.Lee, E.S., Y.T. Oh, Y.S. Youn, M. Nam, B. Park, J. Yun, J.H. Kim, H.T. Song, and K.T. Oh, Binary mixing of micelles using Pluronics for a nano-sized drug delivery system. Colloid Surface B, 2011. 82(1): p. 190-195.
176.Chong-SHU, H., Development of Self-Assembling Lecithin-Based Polymeric Mixed Micellar Systems for Quercetin in Cancer Treatment. Master thesis 2013.