本研究使用聚乙二醇單甲醚和左旋-丙交酯以開環聚合合成三種不同分子量的聚乙二醇單甲醚-聚乳酸(mPEG-PLLA)雙團聯共聚物，並以凝膠層析滲透儀(GPC)分析其分子量。
利用共沉澱法將共聚物和粒徑為15-20 nm的四氧化三鐵奈米粒子於水溶液中共組裝形成微胞，使用螢光光譜儀測量臨界微胞濃度，觀察在不同奈米粒子濃度和不同疏水鏈段聚合度時，其臨界微胞濃度、微胞化自由能的變化。探討(1)在不同奈米粒子濃度下疏水鏈段聚合度和臨界微胞濃度冪次關係中的指數(a0)。(2)在不同疏水鏈段聚合度下臨界微胞濃度的自然對數和奈米粒子濃度冪次關係的指數(n0)；以動態光散射儀測量其微胞平均粒徑，觀察其微胞粒徑在不同奈米粒子濃度、不同疏水鏈段聚合度之變化。探討(1)在不同奈米粒子濃度下微胞粒徑和疏水鏈段聚合度冪次關係中的指數(a)。(2)在不同疏水鏈段聚合度下微胞粒徑和奈米粒子濃度冪次關係中的指數(n)；以熱重分析儀分析(TGA)測量微胞中奈米粒子的含量，探討奈米粒子的被包覆率對奈米粒子濃度和疏水鏈段聚合度的關係。並計算奈米粒子於水溶液和微胞核中的平衡常數和分配自由能。
實驗結果發現臨界微胞濃度隨著奈米粒子濃度增加或疏水鏈段聚合度增加而下降，微胞化自由能(負值)的絕對值隨著奈米粒子濃度增加或疏水鏈段聚合度增加而上升。其臨界微胞濃度的自然對數和奈米粒子濃度冪次關係的指數(n0)隨著疏水鏈段長度增加而下降。平均微胞粒徑隨著奈米粒子濃度增加和疏水鏈段長度增加而上升。其微胞粒徑和奈米粒子濃度冪次關係中的指數(n)隨著疏水鏈段長度上升而下降。四氧化三鐵奈米粒子之包覆率隨著奈米粒子濃度增加而下降，隨著疏水鏈段長度增加而上升。奈米粒子於水溶液和微胞核中的平衡常數(K)隨著疏水鏈段長度增加而上升，奈米粒子濃度上升而下降。分配自由能(負值)的絕對值隨著疏水鏈段長度增加而上升；隨著奈米粒子濃度增加而下降。實驗發現當四氧化三鐵奈米粒子濃度愈高時，其微胞化自由能(負值)的絕對值愈高，而奈米粒子的分配自由能(負值)的絕對值愈低，表示隨著奈米粒子濃度增加共聚物自組裝的推動力愈大，而奈米粒子自組裝的推動力卻愈小，奈米粒子濃度對於兩種自由能的影響相反。

This work is to synthesize methoxypoly(ethylene glycol)-poly(L-lactide) (mPEG-PLLA) diclock copolymers with three different lengths of hydrophobic (PLLA) segments by using ring-opening polymerization, and we used gel permeation chromatography (GPC) to determine the molecular weight of mPEG-PLLA diblock copolymer.
mPEG-PLLA diblock copolymers and iron (Ⅱ, Ⅲ) oxide nanoparticles with 15-20 nm average particle size are co-assembled in deionized water by using co-precipitation method. Then we determined the critical micelle concentration (CMC) of diblock copolymers solution by using fluorescent probe with various concentrations of iron oxide nanoparticles and various degrees of polymerization (DP) of hydrophobic (PLLA) segments. And we discussed (1) the power-law exponents (a0) for the CMC versus the DP of hydrophobic segments of diblock copolymers at different concentrations of iron oxide nanoparticles, and (2) The power-law exponents (n0) for natural logarithm of CMC versus the concentrations of iron oxide nanoparticles at different DP of hydrophobic segments.
Then we measured the average particle size of mPEG-PLLA diblock copolymer micelles in aqueous solutions by using dynamic light scattering (DLS) with various concentrations of iron oxide nanoparticles and various DP of hydrophobic segments. And we discussed (1) the power-law exponents (a) for the average particle size of micelle versus the DP of hydrophobic segments at different concentrations of iron (Ⅱ, Ⅲ) oxide nanoparticles. (2) The power-law exponents (n) for the average particle size of micelles versus the concentrations of iron oxide nanoparticles at different DP of hydrophobic segments.
Last we measured the content of iron oxide nanoparticles in diblock copolymer micelles with various concentrations of iron oxide nanoparticles and various DP of hydrophobic segments by using thermogravimetric analysis (TGA). And we calculated the encapsulation efficiency, the equilibrium constant between aqueous solutions and micelles, and the Gibbs free energy of partition at different concentrations of iron (Ⅱ, Ⅲ) oxide nanoparticles and different DP of hydrophobic segments.
Experimental results show that CMC decreases with increasing concentrations of iron oxide nanoparticles and DP of hydrophobic segments. Average particle size of diblock copolymer micelles increases as concentrations of iron oxide nanoparticles and DP of hydrophobic segments increases. And the power-law exponents (n0) for natural logarithm of CMC versus the concentrations of iron oxide nanoparticles and the power-law exponents (n) for the average particle size of micelles versus the concentrations of iron oxide nanoparticles decrease with increasing DP of hydrophobic segments. The encapsulation efficiency of iron oxide nanoparticles and the equilibrium constant increase with increasing DP of hydrophobic segment but decreases with increasing concentrations of iron oxide nanoparticles. The absolute value of Gibbs free energy of partition (negative value) increases with concentrations of iron oxide nanoparticles but decreases with increasing DP of hydrophobic segments. From the results we find when the concentrations of iron oxide nanoparticles increases the absolute value of Gibbs free energy of micellization also increases, whereas the Gibbs free energy of partition decreases. It means the concentrations of iron oxide nanoparticles has an opposite effect on copolymer assembly and iron oxide nanoparticles assembly.
 

1. G. Riess, Micellization of block copolymers. Progress in Polymer Science,28, 1107-1170 (2003)
2. K. S. Ho1 and M. S. Shoichet, Design considerations of polymeric nanoparticle micelles for chemotherapeutic delivery. Current Opinion in Chemical Engineering,2, 53–59 (2013)
3. S. Li and M. Vert, Synthesis, characterization and stereocomplex-induced gelation of block copolymers prepared by ring-opening polymerization of L (D)-lactide in the presence of poly (ethylene glycol). Macromolecules ,36, 8008-8014 (2003).
4. Y. Shibasaki, B.S. Kim,a A.J. Young,A.L. McLoon, S.C. Ekkerb and T. A Taton, Crosslinked, glassy styrenic surfactants stabilize quantum dots against environmental extremes. Journal of Materials Chemistry, 19, 6324–6327 (2009).
5. B.S. Kim, J.M Qiu, J.P Wang, and T.A Taton, Magnetomicelles:  Composite Nanostructures from Magnetic Nanoparticles and Cross-Linked Amphiphilic Block Copolymers. Nano Letters, 5 , 1987–1991(2005).
6. B.S. Kim and T.A. Taton, Joint carrier recovery and turbo decoding method for TDMA burst MODEM under very low SNRs. Langmuir, 23, 2198-2202 (2006).
7. N. Nasongkla,E. Bey, J. Ren, H. Ai, C. Khemtong,J. S. Guthi, S. F. Chin,A. D. Sherry, D. A. Boothman, and J. Gao, Multifunctional Polymeric Micelles as Cancer-Targeted, MRI-Ultrasensitive Drug Delivery Systems. Nano Letters., 6 , 2427–2430 (2006).
8. C. Sanson, O. Diou, J. Thevenot, , E. Ibarboure, A. Soum, A. Brulet, S. Miraux, E. Thiaudiere, S. Tan, A. Brisson, V. Dupuis, O. Sandre, and S. Lecommandoux, Doxorubicin Loaded Magnetic Polymersomes: Theranostic Nanocarriers for MR Imaging and Magneto-Chemotherapy. ACS Nano, 5 , 1122–1140 (2011).
9. Y. Kang, T.A. Taton,Core/Shell Gold Nanoparticles by Self‐Assembly and Crosslinking of Micellar, Block‐Copolymer Shells. Angew Chem Int Ed, 44 , 409-412 (2005)
10. H. Y. Chen, S. Abraham, J. Mendenhall, S. C. Delamarre, K. Smith, I. Kim, and C.A. Batt, Encapsulation of Single Small GoldNanoparticles by Diblock Copolymers
11. H. Cui1, Z. Chen, S. Zhong, K. L. Wooley, D. J. Pochan1, Block Copolymer Assembly via Kinetic Control. Science,317, 647-650 (2007).
12. E.R. Zubarev, J. Xu, A. Sayyad, J.D. Gibson, Amphiphilicity-Driven Organization of Nanoparticles into Discrete Assemblies. Journal of the American Chemical Society,128, 15098–15099 (2006).
13. A.Vila,A.Sanchez, C. Pérez and M. J. Alonso , PLA‐PEG Nanospheres: New Carriers for transmucosal delivery of proteins and plasmid DNA. Polymers for Advanced Technologies ,13, 851-858 (2002).
14. M. L. Adams, A.Lavasanifar and G.S. Kwon, Amphiphilic block copolymers for drug delivery. Journal of Pharmaceutical Sciences ,92, 1343-1355 (2003).
15. W. Lee, Y. Li and I. Chu, Amphiphilic poly(D,L-lactic acid)/poly(ethylene glycol)/poly(D,L-lactic acid) nanogels for controlled release of hydrophobic drugs. Macromolecular Bioscience ,6, 846-854 (2006).
16. N.Ahmed, H.Fessi and A.Elaissari, Theranostic applications of nanoparticles in cancer. Durg Discover Today,17, 928-934 (2012).
17. C.H.Cunningham, T.Arai, P.C.Yang, M.V.McConnell, J.M. Pauly and S.M. Conolly, Positive contrast magnetic resonance imaging of cells labeled with magnetic nanoparticles. Magnetic Resonance in Medicine ,53,999 –1005 (2005).
18. M. J. Rosen, Surfactants and interfacial phenomena, John Wiley & Sons, Inc. , New York, USA. Chapter 3 (2004).
19. J. L. Anderson, V. Pino, E. C. Hagberg, V. V. Sheares and D. W. Armstrong , Surfactant solvation effects and micelle formation in ionic liquids. Chemical Communications, 2444-2445 (2003).
20. T. Inoue, H. Ebina, B. Dong and L. Zheng, Electrical conductivity Study on micelle formation of long-chain imidazolium ionic liquids in aqueous solution. Journal of Colloid and Interface Science ,314, 236-241 (2007).
21. H. Schott, Solubilization of a water-insoluble dye as a method for determining micellar molecular weights. The Journal of Physical Chemistry ,70, 2966-2973 (1966).
22. X. Li, J. Ji, X. Wang, Y. Wang and J. Shen, Stability and drug loading of spontaneous vesicles of comb-like PEG derivates. Macromolecular Rapid Communications ,28, 660-665 (2007).
23. A. V. Kabanov,I. R. Nazarova , I. V. Astafieva, E. V. Batrakova, V. Y. Alakhov and A. A. Yaroslavov, Micelle formation and solubilization of fluorescent probes in poly(oxyethylene-b-oxypropylene -b-oxyethylene) solutions. Macromolecules, 28, 2303-2314 (1995).
24. C. L. Zhao, M. A. Winnik, G. Riess and M. D. Croucher, Fluorescence probe techniques used to study micelle formation in water-soluble block copolymers. Langmuir ,6, 514-516 (1990).
25. Z. Gao and A. Eisenberg, A model of micellization for block copolymers in solutions. Macromolecules ,26, 7353-7360 (1993).
26. K. Kalyanasundaram and J. Thomas, Environmental effects on vibronic band intensities in pyrene monomer fluorescence and their application in studies of micellar systems. Journal of the American Chemical Society ,99, 2039-2044 (1977).
27. L. Liu, C. Li , X. Liu and B. He, Micellar formation in aqueous milieu from biodegradable triblock copolymer polylactide/poly(ethylene glycol)/polylactide , Journal of Applied Polymer Science, 80, 1976–1982 (2001)
28. M. Wilhelm, C.L. Zhao, Y. Wang, R. Xu and M. A. Winnik , Poly(styrene-ethylene oxide) block copolymer micelle formation in water: a fluorescence probe study, Macromolecules, 24, 1033-1040 (1991).
29. Y. Hu, X. Jiang, Y. Ding, L. Zhang, C. Yang, J. Zhang, J. Chen and Y. Yang, Preparation and drug release behaviors of nimodipine-loaded poly (caprolactone)–poly (ethylene oxide)–polylactide amphiphilic copolymer nanoparticles. Biomaterials ,24, 2395-2404 (2003).
30. M. Talelli, C. Rijcken, T. Lammers, P.R. Seevinck,G. Storm, C. F. van Nostrum, and W. E. Hennink, Superparamagnetic Iron Oxide Nanoparticles Encapsulated in Biodegradable Thermosensitive Polymeric Micelles: Toward a Targeted Nanomedicine Suitable for Image-Guided Drug Delivery. Langmuir, 25, 2060-2067 (2009).
31. R. J. Hickey, A. S. Haynes, J. M. Kikkawa and S. J Park, Controlling the Self-Assembly Structure of Magnetic Nanoparticles and Amphiphilic Block-Copolymers: From Micelles to Vesicles. Journal of the American Chemical Society,133, 1517–1525 (2011).
32. H. Ai,C. Flask,B. Weinberg,X. Shuai,M. D. Pagel,D. Farrell,J. Duerk and J.Gao, Magnetite-Loaded Polymeric Micelles as Ultrasensitive Magmetic-Resonance Probes. Advances Materials,17,1949-1952 (2005).
33. J. Hu, Y. Qian, X.Wang, T. Liu, and S. Liu, Drug-Loaded and Superparamagnetic Iron Oxide Nanoparticle Surface-Embedded Amphiphilic Block Copolymer Micelles for Integrated Chemotherapeutic Drug Delivery and MR Imaging. Langmuir ,28, 2073–2082 (2012).
34. B. S. Kim, and T. A. Taton, Multicomponent Nanoparticles via Self-Assembly with Cross-Linked Block Copolymer Surfactants. Langmuir, 23, 2198–2202 (2007).
35. H. Y. Chen, S. Abraham, J. Mendenhall, S. C. Delamarre, K. Smith I. Kim, C. A. Batt, Encapsulation of Single Small Gold Nanoparticles by Diblock Copolymers. ChemPhysChem, 9, 388 – 392 (2008).
36. Y. Kang and T. A. Taton, Core/Shell Gold Nanoparticles by Self-Assembly and Crosslinking of Micellar, Block-Copolymer Shells. Angewandte Chemie,117,413-416 (2005).
37. H. D. Koh, N. G. Kang, and J. S. Lee, Location Control of Au/CdS Nanoparticles in Block Copolymer Micelles. Langmuir, 23, 11425-11429(2007).
38. 黃詩喬, 聚醚-聚乳酸雙團聯共聚物水溶液中自組裝及電解質效應,臺灣科技大學碩士論文, 第50頁(2015)。
39. G. H. Domeselaar , G. S. Kwon , L. C. Andrew ,D. S. Wishart, Application of solid phase peptide synthesis to engineering PEO-peptide block copolymers for drug delivery. Colloids and Surfaces B: Biointerfaces 30, 323-334 (2003).
40. D. C. Dong and M. A. Winnik, The Py scale of solvent polarities. Canadian Journal of Chemistry 62, 2560-5 (1984).
41. D. Ling and T. Hyeon, Chemical Design of Biocompatible Iron Oxide
Nanoparticles for Medical Applications.Small,9,1450-1466 (2013).
42. S.C. Owen , P.Y. Chana, M.S. Shoicheta, Polymeric micelle stability. , Nano Today 7, 53—65 (2012).
43. Z. Dai, L. Piao, X. Zhang, M. Deng, X. Chen and X. Jing, Probing the micellization of diblock and triblock copolymers of poly(l-lactide) and poly(ethylene glycol) in aqueous and NaCl salt solutions. Colloid and Polymer Science 282, 343-50 (2004).
44. T. R. Carale, Q. T. Pham and D. Blankschtein, Salt effects on intramicellar interactions and micellization of nonionic surfactants in aqueous solutions. Langmuir 10, 109-21 (1994).
45. 蔡欽宇, 聚醚-聚乳酸雙團聯共聚物在水溶液中微胞化熱力學與微胞尺寸之電解質效應,台灣科技大學碩士論文,第19頁 (2017)。
46. P. C. Hiemenz and T. P. Lodge, Polymer chemistry, second edition, CRC Press, Chapter 7 and 9 (2007).
47. Z. Zhou and B. Chu, Anomalous micellization behavior and composition heterogeneity of a triblock ABA copolymer of (A) ethylene oxide and (B) propylene oxide in aqueous solution. Macromolecules 21,2548-54(1988).
48. M. J. Schick, editor, Nonionic surfactants: physical chemistry, Marcel Dekker, Chapter 5 (1987).
49. A. Holtzer, Use of the van't Hoff relation in determination of the enthalpy of micelle formation. The Journal of Physical Chemistry 78, 1442-3 (1974).
50. D. Attwood, editor, Surfactant systems: their chemistry, pharmacy, and biology. Chapman and Hall, Chapter 3 (1983).
51. H. Ai,C. Flask,B. Weinberg,X. Shuai,M. D. Pagel,D. Farrell,J. Duerk and J.Gao, Magnetite-Loaded Polymeric Micelles as Ultrasensitive Magmetic-Resonance Probes. Advances Materials,17,1949-1952 (2005).
52. A.Halperin, Polymeric micelles: a star model. Macromolecules 20, 2943-6 (1987).
53. L. Liebert, editor, Solid State Physics, Supplement 14, Academic Press (1978).
54. S. Förster, M. Zisenis, E. Wenz, and M. Antonietti, Micellization of strongly segregated block copolymers. The Journal of Chemical Physics 104, 9956-9970 (1996).
55. P. Alexandridis and B. Lindman, Amphiphilic Block Copolymers Self-Assembly and Applications, First edition, Elsevier Science, Chapter 2 (2000).