在早年的研究中，具結晶性的聚酸酐高分子是一種曾被應用於紡織工業的一種高分子材料。然而，因為此材料在室溫環境下水氣安定性不佳的緣故，大大地限制了這個材料的應用。在約二十年前，許多的研究人員將具有這項遇水分解特性的一系列聚酸酐高分子材料，應用於生物可分解性高分子，並使用於藥物釋放控制系統中。同時也做了一系列相關的基礎及應用研究，並於生醫、生化、材料、及高分子等相關領域中得到相當多豐碩的成果。
在這一系列的實驗中，使用了癸二酸經過酸酐化反應及熔融縮合聚合反應合成聚癸二酸酐材料。實驗中嘗試以共聚合的方式將親水性高分子－聚乙二醇導入聚癸二酸酐材料中，並分析這些材料的結構、結晶性、相行為、及材料之黏彈行為，並比較這些材料的物理特性，以提供進一步之基礎研究或材料應用更多的相關資訊。合成材料之儲存安定性可經由膠體滲透層析儀及微分熱差掃描卡計分析其降解行為而得到相關之資訊。合成之聚癸二酸酐－聚乙二醇共聚合物材料於緩衝溶液中的分解行為經由電子顯微鏡觀察材料之斷裂面後也可得到，證實有別於聚酸酐材料的「表面侵蝕」而為「表層侵蝕」行為。另外，雖然合成之共聚合材料之侵蝕行為已經有明顯的改變，此類材料也仍能在中性及酸性的緩衝溶液中保持著穩定的材料分解行為。實驗中也嘗試使用合成之聚癸二酸酐高分子及聚癸二酸酐－聚乙二醇共聚合物材料分別包覆疏水性模擬藥物－對硝基苯胺及親水性模擬藥物－染色劑brilliant blue G，對材料與藥物間相行為及作用力做分析，並將所得之結果與模擬藥物的釋放行為進行比較，並探討此類合成之高分子材料在藥物釋放控制系統上之應用價值。

Crystalline polymers of polyanhydrides in the past were applied in textile industry, however, the application was limited due to their property of water sensitivity at room temperature. In 1980s, polyanhydrides were used for drug delivery system with broad potential usage. These materials, as well as their degradation products, are not only degradable but also highly biocompatible as has been demonstrated by tissue response and toxicological study.
In the preliminary study, poly(sebacic anhydride) was synthesized via melt-condensation. In addition, poly(ethylene glycol) was introduced into poly(sebacic anhydride) system via melt condensation process for the purpose to adjust the hydrophilicity to induce the applications of polyanhydride system. Crystallinity, phase behavior, and visco-behavior of these synthesized poly(sebacic anhydride-co-ethylene glycol) were investigated and discussed. These results may provide information for further studies or applications. Storage stability of synthesized materials was studied using gel permeation chromatography and differential scanning calorimeter to analyze their depolymerization behavior. Erosion and degradation behaviors of copolymers in buffers were observed by scanning electron microscope and examined by weight residual analysis. It was found that surface erosion behavior was replaced by surface-layer erosion with poly(ethylene glycol) introduced into polyanhydride system, however, stable degradation rate of polymeric matrix was still kept. These synthesized copolymers were also tested for encapsulation of modeling drugs, p-nitroaniline (hydrophobic) and Brilliant Blue G (hydrophilic). Phase behavior and polymer-drug interaction was studied, and discussed with drug releasing behavior in neutral and acidic buffers at pH 7.4 and 4.0.

Anastasiou TJ, Uhrich KE. “Novel polyanhydrides with enhanced thermal and solubility properties”, Macromolecules 33, 6217-6221, 2000.
Brannon-Peppas L. “Polymers in Controlled Drug Delivery”, Med Plast Biomater, 34-45, Nov. 1997.
Braun AG, Buckner CA, Emerson DJ, Nichinson BB. “Quantitative correspondence between the invivo and invitro activity of teratogenic agents”, Proc Natl Acad Sci USA; Biol Sci 79, 2056-2060, 1982.
Brem H, Tamargo RJ, Pinn M, Chasin M. Am Assoc Neurol Surg 381, 1988a.
Brem H, Ahn H, Tamargo RJ, Pinn M, Chasin M. Am Assoc Neurol Surg 349, 1988b.
Brem H, Epstein JI, Domb A, Tamargo RJ, Kader A, Leong KW, Langer R. “Biocompatibility of a biodegradable, controlled-release polymer in the rabbit brain”, Selective Cancer Ther 5, 55-65, 1989.
Brem H. “Polymers to treat brain-tumors”, Biomaterials 11, 699-701, 1990.
Brem H, Domb A, Lenartz D, Dureza C, Olivi A, Epstein JI. “Brain biocompatibility of a biodegradable controlled release polymer consisting of anhydride copolymer of fatty-acid dimer and sebacic acid”, J Control Release 19, 325-329, 1992.
Brus J, Dybel J, Schmidt P, Kratochvil J, Baldrain J. “Order and mobility in polycarbonate-poly(ethylene oxide) blends studied by solid-state NMR and other techniques”, Macromolecules 33, 6448-6459, 2000.
Bucher JE, Slade WC. “The anhydrides of isophathalic and terephthalic acids”, J Am Chem Soc 31, 1319-1321, 1909.
Chasin M, Langer R. “Biodegradable Polymers as Drug Delivery Systems”, Marcel Dekker, Inc., New York, 1990.
Chan C-K, Chu I-M. “Effect of hydrogen bonding on the glass transition behavior of poly(acrylic acid)/silica hybrid materials prepared by sol-gel process”, Polymer 42, 6089-6093, 2001a.
Chan C-K, Chu I-M. “Phase behavior and molecular chain environment of organic-inorganic hybrid materials based on poly(n-butyl methacrylate-co-(3-(methacryloxypropyl)) trimethoxysilane)”, Polymer 42, 6823-6831, 2001b.
Chanda M, Roy SK. “Plastics Technology Handbook”, Marcel Dekker, Inc., New York, 1998.
Chasin M, Langer R. “Biodegradable polymers as drug deliver systems”, Marcel Dekker, Inc., New York, 1990.
Chu PP, Huang J-M, Wu H-D, Chiang C-R, Chang F-C. “Molecular dynamic and mechanical properties correlations of PA6/PPO blends compatiblilized with SMA”, J Polym Sci: Polym Phys 35, 1155-1163, 1999.
Clauss J, Schmidt-Rohr K, Adam A, Boeffel C, Spiess HW. “Stiff macromolecules with aliphatic side chains: Side chain mobility, conformation, and organization from 2D solid-state NMR spectroscopy”, Macromolecules 25, 5208-5214, 1992.
Clemson Advisory Board for Biomaterials, “Definition of the word biomaterial”, The 6th Annnal Intermalionel Biomaterial Symposium, April 20-24, 1974.
Conix A. “Aromatic polyanhydrides, a new class of high melting fiber-forming polymers”, J Polym Sci 29, 343-353, 1958.
Conix A. “Poly[1,3-bis(p-carboxyphenoxy)-propane anhydride]”, Macro Synth 2, 95-98, 1966.
Dang W, Daviau T, Brem H. “Morphological characterization of polyanhydride biodegradable implant Gliadel during in vitro and in vivo erosion using scanning electron microscopy”, Pharm Res 13, 683-691, 1996.
Domb AJ, Langer R. “Polyahydirdes. I. Preparation of high molecular weight polyanhydrides”, J Polym Sci: Polym Chem 25, 3373-3386, 1987.
Domb AJ, Langer R. “Solid-state and solution stability of poly(anhydrides) and poly(ester)”, Macromolecules 22, 2117-2122, 1989.
Domb AJ, Rock M, Perkin C, Yipchuck G, Broxup B, Villemure JG. “Excretion of a radiolabelled anticancer biodegradable polymeric implant from the rabbit brain”, Biomaterials 16, 1069-1072, 1995.
Shen E, Pizsczek R, Dziadul B, Narasimhan B. “Microphase separation in bioerodible copolymers for drug delivery”, Biomaterials 22, 201-210, 2001.
Feng H, Han Y, Huang L. “Polymers and Biomaterials; Proceedings of the Syposia E: Advanced Engineering Plastics, F: Functional Polymers, and L: Biomedical Materials of the C-MRS International 1990 Conference”, Vol. 3, Elsevier Science Publisher, North-Holland, 1991. (part 3).
Feng H, Shi L, Feng Z. “Microstructure analysis of three segmented copolymers containing polydimethylsiloxane by solid-state high-resolution NMR”, Makromol Chem 194, 2257-2266, 1993.
Gedde UW. “Polymer physics”, Chapman & Hall, London, 1995. (chapter 7).
Georgi U, Brendler E, Görz H, Roewer G. “Chemical modification of thin silica films via the sol-gel-process”, J Sol-Gel Sci Technol 8, 507, 1997.
Hatakeyama T, Quinn FX. “Thermal Analysis”, John Wiley & Sons, New York, 1994. (chapter 6).
Hill JW. “Studies on polymerization and ring formation. VI. Adipic anhydride”, J Am Chem Soc 52, 4110-4114, 1930.
Hill JW, Carothers WH. “Studies of polymerization and ring formation. XIV. A linear superpolyanhydride and a cyclic dimeric anhydride from sebacic acid”, J Am Chem Soc 54, 1569-1579, 1932a.
Hill JW, Carothers WH. “Studies of polymerization and ring formation. XV. Artificial fibers from synthetic linear condensation superpolymers”, J Am Chem Soc 54, 1579, 1932b.
Hollinger JO. “Biomedical applications of Synthetic Biodegradable Polymers”, CRC Press, Inc., Boca Raton, 1995.
Kanai M, Mortell KH, Kiessling LL. “Varying the size of multivalent ligands: The dependence of concanavalin a binding on neoglycopolymer length”, J Am Chem Soc 119, 9931, 1997.
Kiessling LL, Pohl NL. Chem Biol 3, 71, 1996.
Lanza RP, Langer R, Vacanti J. “Principles of tissue engineering”, 2nd Ed., Academic Press, San Diego, 2000.
Leong KW, Brott BC, Langer R. “Bioerodible polyanhydrides as drug-carrier matrices. I. Characterization, degradation, and release characteristics”, J Biomed Mater Res 19, 941-955, 1985.
Leong KW, D’Amore P, Marletta M, Langer R. “Bioerodible polyanhydrides as drug-carrier matrices. II. Biocompatibility and chemical reactivity”, J Biomed Mater Res 20, 51-64, 1986.
Mathias LJ. “Solid state NMR of polymers”, Plenum Press, New York, 1988.
Mathiowitz E, Saltzman WM, Domb A, Langer R. “Polyanhydride microspheres as drug carriers. II. Microencapsulation by solvent removal”, J Appl Polym Sci 35, 755-774, 1988.
Mathiowitz E, Amato C, Dor Ph., Langer R. “Polyanhydride microspheres: 3. Morphology and characterization of systems made by solvent removal”, Polymer 31, 547-555, 1990.
Mathiowitz E, Bernstein H, Ciannos S, Dor P, Turek T, Langer R. “Polyanhydride microspheres. IV. Morphology and characterization of systems made by spray drying”, J Appl Polym Sci 45, 125-134, 1992.
McBrierty VJ, Packer KJ. “Nuclear magnetic resonance in solid polymers”, Cambridge University Press, Great Britain, 1993.
Mylonas CC, Tabata Y, Langer R, Zohar Y. “Preparation and evaluation of polyanhydride microspheres containing gonadotropin-releasing hormone (GnRH), for inducing ovulation and spermiation in fish”, J Control Release 35, 23-34, 1995.
Park E-S, Maniar M, Shah J. “Effects of model compounds with varying physicochemical properties on erosion of polyanhydride devices”, J Control Release 40, 55-65, 1996a.
Park E, Maniar M, Shah J. “Water uptake in to polyanhydride devices: kinetics of uptake and effects of model compounds incorporated, and device geometry on water uptake” J Control Release 40, 111-121, 1996b.
Park E-S, Maniar M, Shah JC. “Influence of physicochemical properties of model compounds on their release from biodegradable polyanhydride devices”, J Control Release 48, 67-78, 1997.
Park E-S, Maniar M, Shah JC. “Biodegradable polyanhydride devices of cefazolin sodium, bupivacaine, and taxol for local drug delivery: preparation, and kinetics and mechanism of in vitro release”, J Control Release 52, 179-189, 1998.
Penning JP, St John Manley R. “Miscible blends of two crystalline polymers. 1. Phase behavior and miscibility in blends of poly(vinylidene fluoride) and poly(1,4-butylene adipate)”, Macromolecules 29, 77-83, 1996.
Peppas NA, Langer RS. “Advances in Polymer Science, 107; Biopolymers I”, Springer-Verlag, Berlin, 1993.
Rock M, Green M, Fait C, Geil R, Myer J, Maniar M, Domb A. Polym Preprints 32, 221, 1991.
Rosen HB, Chang J, Langer R, Linhardt RJ, Wnek GE. “Bioerodible polyanhydrides for controlled drug delivery”, Biomaterials 4, 131-133, 1983.
Schmidt-Rohr K, Clauss J, Spiess HW. “Correlation of structure, mobility, and morphological information in heterogeneous polymer materials by two-dimensional wideline-separation NMR spectroscopy”, Macromolecules 25, 3273-3277, 1992
Shieh L, Tamada J, Chen I, Pang J, Domb A, Langer R. “Erosion of a new family of biodegradable polyanhydrides”, J Biomed Mater Res 28, 1465-1475, 1994.
Skrovanek DJ, Howe SE, Painter PC, Coleman MM. “Hydrogen bonding in polymers: infrared temperature studies of an amorphous polyamide”, Macromolecules 18, 1676-1683, 1985.
Socrates G. “Infrared characteristic group frequencies”, A Wiley- Interscience publication, Great Britain, 1980. (chapter 10).
Sperling LH, “Introduction to physical polymer science”, 2nd Ed., John Wiley & Sons, Singapore, 1992. (chapter 6).
Tanida F, Tojima T, Han S-M, Nishi N, Tokura S, Sakairi N, Seino H, Hamada K. “Novel synthesis of a water-soluble cyclodextrin-polymer having a chitosan skeleton”, Polymer 39, 5261-5263, 1998.
Uhrich KE, Gupta A, Thomas TT, Laurencin CT, Langer R. “Synthesis and characterization of degradable poly(anhydride-co-imides)”, Macromolecules 28, 2184-2193, 1995.
Uhrich KE, Thomas TT, Laurencin CT, Langer R. “In vitro degradation characteristics of poly(anhydride-imides) containing trimellitylimidoglycine”, J Appl Polym Sci 63, 1401-1411, 1997.
Wang F-Y, Ma C-CM, Wu H-D. “Hydrogen bonding in polyamide toughened novolac type phenolic resin”, J Appl Polym Sci 74, 2283-2289, 1999.
Wang F-Y, Ma C-CM, Hung AYC, Wu H-D. “The interassociation equilibrium constant and thermodynamic properties of phenolic resin/polyamide 6 blend”, Macromol Chem Phys 202, 2328-2334, 2001.
Wu H-D, Ma C-CM, Chu PP, Tseng H-T, Lee C-T. “The phase behaviour of novolac type phenolic resin blended with poly(adipic ester)”, Polymer 39, 2859-2865, 1998.
Wu MP, Tamada JA, Brem H, Langer R. “In vivo versus in vitro degradation of controlled release polymers for intracranial surgical therapy”, J Biomed Mater Res 28, 387-395, 1994.
Yasugi K, Nakamura T, Nagasaki Y, Kato M, Kataoka K. “Sugar-installed polymer micelles: Synthesis and micellization of poly(ethylene glycol)-poly(D,L-lactide) block copolymers having suger groups at the PEG chain end”, Macromolecules 32, 8024-8032, 1999.
Yoda N. “Syntheses of polyanhydrides. XII. Crystalline and high melting polyamidepolyanhydride of methylenebis(p-carboxyphenyl)amide”, J Polym Sci 1, 1323-1338, 1963.