聚酸酐高分子之合成、降解及藥物釋放｜國立清華大學博碩士論文庫

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研究生：	李玟娟 Wen-Chuan Lee
論文名稱：	聚酸酐高分子之合成、降解及藥物釋放 Preparation, Degradation Behavior, and Drug Release of Polyanhydrides
指導教授：	朱一民 I-Ming Chu
口試委員:
學位類別：	博士 Doctor
系所名稱：	工學院 - 化學工程學系 Department of Chemical Engineering
論文出版年：	2007
畢業學年度：	95
語文別：	中文
論文頁數：	94
中文關鍵詞：	聚酸酐、生物可降解性、藥物控制釋放、奈米顆粒
外文關鍵詞：	polyanhydrides, biodegradability, drug controlled release, nanoparticles
相關次數：	點閱：2 下載：0
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在過去的研究當中，由於聚酸酐具有高度的生物分解性以及生物相容性，常應用在開發藥物釋放系統。聚酸酐的降解過程為表面侵蝕行為，而這樣的降解方式正適用於藥物釋放系統。隨著奈米技術的開發，越來越多的奈米藥物載體被應用在藥物釋放上面。然而，在這樣微小的尺度，藥物載體的比表面積急遽增加，聚酸酐的降解行為將產生改變，進而牽動藥物釋放行為。因此，本研究利用1,3-雙（對羧基苯氧基）丙烷（1,3-bis(p-carboxyphenoxy)propane, CPP）及癸二酸（sebacic acid, SA）兩類的雙酸單體，利用熔融縮合法進行聚合，形成癸二酸之單聚物（homopolymer）以及共合成之共聚物（copolymer）。利用溶劑置換法（solvent displacement）以及乳化法（emulsification）將聚合物製備形成奈米顆粒，進行降解以及包覆藥物釋放等實驗。此外，錠狀的聚合物亦進行了相同的降解實驗，以進行比較。
由研究結果得知，聚酸酐聚合物可透過此兩種方式，改變聚合物濃度、介面活性劑種類等變因製備出粒徑約在200 nm上下的奈米顆粒。這些奈米顆粒相較於錠狀結構有著快速的降解行為，以癸二酸單聚物而言，錠狀降解時間需時約兩星期，而奈米顆粒的降解時間則在一星期上下，除了比表面積的差異之外，微小化程序以及製備奈米顆粒的方法使得癸二酸的鏈段的結晶度下降亦扮演著相當重要的角色，而加入更具疏水特性的1,3-雙（對羧基苯氧基）丙烷共聚物並非使材料防止水的滲透而不易降解，反而亦抑制了癸二酸的鏈段的結晶，使奈米顆粒的降解時間縮短至兩天。
在包覆藥物方面，喜樹鹼（camptothecin）及紫杉醇（paclitaxel）為測試的疏水性藥物。藥物初始的劑量直接影響了藥物負載的效率，藥物包覆量與顆粒大小呈現正相關，顯示藥物佔據了載體本身的體積。紫杉醇的包覆效率可達藥物載體的10％以上，顯示紫杉醇可順利包覆於聚酸酐材料中。根據包覆喜樹鹼的實驗，奈米顆粒的製備的方式對於藥物的包覆量及釋放行為影響不大，但對於藥物載體降解的行為則有明顯的差異，溶劑置換法所製備出來的奈米顆粒呈現快速的降解而乳化法的降解行為則較為緩慢。此外，不管是何種製備奈米顆粒方式，藥物釋放的行為與藥物載體的降解情形有顯著的不一致性，藥物的釋放速度均較藥物載體降解速度快，藥物於2-3日內則釋放完畢，而載體則為3-4日甚至更久。除了藥物載體製備方式、製備過程中的溶劑揮發可能造成藥物漏失，藥物本身對於材料結晶行為的影響，亦是影響藥物釋放及載體降解行為的重要因素。

Polyanhydrides have been used in many drug delivery systems due to their biodegradability and biocompatibility. Their degradation pattern of surface erosion made them suitable for stable drug release applications. However, in nanoparticle systems, this degradation pattern may not hold, and the drug release kinetics will be different also. In this study, 1,3-bis(p-carboxyphenoxy)propane (CPP) and sebacic acid (SA) were synthesized through melt-condensation into homopolymers and copolymers to investigate the different degradation patterns and drug release mechanisms of disk and nanoparticle.
By solvent displacement and emulsification methods, the polymers were prepared into the nanoparticles with dimension in 200 nm through changing polymer concentrations, and verifying surfactants. PSA disks degraded for about two weeks wile nanoparticles displayed a fast degradation in about one week, depending on the preparation method. Besides the large differences of surface area to volume ratio between disks and nanoparticles, the micronization of the samples and nanoparticles preparation methods inducing decrease of the crystallinity of SA segments of these nanoparticles were important factors of tailoring degradation rates. The copolymers contained with hydrophobic segment of CPP did not preventing water penetrating into the samples to hinder hydrolysis but hindered the crystallization of SA segments, which resulting fast degradation of these nanoparticles.
Camptothecin and paclitaxel, the highly hydrophobic anticancer drugs, were used as modeling drugs. The initial drug loading directly affected the drug loading efficiencies, and also the size of the nanoparticles. The results revealed that drugs themselves occupied the space in the nanoparticles. The drug loading efficiencies of the paclitaxel were over 10% based on polymer weight, which indicating polyanhydrides suitable for encapsulating paclitaxel. In the exams of encapsulation with camptothecin, the drug loading efficiencies and drug release mechanism were independent on the preparation methods. However, the preparation methods dominated the degradation of nanoparticles. The drug release of the nanoparticles all demonstrated an initial burst. In the meantime, the degradation of nanoparticles and drug release displayed significantly inconsistent, i.e. the drug release rates were faster then the nanoparticles degradation rates, the drug released in 2-3 days while degradation lasted for 3-4 days even longer. Besides the preparation methods of nanoparticles, the solvent evaporation procedure, the drug affecting polymer crystallization were also important factors on drug release and nanoparticle degradation.

   Introduction                                                         1
1    Biomaterials                                                        2
2    Biodegradable polymers                                            3
3    Polyanhydrides                                                    5
3.1    A brief history                                                7
3.2    Synthesis methods                                            8
3.3    Degradation                                                    9
3.4    The biocompatibility                                           10
3.5    The applications                                               12
4    Drug controlled release systems                                       13
5    Nanoparticles                                                       15
6    Objectives                                                       16

   Preparation, Characterization and Biodegradation of Polyanhydrides       17
1    Backgrounds                                                       18
2    Experimental Parts                                                   19
2.1    Materials                                                   19
2.2    Methods                                                   19
2.2.1    Synthesis of 1,3-bis(p-carboxyphenoxy) propane (CPP)               19
2.2.2    Polymer synthesis                                           21
2.2.3    Characterization of polymers                                   22
2.2.4    Degradation of polyanhydrides                                   22
3    Results and Discussions                                           24
3.1    The synthesis and characterization of the polymers                   24
3.2    The degradation of polyanhydrides                               28
4    Conclusions                                                       31

   Preparation of Polyanhydrides Nanoparticles as Hydrophobic Drug Carrier by Solvent Displacement Process                                       33
1    Backgrounds                                                       34
2    Experimental Parts                                                   37
2.1    Materials                                                   37
2.2    Methods                                                   37
2.2.1    Preparation of nanoparticles                                   37
2.2.2    Hydrophobic drug encapsulated in nanoparticles                   37
2.2.3    Characterization of nanoparticles                               37
2.2.4    Drug loading and encapsulation efficiency                       38
2.2.5    Degradation and drug release study                               39
3    Results and Discussions                                           39
3.1    Nanoparticle properties                                       39
3.2    Degradation of nanoparticles                                   43
3.3    Drug loading and encapsulation efficiency                           45
3.4    In vitro release                                               46
4    Conclusions                                                       47

   Preparation of Polyanhydrides Nanoparticles as Hydrophobic Drug Carrier by Emulsification Evaporation Process                               49
1    Backgrounds                                                       50
2    Experimental Parts                                                   51
2.1    Materials                                                   51
2.2    Methods                                                   52
2.2.1    Preparation of Nanoparticles                                   52
2.2.2    Hydrophobic drugs encapsulated in nanoparticles                   53
2.2.3    Particles characterization                                       53
2.2.4    Recovery rate, drug loading and encapsulation efficiency           53
2.2.5    In vitro study                                               55
3    Results and Discussions                                           55
3.1    Nanoparticle properties                                       55
3.2    Degradation of nanoparticles                                   61
3.3    The encapsulation of camptothecin                               63
3.4    In vitro study of releasing camptothecin                           65
3.5    The encapsulation of paclitaxel                                   68
3.6    In vitro study of releasing paclitaxel                               69
4    Conclusions                                                       72

   Summary                                                           74

Appendixes                                                           81

References                                                           85

                                

1. Definition of the word biomaterials. 1974, April 20-24. Clemson Advisory Board for Biomaterials.
2. Fu J, Fiegel J, Krauland E, Hanes J. New polymeric carriers for controlled drug delivery following inhalation or injection. Biomaterials 2002;23:4425-4433.
3. Ikada Y, Tsuji H. Biodegradable polyesters for medical and ecological applications. Macromolecular Rapid Communications 2000;21:117-132.
4. Leenslag JW, Pennings AJ, Bos RR, Rozema FR, Boering G. Resorbable materials of poly(L-lactide). Biomaterials 1987;8:70-73.
5. Hubbell JA. Hydrogel systems for barriers and local drug delivery in the control of wound healing. Journal of Controlled Release 1996;39:305-313.
6. Chen G, Ushida T, Tateishi T. Hybrid biomaterials for tissue engineering:A preparative method for PLA or PLGA collagen hybrid sponges. Advanced Materials 2000;12:455-457.
7. Heller J, Barr J, Ng, S.Y., Abdellauoi KS, Gurny R. Poly(ortho esters): synthesis, characterization, properties and uses. Advanced Drug Delivery Reviews 2002;54:1015-1039.
8. Kumar N, Langer R, Domb AJ. Polyanhydrides: an overview. Advanced Drug Delivery Reviews 2002;54:889-910.
9. Vauthier C, Dubernet C, Fattal E, Pinto-Alphandary H, Couvreur P. Poly(alkylcyanoacrylates) as biodegradable materials for biomedical applications. Advanced Drug Delivery Reviews 2003;55:519-548.
10. Jain RA. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials 2000;21:2475-2490.
11. Lakshmi S, Katti DS, Laurencin CT. Biodegradable polyphosphazenes for drug delivery applications. Advanced Drug Delivery Reviews 2003;55:467-482.
12. Bourke SL, Kohn J. Polymers derived from the amino acid L-tyrosine: polycarbonates, polyarylates and copolymers with poly(ethylene glycol). Advanced Drug Delivery Reviews 2003;55:447-466.
13. Uhrich KE, Larrier DR, Laurencin CT, Langer R. In Vitro Degradation Characteristics of Poly(Anhydride-Imides) Containing Pyromellitylimidoalanine. Journal of Polymer Science Part A: Polymer Chemistry 1996;34:1261-1269.
14. Jain JP, Modi S, Domb AJ, Kumar N. Role of polyanhydrides as localized drug carriers. Journal of Controlled Release 2005;103:541-563.
15. Domb AJ, Langer R. Polyanhydrides. I. Preparation of high molecular weight polyanhydrides. Journal of Polymer Science Part A: Polymer Chemistry 1987;25:3373-3386.
16. Akbari H, D'Emanuele A, Attwood D. Effect of geometry on the erosion characteristics of polyanhydride matrixes. International Journal of Pharmaceutics 1998;160:83-89.
17. Göpferich A, Langer R. Modeling of Polymer Erosion. Macromolecules 1993;26:4105-4112.
18. Bucher JE, Slade WC. The anhydrides of isophthalic and terephthalic acids. Journal of the American Chemical Society 1909;31:1319-1325.
19. Hill JW. Studies on polymerization and ring formation. Vi. Adipic anhydride. Journal of the American Chemical Society 1930;52:4110-4114.
20. Hill JW, Carothers WH. Studies of polymerization and ring formation. XIV. A linear superpolyanhydride and a cyclic dimeric anhydride from sebacic acid. Journal of the American Chemical Society 1932;54:1569-1579.
21. Conix A. Aromatic polyanhydrides, a new class of high melting fiber-forming polymers. Journal of Polymer Science 1958;29:343-353.
22. Yoda N. Journal of Polymer Science: Part A Polymer Chemistry 1962;1:1323.
23. Rosen HB, Chang J, Wnek GE, Linhardt RJ, Langer R. Bioerodible polyanhydrides for controlled drug delivery. Biomaterials 1983;4:131-133.
24. Leong K, Simonte V, Langer R. The synthesis of polyanhydrides: melt polycondensation, dehydrochlorination, and dehydrated coupling. Macromolecules 1987;20:705-712.
25. Katti DS, Lakshmi S, Langer R, Laurencin CT. Toxicity, biodegradation and elimination of polyanhydrides. Advanced Drug Delivery Reviews 2002;54:933-961.
26. Leong KW, Brott BC, Langer R. Bioerodible polyanhydrides as drug-carrier matrices. I: Characterization, degradation, and release characteristics. Journal of Biomedical Materials Research 1985;19:941-955.
27. Park E, Maniar M, Shah J. Effect of model compounds with varying physicochemical properties on erosion of polyanhydride devices. Journal of Controlled Release 1996;40:111-121.
28. Domb AJ, Nudelman R. In vivo and in vitro elimination of aliphatic polyanhydrides. Biomaterials 1995;16:319-323.
29. Mathiowitz E, Ron E, Mathiowitz G, Amato C, Langer R. Morphological Characterization of Bioerodible Polymers. 1. Crystallinity of Polyanhydride Copolymers. Macromolecules 1990;23:3212-3218.
30. Shieh L, Tamada J, Chen I, Pang J, Domb AJ, Langer R. Erosion of a new family of biodegradable polyanhydrides. Journal of Biomedical Materials Research 1994;28:1465-1475.
31. Kipper MJ, Seifert S, Thiyagarajan P, Narasimhan B. Understanding polyanhydride blend phase behavior using scattering, microscopy, and molecular simulations. Polymer 2004;45:3329-3340.
32. Mu L, Feng SS. A novel controlled release formulation for the anticancer drug paclitaxel (Taxol): PLGA nanoparticles containing vitamin E TPGS. Journal of Controlled Release 2003;86:33-48.
33. Kipper M, Shen E, Determan A, Narasimhan B. Design of an injectable system based on bioerodible polyanhydride microspheres for sustained drug delivery. Biomaterials 2002;23:4405-4412.
34. McCann DL, Heatley F, D'Emanuele A. Characterization of chemical structure and morphology of eroding polyanhydride copolymers by liquid-state and solid-state 1H n.m.r. Polymer 1999;40:2151-2162.
35. Uhrich K, Gupta A, Thomas T, Laurencin C, Langer R. Synthesis and characterization of degradable poly(anhydride-coimides). Macromolecules 1995;28:2184-2193.
36. Domb AJ, Langer R. Solid-state and solution stability of poly(anhydrides) and poly(esters). Macromolecules 1989;22:2117-2122.
37. Leong KW, D'Amore P, Langer R. Bioerodible polyanhydrides as drug-carrier matrices: II. Biocompatibility and chemical reactivity. Journal of Biomedical Materials Research 1986;20:51-64.
38. Laurencin C, Domb AJ, Morris C, Brown V, Chasin M, McConnell R, Lange N, Langer R. Poly(anhydride) administration in high doses in vivo: studies of biocompatibility and toxicology. Journal of Biomedical Materials Research 1990;24:1463-1481.
39. Domb AJ, Rock M, Schwartz J, Perkin C, Yipchuk G, Broxup B, Villemure JG. Metabolic disposition and elimination studies of a radiolabelled biodegradable polymeric implant in the rat brain. Biomaterials 1994;15:681-688.
40. Albertsson A-C, Carlfors J, Sturesson C. Preparation and characterization of poly(adipic anhydride) microspheres for ocular drug delivery. Journal of Applied Polymer Science 1996;62:695-705.
41. Wu C, Fu J, Zhao Y. Novel Nanoparticles Formed via Self-Assembly of Poly(ethylene glycol-b-sebacic anhydride) and Their Degradation in Water. Macromolecules 2000;33:9040-9043.
42. Masters DB, Berde CB, Dutta S, Turek T, Langer R. Sustained local-anesthetic release from bioerodible polymer matrices-a potential method for prolonged regional anesthesia. Pharmaceutical Research 1993;10:1527-1532.
43. Brem H, Ewend MG, Piantadosi S, Greenhoot J, P.C.Burger, Sisti M. The safety of interstitial chemotherapy with BCNU-loaded polymer followed by radiation therapy in the treatment of newly diagnosed malignant gliomas: phase I trial. Journal of Neuro-Oncology 1995;26:111-123.
44. Brem H, Lawson HC. The development of new brain tumor therapy utilizing the local and sustained delivery of chemotherapeutic agents from biodegradable polymers Cancer 1999;86:197-199.
45. Stephens D, Li L, Robinson D, Chen S, Chang H-C, Liu RM, Tian Y, Ginsburg EJ, Gao X, Stultz T. Investigation of the in vitro release of gentamicin from a polyanhydride matrix. Journal of Controlled Release 2000;63:305-317.
46. Li LC, Deng J, Stephens D. Polyanhydride implant for antibiotic delivery-from the bench to the clinic. Advanced Drug Delivery Reviews 2002;54:963-986.
47. Fu J, Fiegel J, Hanes J. Synthesis and Characterization of PEG-Based Ether-Anhydride Terpolymers: Novel Polymers for Controlled Drug Delivery. Macromolecules 2004;37:7174-7180.
48. Vogelhuber W, Spruß T, Bernhardt G, Buschauer A, pferich AG. Efficacy of BCNU and paclitaxel loaded subcutaneous implants in the interstitial chemotherapy of U-87 MG human glioblastoma xenografts. International Journal of Pharmaceutics 2002;238:111-121.
49. Krasko MY, Shikanov A, Ezra A, Domb AJ. Poly(ester anhydride)s Prepared by the Insertion of Ricinoleic Acid into Poly(sebacic acid). Journal of Polymer Science Part A: Polymer Chemistry 2003;41:1059-1069.
50. Storm B, Moriarity JL, Tyler B, Burger PC, Brem H, Weingart J. Polymer delivery of camptothecin against 9L gliosarcoma: release, distribution, and efficacy. Journal of Neuro-Oncology 2002;56:209-217.
51. Langer R. Drug delivery and targeting. Nature 1998;392(6679):5-10.
52. Advanced Drug Delivery Systems: New Developments, New Technologies: Business Communications Company Inc.; 2006 October 1.
53. Uhrich KE, Cannizzaro SM, Langer RS, Shakesheff KM. Polymeric Systems for Controlled Drug Release. Chemical Reviews 1999;99:3181-3198.
54. Kumar MNVR, Kumar N. Polymeric controlled drug-delivery systems: perspetive issue and opportunities. Drug Development and Industrial Pharmacy 2001;27:1-30.
55. Jantzen GM, Robinson JR. Modern Pharmaceutics. New York: Marcel Dekker; 1996.
56. Hunter WL, Burt HM, Machan L. Local delivery of chemotherapy: a supplement to existing cancer treatments. A case for surgical pastes and coated stents. Advanced Drug Delivery Reviews 1997;26:199-207.
57. Feng S-S, Chien S. Chemical Engineering Science. Chemotherapeutic engineering: Application and further development of chemical engineering principles for chemotherapy of cancer and other diseases 2003;58:4087-4114.
58. Feng SS, Mu L, Chen BH, Pack D. Polymeric nanospheres fabricated with natural emulsifiers for clinical administration of an anticancer drug paclitaxel (Taxol®). Material Science and Engineering C 2002;20:85-92.
59. Edwards DA, Hanes J, Caponetti G, Hrkach J, Ben-Jebria A, Eskew ML, Mintzes J, Deaver D, Lotan N, Langer R. Large Porous Particles for Pulmonary Drug Delivery. Science 1997;276:1868-1871.
60. Vila A, Gill H, McCallion O, Alonso MJ. Transport of PLA-PEG particles across the nasal mucosa: effect of particle size and PEG coating density. . Journal of Controlled Release 2004;98:231-244.
61. Couvreur P, Dubernet C, Puisieux F. Controlled drug delivery with nanoparticles: Current possibilities and future trends. European Journal of Pharmaceutics and Biopharmaceutics 1995;41:2-13.
62. Fessi H, Puisieux F, Devissaguet J, Ammoury N, Benita S. Nanocapsule formulation by interfacial polymer deposition following solvent displacement. International Journal of Pharmaceutics 1989;55:R1-R4.
63. Allémann E, Gurny R, Doelker E. Preparation of aqueous polymeric nanodispersions by a reversible salting-out process: influence of process parameters on particle size. International Journal of Pharmaceutics 1992;87:247-253.
64. Mathiowitz E, Bernstein H, Giannos S, Dor P, Turek T, Langer R. Polyanhydride microspheres: IV. Morphology and characterization of systems made by spray drying. Journal of Applied Polymer Science 1992;45:125-134.
65. Pfeifer BA, Burdick JA, Langer R. Formulation and surface modification of poly(ester-anhydride) micro- and nanospheres. Biomaterials 2005;26:117-124.
66. Fu J, Wu C. Laser light scattering study of degradation of poly(sebacic anhydride) nanoparticles. Journal of Polymer Science Part B: Polymer Physics 2001;39:703-708.
67. Domb AJ, Langer R. Poly(anhydrides). 3. Poly(anhydrides) based on aliphatic-aromatic diacids. Macromolecules 1989;22:3200-3204.
68. Domb AJ, Shastri VR, Ta-Shma Z, Masters D, Ringel I, Teomin D, Langer R. Polyanhydrides. In: Domb AJ, Kost J, Wiseman DM, editors. Handbook of Biodegradable Polymers. New York: Harwood Academic Publishers; 1997. p 135-159.
69. Conix A. Poly[1,3-bis(p-carboxyphenoxy)-propane anhydride]. In: Moore JA, editor. Macromol Synth Collective. New York: Wiley; 1987. p 187-190.
70. Göpferich A, Langer R. The influence of microstructure and monomer properties on the erosion mechanism of a class of polyanhydrides. Journal of Polymer Science Part A: Polymer Chemistry 1993;31:2445-2458.
71. Göpferich A, Karydas D, Langer R. Prediction drug release from cylinderic polyanhydride matrix discs. European Journal of Pharmaceutics and Biopharmaceutics 1995;41:81-87.
72. Shen E, Kipper MJ, Dziadul B, Lim M-K, Narasimhan B. Mechanistic relationships between polymer microstructure and drug release kinetics in bioerdible polyanhydrides. Journal of Controlled Release 2002;82:115-125.
73. Mathiowitz E, Jacob J, Pekarek K, Chickering D. Morphological characterization of Bioerodible polymers. 3. Characterization of the erosion and intact zones in polyanhydrides using scanning electron microscopy. Macromolecules 1993;26:6756-6765.
74. Seidel J, Uhrich K, Laurencin C, Langer R. Erosion of poly(anhydride-co-imides): A preliminary mechanistic study. Journal Applied Polymer Science 1996;62:1277-1283.
75. Muggli DS, Burkoth AK, Anseth KS. Crosslinked polyanhydrides for use in orthopedic applications: Degradation behavior and mechanics. Journal of Biomedical Materials Research 1999;46:271-278.
76. D'Emanuele A, Hill J, Tamada JA, Domb AJ, Langer R. Molecular-Weight Changes in Polymer Erosion Pharmaceutical Research 1992;9:1279-1283.
77. Quintanar-Guerrero D, Allemann E, Fessi H, Doelker E. Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers. Drug Development and Industrial Pharmacy 1998;24:1113-1128.
78. Quintanar-Guerrero D, Allémann E, Doelker E, Fessi H. A mechanistic study of the formation of polymer nanoparticles by the emulsification-diffusion technique Colloid & Polymer Science 1997;275:640-647.
79. Wehrle P, Magenheim B, Benita S. The influence of process parameters on the PLA nanoparticle size distribution, evaluated by means of factorial design. European Journal of Pharmaceutics and Biopharmaceutics 1995;41:19-26.
80. Matsumoto A, Matsukawa Y, Suzuki T, Yoshino H, Kobayashi M. The polymer-alloys method as a new preparation method of biodegradable microspheres: principle and application to cisplatin-loaded microspheres. Journal of Controlled Release 1997;48:19-27.
81. Potineni A, Lynn DM, Langer R, Amiji MM. Poly(ethylene oxide)-modified poly(b-amino ester) nanoparticles as a pH-sensitive biodegradable system for paclitaxel delivery. Journal of Controlled Release 2003;86:223-234.
82. Chawla JS, Amiji MM. Biodegradable poly(e-caprolactone) nanoparticles for tumortargeted delivery of tamoxifen. International Journal of Pharmaceutics 2002;249 127-138.
83. Fu J, Li X-Y, Ng DKP, Wu C. Encapsulation of Phthalocyanines in Biodegradable Poly(sebacic anhydride) Nanoparticles. Langmuir 2002;18:3843-3847.
84. Molpeceres J, Guzman M, Aberturas MR, Chacon M, Berges L. Application of Central Composite Designs to the Preparation of Polycaprolactone Nanoparticles by Solvent Displacement. Journal of Pharmaceutical Sciences 1996;85:206-213.
85. Mosqueira VCF, Legrand P, Pinto-Alphandary H, Puisieux F, Barratt G. Poly (d,l-lactide) nanocapsule prepared by a solvent displacement process: influence of the composition on physicochemical and structural properties. Journal of Pharmaceutical Sciences 2000;89:614-626.
86. Warner DL, Burke TG. Simple and versatile high-performance liquid chromatographic method for the simultaneous quantitation of the lactone and carboxylate forms of camptothecin anticancer drugs. Journal of Chromatography B 1997;691:161-171.
87. Feng S-s, Huang G. Effects of emulsifiers on the controlled release of paclitaxel (Taxol®) from nanospheres of biodegradable polymers. Journal of Controlled Release 2001;71:53-69.
88. Detergents Properties and Applications
http://www.sigmaaldrich.com/img/assets/15402/Detergent_Selection_Table.pdf.
89. Griffin WC. Calculation of HLB Values of Non-Ionic Surfactants. Journal of the Society of Cosmetic Chemists 1954;5:249-256.
90. Erdmann L, Uhrich KE. Synthesis and degradation characteristics of salicylic acid-derived poly(anhydride-esters). Biomaterials 2000;21:1941-1946.
91. Govender T, Stolnik S, Garnett MC, Illum L, Davis SS. PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug. Journal of Controlled Release 1999;57:171-185.
92. Paul M, Laatiris A, Fessi H, Dufeu B, Durand R, Deniau M, Astier A. Pentamidine-Loaded Poly(D,L-lactide) Nanoparticles: Adsorption and Drug Release. Drug Development Research 1998;43:98-104.
93. Niwa T, Takeuchi H, Hino T, Kunou N, Kawashima Y. Preparation of biodegradable nanospheres of water soluble and insoluble drugs with D,L-lactide:glycolide copolymer by a novel spontaneous emulsification solvent diffusion method and the drug release behavior. Journal of Controlled Release 1993;25:89-98.
94. Wang J, Wang BM, Schwendeman SP. Characterization of the initial burst release of a model peptide from poly(D,L-lactide-co-glycolide) microspheres. Journal of Controlled Release 2002;82:289-307.
95. Jiang H, Chen D, Zhao P, Li Y, Zhu K. Novel Copolyanhydrides Combining Strong Inherent Fluorescence and a Wide Range of Biodegradability: Synthesis, Characterization and in vitro Degradation. Macromolecular Bioscience 2005;5:753-759.
96. Kim HK, Park TG. Microencapsulation of dissociable human growth hormone aggregates within poly(DL-lactic-co-glycolic acid) microparticles for sustained release. International Journal of Pharmaceutics 2001;229:107-116.
97. Jeffery H, Davis SS, O'Hagan DT. The preparation and characterisation of poly(lactide-co-glycolide) microparticles. I: Oil-in-water emulsion solvent evaporation. International Journal of Pharmaceutics 1991;77:169-175.
98. Scholes PD, Coombes AGA, Illum L, Davis SS, Vert M, Davies MC. The preparation of sub-200 nm poly(lactide-co-glycolide) microspheres for site-specific drug delivery. Journal of Controlled Release 1993;25:145-153.
99. Mu L, Seow P-H, Ang S-N, Feng S-S. Study on surfactant coating of polymeric nanoparticles for controlled delivery of anticancer drug. Colloid & Polymer Science 2004;283:58-65.
100. Konan YN, Gurny R, Alle´mann E. Preparation and characterization of sterile and freeze-dried sub-200 nm nanoparticles. International Journal of Pharmaceutics 2002;233:239-252.
101. Sahoo SK, Panyam J, Prabha S, Labhasetwar V. Residual polyvinyl alcohol associated with poly (D,L-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake. Journal of Controlled Release 2002;82:105-114.
102. Lee SC, Oh JT, Jang MH, Chung SI. The preparation of monodispers biodegradable polyester nanoparicles with controlled size. Journal of Biomedical Materials Research Part B 2003;66B:559-566.
103. Lee SC, Oh JT, Jang MH, Chung SI. Quantitative analysis of polyvinyl alcohol on the surface of poly(D,L-lactide-co-glycolide) microparticles prepared by solvent evaporation method: effect of particle size and PVA concentration. Journal of Controlled Release 1999;59:123-132.
104. Zambaux MF, Bonneaux F, Gref R, Maincent P, Dellacherie E, Alonso MJ, Labrude P, Vigneron C. Influence of experimental parameters on the characteristics of poly (lactic acid) nanoparticles prepared by a double emulsion method. Journal of Controlled Release 1998;50:31-40.
105. Fournier E, Dufresne MH, Smith DC, Ranger M, Leroux JC. A novel one-step drug-loading procedure for water-soluble amphiphilic nanocarriers. Pharmaceutical Research 2004;21:962-968.
106. Quintanar GD, Ganem QA, Allémann E, Fessi H, Doelker E. Influence of the stabilizer coating layer on the purification and freeze drying of poly (D,L-lactic acid) nanoparticles prepared by emulsification-diffusion technique. Journal of Microencapsulation 1998;15:107-119.
107. Hatefi A, Knight D, Amsden B. A Biodegradable Injectable Thermoplastic for Localized Camptothecin Delivery. Journal of Pharmaceutical Sciences 2004;93:1195–1204.

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