進階搜尋


  查詢北醫館藏
系統識別號 U0007-2701201022330800
論文名稱(中文) 開發肺部遞送之吸入性光敏劑微奈米乾粉
論文名稱(英文) Development of a photosensitizer entrapped in nanocarriers within the microparticle powder for pulmonary inhalation
校院名稱 臺北醫學大學
系所名稱(中) 牙醫學系碩博士班
系所名稱(英) School of Dentistry
學年度 98
學期 1
出版年 99
研究生(中文) 楊育才
研究生(英文) Yu-Tsai Yang
學號 D204094001
學位類別 博士
語文別 英文
口試日期 2010-01-14
論文頁數 129頁
口試委員 委員-郭士民
委員-陳進庭
委員-王蔚南
委員-楊正昌
指導教授-蔡翠敏
中文關鍵字 微脂體  微胞  奈米粒  光動力  微粒  噴霧乾燥   
英文關鍵字 liposome  micelle  nanoparticles  photodynamic therapy  microparticle  spray-drying  lung 
學科別分類
中文摘要 本研究目的為開發新穎之吸入性光敏劑微奈米乾粉,一種結合奈
米與微米複合劑型並包覆光敏劑血紫質(hematoporphyrin, Hp)之肺部遞送系統。本研究以吸收及螢光光譜分析方式監測血紫質於奈米包埋系統(微脂體、微胞、奈米粒)中,以最佳化的單體分散形式存在,避免因分子聚集而造成光動力效應的功效損失。研究發現微脂體、微胞、以及奈米粒這三種奈米載體均可有效降低水不溶性光敏劑Hp 的分子聚集,也均有提高光動力之效應。本研究進一步以人類肺腺癌細胞株A549 作體外模式細胞試驗,評估三種奈米包埋系統包覆光敏劑血紫質細胞之攝入能力及所引發的光動力效應。結果顯示,微胞化之光敏劑血紫質光動力效應明顯優於微脂體及奈米粒系統。因此,選擇光動力效應最高微胞化光敏劑血紫質,以噴霧乾燥之方式結合乳糖乾粉微粒包埋光敏劑血紫質微胞。藉由吸收光譜分析、單態氧產生及粒徑分析結果,噴霧乾燥後的微胞仍維持噴霧前之物化性質,且藉由電子顯微鏡結果分析微粒乾粉粒徑為2.3 ± 0.7 μm,此粒徑範圍可有效沉積肺泡。本實驗並以A549 作體外模式細胞試驗,結果也顯示出噴霧前後微胞包覆光敏劑血紫質細胞攝入能力及所引發的光動力效應皆無明顯差異,但皆明顯優於未包覆之組別。因此利用噴霧乾燥之方式結合乾粉微米及微胞為一極具潛力之肺部給藥系統。
英文摘要 The purpose of this study was to examine the properties of a new pulmonary delivery platform of microparticles containing nanocarriers in which a therapeutic photosensitizing drug, hematoporphyrin (Hp), was entrapped. Different nanocarriers including liposome, micelle and nanoparticle were used. Absorption and emission spectral analysis were used to monitor the monomeric/aggregated state of Hp in different carriers and solvent systems. The high levels of monomer Hp in the DMPC liposome, L122 micelle and PLGA nanoparticle was observed in all formulation. One of these, Hp encapsulated in L122 micelle (micellar Hp), was subsequently incorporated into lactose microparticles by spray-drying due to highest cellular uptake and photocytoxicity in human lung epithelial carcinoma A549 cells. Spectral and morphological analyses were performed on both micellar Hp, and lactose microparticles containing micellar Hp (lactose-micellar Hp) before and after dissolution of the microparticles in water. Photodynamic activity of the various Hp samples were evaluated in A549 cells using a light emitting diode (LED) device at a wavelength of 630 ± 5 nm. It was found that there were no significant differences between micellar Hp and lactose-micellar Hp on the generation of singlet oxygen. The mean particle size of the microparticles was 2.3 ± 0.7 μm which is within the sizerange for potential lung delivery. The cellular uptake of micellar Hp and lactose-micellar Hp measured on A549 cells was at least two-fold higher than those obtained with the Hp at equivalent concentrations. Micellar Hp exhibited higher cytotoxicity than Hp due to reduced formation of Hp aggregates and increased the cellar uptake. The spectral properties as well as the photodynamic activity of the micellar Hp was retained when formulated into microparticles by spray-drying. Microparticles containing micelles has the potential to deliver the micelle-encapsulated hydrophobic drugs for targeted therapy of pulmonary diseases.
論文目次 Content....................................................1
Table Captions.............................................4
Figure Captions............................................5
摘 要......................................................8
Abstract..................................................10
Chapter 1 Introduction...................................12
Chapter 2 Literature Review..............................17
2.1 Photodynamic therapy..................................17
2.2 Photosensitizer.......................................18
2.3 Nanocarrier encapsulating photosensitizers............19
2.4 Nanocarriers..........................................20
2.4.1 Liposomes...........................................21
2.4.2 Polymeric micelles..................................22
2.4.3 Nanoparticles.......................................23
2.5 Pulmonary inhalation systems..........................23
2.5.1 Effect of particle sizes on aerosol deposition......26
Chapter 3 Materials and Methods..........................27
3.1 Preparation and characterization of Hp encapsulated in nanocarriers..............................................27
3.1.1 Preparation of Hp encapsulated in liposomes.........28
3.1.2 Preparation of Hp encapsulated in micelles..........29
3.1.3 Preparation of Hp encapsulated in nanoparticles.....29
3.1.4 Characterization of nanocarrier Hp..................30
3.1.5 Cell culture testing................................34
3.2 Preparation and characterization of microparticles containing micelles encapsulating Hp......................37
3.2.1 Preparation of micellar Hp within lactose microparticle.............................................37
3.2.2 Characterization of micellar Hp within lactose microparticle.............................................38
3.2.3 Cell culture testing................................40
Chapter 4 Results........................................44
4.1 Characterization of nanocarrier Hp....................44
4.1.1 Size of nanocarrier Hp..............................44
4.1.2 Photophysical characterization of Hp in aqueous, ethanol, and nanocarrier..................................44
4.1.3 Photophysical characterization of Hp in liposomes...47
4.1.4 Photophysical characterization of Hp in micelles....48
4.1.5 Photophysical characterization of Hp in nanoparticles.............................................49
4.1.6 Singlet oxygen generation of Hp in nanocarriers.....49
4.1.7 In vitro Hp release.................................50
4.2 Cellular uptake and photocytotoxicity of free Hp and nanocarrier Hp............................................51
4.3 Characterization of Hp encapsulated in micelles within the microparticle powder..................................52
4.3.1 Drug loading and entrapment efficiency of micellar Hp........................................................52
4.3.2 Size and spectrum of micellar Hp before and after spray-drying..............................................53
4.3.3 Singlet oxygen generation of free Hp, micellar Hp and lactose-micellar Hp.......................................54
4.3.4 Optical and fluorescence microscope images of lactose-micellar Hp...............................................55
4.3.5 Size and morphology of lactose-micellar Hp..........55
4.4 Intracellular distribution of Hp fluorescence in A549 tumor cells...............................................56
4.5 Photocytotoxicity of free Hp, micellar Hp, lactose-micellar Hp...............................................56
Chapter 5 Discussions....................................58
5.1 Spectrum study of Hp encapsulated in nanocarriers.....58
5.2 Microparticles containing micellar Hp.................63
Chapter 6 Conclusions....................................68
6.1 Hp encapsulated in nanocarrier systems................68
6.2 Microparticles containing micellar Hp.................68
References................................................70
Publications.............................................127

參考文獻 1.Lambert CR, Reddi E, Spikes JD, Rodgers MAJ, Jori G. The effects of porphyrin structure and aggregation state on photosensitized processes in aqueous and micellar media. Photochem Photobiolo 1986;44(5):595-601.

2.Ehrenberg B, Malik Z, Nitzan Y. Fluorescence spectral changes of hematoporphyrin derivative upon binding to lipid vesicles, Staphylococcus aureus and Escherichia coli cells. Photochem Photobiol 1985;41(4):429-435.

3.Ehrenberg B, Gross E. The effect of liposomes' membrane composition on the binding of the photosensitizers Hpd and photofrin II. Photochem Photobiol 1988;48(4):461-466.

4.Ricchelli F. Photophysical properties of porphyrins in biological membranes. J Photochem Photobiol B 1995;29:109-118.

5.Allen. CM, Sharman. WM, Lier JEV. Current status of phthalocyanines in the photodynamic therapy of cancer. J. Porphyrins Phthalocyanines 2001;5(2):161–169.

6.Blum A, Grossweiner LI. Singlet oxygen generation by hematoporphyrin IX, uroporphyrin I and hematoporphyrin derivative at 546 nm in phosphate buffer and in the presence of egg phosphatidylcholine liposomes. Photochem Photobiol 1985;41(1):27-32.

7.Hoebeke M, Piette J, van de Vorst A. Photosensitized production of singlet oxygen by merocyanine 540 bound to liposomes. J Photochem Photobiol B 1991;9(3-4):281-294.

8.Nyman ES, Hynninen PH. Research advances in the use of tetrapyrrolic photosensitizers for photodynamic therapy. J Photochem Photobiol B 2004;73:1-28.

9.Damoiseau X, Tfibel F, Hoebeke M, Fontaine-Aupart MP. Effect of aggregation on bacteriochlorin a triplet-state formation: a laser flash photolysis study. Photochem Photobiol 2002;76(5):480-485.

10.Angeli NG, Lagorio MG, San Roman EA, Dicelio LE. Meso-substituted cationic porphyrins of biological interest. photophysical and physicochemical properties in solution and bound to liposomes. Photochem Photobiol 2000;72(1):49-56.

11.Dhami S, Rumbles G, MacRobert AJ, Phillips D. Comparative photophysical study of disulfonated aluminum phthalocyanine in unilamellar vesicles and leukemic K562 cells. Photochem Photobiol 1997;65(1):85-90.

12.Chang CC, Yang YT, Yang JC, Wu HD, Tsai T. Absorption and emission spectral shifts of rose bengal associated with DMPC liposomes. Dyes and Pigments 2008;79:170-175.

13.Suchetti CA, Durantini EN. Monomerization and photodynamic activity of Zn(II) tetraalkyltetrapyridinoporphyrazinium derivatives in AOT reverse micelles. Dyes and Pigments 2007;74:630-635.

14.Gomes AJ, Lunardi LO, Marchetti JM, Lunardi CN, Tedesco AC. Photobiological and ultrastructural studies of nanoparticles of poly(lactic-co-glycolic acid)-containing bacteriochlorophyll-a as a photosensitizer useful for PDT treatment. Drug Deliv 2005;12(3):159-164.

15.Konan YN, Berton M, Gurny R, Allemann E. Enhanced photodynamic activity of meso-tetra(4-hydroxyphenyl)porphyrin by incorporation into sub-200 nm nanoparticles. Eur J Pharm Sci 2003;18(3-4):241-249.

16.Vargas A, Pegaz B, Debefve E, Konan-Kouakou Y, Lange N, Ballini JP. Improved photodynamic activity of porphyrin loaded into nanoparticles: an in vivo evaluation using chick embryos. Int J Pharm 2004;286(1-2):131-145.

17.Ricci-Junior E, Marchetti JM. Preparation, characterization, photocytotoxicity assay of PLGA nanoparticles containing zinc (II) phthalocyanine for photodynamic therapy use. J Microencapsul 2006;23(5):523-538.

18.Bennett WD, Brown JS, Zeman KL, Hu SC, Scheuch G, Sommerer K. Targeting delivery of aerosols to different lung regions. J Aerosol Med 2002;15(2):179-188.

19.Dhand R. Future directions in aerosol therapy. Respir Care Clin North Am 2001;7(2):319-335, vii.

20.Sharma S, White D, Imondi AR, Placke ME, Vail DM, Kris MG. Development of inhalational agents for oncologic use. J Clin Oncol 2001;19(6):1839-1847.

21.Courrier HM, Butz N, Vandamme TF. Pulmonary drug delivery systems: recent developments and prospects. Crit Rev Ther Drug Carrier Syst 2002;19(4-5):425-498.

22.Gehr P, Green FH, Geiser M, Im Hof V, Lee MM, Schurch S. Airway surfactant, a primary defense barrier: mechanical and immunological aspects. J Aerosol Med 1996;9(2):163-181.

23.Tamura K, Lee CP, Smith PL, Borchardt RT. Effect of charge on oligopeptide transporter-mediated permeation of cyclic dipeptides across Caco-2 cell monolayers. Pharm Res 1996;13(11):1752-1754.

24.Schurch S, Gehr P, Im Hof V, Geiser M, Green F. Surfactant displaces particles toward the epithelium in airways and alveoli. Respir Physiol 1990;80(1):17-32.

25.Huang M, Ma Z, Khor E, Lim LY. Uptake of FITC-chitosan nanoparticles by A549 cells. Pharm Res 2002;19(10):1488-1494.

26.Russell-Jones GJ, Veitch H, Arthur L. Lectin-mediated transport of nanoparticles across Caco-2 and OK cells. Int J Pharm 1999;190(2):165-174.

27.Garrett DA, Failla ML, Sarama RJ, Craft N. Accumulation and retention of micellar beta-carotene and lutein by Caco-2 human intestinal cells. J Nutr Biochem 1999;10(10):573-581.

28.Yuan X, Ma Z, Zhou W, Niidome T, Alber S, Huang L. Lipid-mediated delivery of peptide nucleic acids to pulmonary endothelium. Biochem Biophys Res Commun 2003;302(1):6-11.

29.Smola M, Vandamme T, Sokolowski A. Nanocarriers as pulmonary drug delivery systems to treat and to diagnose respiratory and non respiratory diseases. Int J Nanomedicine 2008;3(1):1-19.

30.Sham JO, Zhang Y, Finlay WH, Roa RL. Formulation and characterization of spray-dried powders containing nanoparticles for aerosol delivery to the lung. Int J Pharm 2004;269(2):457-467.

31.Finlay WH, Gehmlich MG. Inertial sizing of aerosol inhaled from two dry powder inhalers with realistic breath patterns versus constant flow rates. Int J Pharm 2000;210(1-2):83-95.

32.Henderson BW, Dougherty TJ. How does photodynamic therapy work? Photochem Photobiol 1992;55(1):145-157.

33.Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nat Rev Cancer 2003;3(5):380-387.

34.Gerhardt SA, Lewis JW, Kliger DS, Zhang JZ, Simonis U. Effect of micelles on oxygen-quenching processes of triplet-state para-substituted tetraphenylporphyrin photosensitizers. J Phys Chem A 2003;107(15):2763-2767.

35.Ortner MA. Photodynamic therapy for cholangiocarcinoma: overview and new developments. Curr Opin Gastroenterol 2009;25(5):472-476.

36.Choi H, Lim W, Kim JE, Kim I, Jeong J, Ko Y. Cell death and intracellular distribution of hematoporphyrin in a KB cell line. Photomed Laser Surg 2009;27(3):453-460.

37.Corti L, Toniolo L, Boso C, Colaut F, Fiore D, Muzzio PC. Long-term survival of patients treated with photodynamic therapy for carcinoma in situ and early non-small-cell lung carcinoma. Lasers Surg Med 2007;39(5):394-402.

38.Liutkeviciute-Navickiene J, Mordas A, Rutkovskiene L, Bloznelyte-Plesniene L. Skin and mucosal fluorescence diagnosis with different light sources. Eur J Dermatol 2009;19(2):135-140.

39.Autiero M, Cozzolino R, Laccetti P, Marotta M, Quarto M, Riccio P. Hematoporphyrin-mediated fluorescence reflectance imaging: application to early tumor detection in vivo in small animals. Lasers Med Sci 2009;24(2):284-289.

40.Laptev R, Nisnevitch M, Siboni G, Malik Z, Firer MA. Intracellular chemiluminescence activates targeted photodynamic destruction of leukaemic cells. Br J Cancer 2006;95(2):189-196.

41.Ferro S, Ricchelli F, Mancini G, Tognon G, Jori G. Inactivation of methicillin-resistant Staphylococcus aureus (MRSA) by liposome-delivered photosensitising agents. J Photochem Photobiol B 2006;83(2):98-104.

42.Tsai T, Yang YT, Wang TH, Chien HF, Chen CT. Improved photodynamic inactivation of gram-positive bacteria using hematoporphyrin encapsulated in liposomes and micelles. Lasers Surg Med 2009;41(4):316-322.

43.Giusti JS, Santos-Pinto L, Pizzolito AC, Helmerson K, Carvalho-Filho E, Kurachi C. Antimicrobial photodynamic action on dentin using a light-emitting diode light source. Photomed Laser Surg 2008;26(4):281-287.

44.Detty MR, Gibson SL, Wagner SJ. Current clinical and preclinical photosensitizers for use in photodynamic therapy. J Med Chem 2004;47:3897-3915.

45.Castano AP, Demidovaa TN, Hamblin MR. Mechanisms in photodynamic therapy: part one—photosensitizers, photochemistry and cellular localization. Photodiagn Photodyn Ther 2004;1:279-293.

46.Das K, Dube A, Gupta PK. A spectroscopic study of photobleaching of Chlorin p6 in different environments Dyes and Pigments 2005;64(3):201-205.

47.Jang WD, Nakagishi Y, Nishiyama N, Kawauchi S, Morimoto Y, Kikuchi M. Polyion complex micelles for photodynamic therapy: incorporation of dendritic photosensitizer excitable at long wavelength relevant to improved tissue-penetrating property. J Controlled Release 2006;113(1):73-79.

48.McCarthy JR, Perez JM, Bruckner C, Weissleder R. Polymeric nanoparticle preparation that eradicates tumors. Nano Lett 2005;5(12):2552-2556.

49.Torchilin VP. Targeted pharmaceutical nanocarriers for cancer therapy and imaging. AAPS J 2007;9(2):E128-147.

50.Liu D, Mori A, Huang L. Role of liposome size and RES blockade in controlling biodistribution and tumor uptake of GM1-containing liposomes. Biochim Biophys Acta 1992;1104(1):95-101.

51.Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Controlled Release 2000;65(1-2):271-284.

52.Torchilin VP. Structure and design of polymeric surfactant-based drug delivery systems. J Controlled Release 2001;73(2-3):137-172.

53.Hofman JW, Carstens MG, van Zeeland F, Helwig C, Flesch FM, Hennink WE. Photocytotoxicity of mTHPC (temoporfin) loaded polymeric micelles mediated by lipase catalyzed degradation. Pharm Res 2008;25(9):2065-2073.

54.Vakil R, Knilans K, Andes D, Kwon GS. Combination antifungal therapy involving amphotericin B, rapamycin and 5-fluorocytosine using PEG-phospholipid micelles. Pharm Res 2008;25(9):2056-2064.

55.Opanasopit P, Yokoyama M, Watanabe M, Kawano K, Maitani Y, Okano T. Block copolymer design for camptothecin incorporation into polymeric micelles for passive tumor targeting. Pharm Res 2004;21(11):2001-2008.

56.Cai S, Vijayan K, Cheng D, Lima EM, Discher DE. Micelles of different morphologies--advantages of worm-like filomicelles of PEO-PCL in paclitaxel delivery. Pharm Res 2007;24(11):2099-2109.

57.Djordjevic J, Barch M, Uhrich KE. Polymeric micelles based on amphiphilic scorpion-like macromolecules: novel carriers for water-insoluble drugs. Pharm Res 2005;22(1):24-32.

58.Sezgin Z, Yuksel N, Baykara T. Preparation and characterization of polymeric micelles for solubilization of poorly soluble anticancer drugs. Eur J Pharm Biopharm 2006;64(3):261-268.

59.Nishiyama N, Kataoka K. Preparation and characterization of size-controlled polymeric micelle containing cis-dichlorodiammineplatinum(II) in the core. J Controlled Release 2001;74(1-3):83-94.

60.Kabanov AV, Batrakova EV, Alakhov VY. Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery. J Controlled Release 2002;82(2-3):189-212.

61.Kabanov AV, Alakov VY. Pluronic block copolymers in drug delivery: from micellar nanocontainers to biological response modifiers. Crit Rev Ther Drug Carrier Syst 2002;19:1-72.

62.Kabanov AV, Batrakova EV, Alakhov VY. Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery. J Controlled Release 2002;82(2-3):189-212.

63.Seville PC, Kellaway IW, Birchall JC. Preparation of dry powder dispersions for non-viral gene delivery by freeze-drying and spray-drying. J Gene Med 2002;4(4):428-437.

64.Li HY, Neill H, Innocent R, Seville P, Williamson I, Birchall JC. Enhanced dispersibility and deposition of spray-dried powders for pulmonary gene therapy. J Drug Target 2003;11(7):425-432.

65.Sweeney LG, Wang Z, Loebenberg R, Wong JP, Lange CF, Finlay WH. Spray-freeze-dried liposomal ciprofloxacin powder for inhaled aerosol drug delivery. Int J Pharm 2005;305(1-2):180-185.

66.Lo YL, Tsai JC, Kuo JH. Liposomes and disaccharides as carriers in spray-dried powder formulations of superoxide dismutase. J Controlled Release 2004;94(2-3):259-272.

67.Bhattarai SR, Kim SY, Jang KY, Yi HK, Lee YH, Bhattarai N. Amphiphilic triblock copolymer poly(p-dioxanone-co-L-lactide)-block-poly(ethylene glycol), enhancement of gene expression and inhibition of lung metastasis by aerosol delivery. Gene Ther 2007;14(6):476-483.

68.Amidi M, Krudys KM, Snel CJ, Crommelin DJ, Della Pasqua OE, Hennink WE. Efficacy of pulmonary insulin delivery in diabetic rats: use of a model-based approach in the evaluation of insulin powder formulations. J Controlled Release 2008;127(3):257-266.

69.French D, Edwards D, Niven R. The influence of formulation on emission, deaggregation and deposition of dry powders for inhalation. J Aerosol Sci 1996;27:769-783.

70.Steckel H, Müller B. In vitro evaluation of dry powder inhalers II: influence of carrier particle size and concentration on in vitro deposition. Int J Pharm 1997;154:31-37.

71.Labiris NR, Dolovich MB. Pulmonary drug delivery. Part II: the role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol 2003;56(6):600-612.

72.Tsapis N, Bennett D, Jackson B, Weitz DA, Edwards DA. Trojan particles: large porous carriers of nanoparticles for drug delivery. Proc Natl Acad Sci U S A 2002;99(19):12001-12005.

73.Sham J, Zhang Y, Finlay W, Lobenberg R. Formulation and characterization of spray-dried powders containing nanoparticles for aerosol delivery to the lung. Int J Pharm 2004;269(2):457-467.

74.Azarmi S, Tao X, Chen H, Wang Z, Finlay WH, Lobenberg R. Formulation and cytotoxicity of doxorubicin nanoparticles carried by dry powder aerosol particles. Int J Pharm 2006;319(1-2):155-161.

75.Rau JL. Respiratory care pharmacology, 6th ed. St. Louis: Mosby; 2002;39:Fig. 3-3.

76.Chowdhary RK, Chansarkar N, Sharif I, Hioka N, Dol
phin D. Formulation of benzoporphyrin derivatives in Pluronics. Photochem Photobiol 2003;77(3):299-303.

77.GR B. Phosphorus assay in column chromatography. J Biol Chem 1959;234:466-468.

78.Eaton DF. International Union of Pure and Applied Chemistry Organic Chemistry Division Commission on Photochemistry. Reference materials for fluorescence measurement. J Photochem Photobiol B 1988;2 (4):523-531.

79.Tronchin M, Jori G, Neumann M, Schuetz M, Saiyadpour A, Brauer HD. Sunlight-promoted photosensitizing and photophysical properties of porphyrins. First Internet Conf on Photochemistry and Photobiology, 1997;2005.

80.Kraljic I, Mohsni SE. A new method for the detection of singlet oxygen in aqueous solutions. Photochem Photobiol 1978;28:577-581.

81.Konan YN, Cerny R, Favet J, Berton M, Gurny R, Allemann E. Preparation and characterization of sterile sub-200 nm meso-tetra(4-hydroxylphenyl)porphyrin-loaded nanoparticles for photodynamic therapy. Eur J Pharm Biopharm 2003;55(1):115-124.

82.Gerhardt SA, Lewis JW, Kliger DS, Zhang JZ, Simonis U. Effect of micelles on oxygen-quenching processes of triplet-state para-substituted tetraphenylporphyrin photosensitizers. J Phys Chem A 2003;107(15):2763-2767.

83.Inbaraj JJ, Gandhidasan. R, Subramanian. S, Murugesan. R. Photogeneration of reactive oxygen species from ketocoumarins. J Photochem Photobiol A 1998;117:21-25.

84.Srivastava RC, Anand VD, Carper WR. A Fluorescence Study of Hematoporphyrin. Appl Spectrosc 1973;27(6):444-449.

85.Ricchelli F. Photophysical properties of porphyrins in biological membranes. J Photochem Photobiol B 1995;29:109-118.

86.Ehrenberg B, Gross E. The effect of liposomes' membrane composition on the binding of the photosensitizers Hpd and photofrin II. Photochem Photobiol 1988;48(4):461-466.

87.Hioka N, Chowdhary RK, Chansarkar N, Delmarre D, Sternberg E, Dolphin D. Studies of a benzoporphyrin derivative with Pluronics. Can J Chem 2002;80:1321-1326.

88.Boyle RW, Dolphin, D. Structure and biodistribution relationships of photodynamic sensitizers. Photochem Photobiol 1996;64:469-485.

89.Gomes AJ, Lunardi CN, Tedesco AC. Characterization of biodegradable poly(D,L-lactide-co-glycolide) nanoparticles loaded with bacteriochlorophyll-a for photodynamic therapy. Photomed Laser Surg 2007;25(5):428-435.

90.Grossweiner LI, Patel AS, Grossweiner JB. Type I and type II mechanisms in the photosensitized lysis of phosphatidylcholine liposomes by hematoporphyrin. Photochem Photobiol 1982;36:159-167.

91.Kessel D, Rossi E. Determinants of porphyrin-sensitized photooxidation characterized by fluorescence and absorption spectra. Photochem Photobiol 1982;35(1):37-41.

92.Chen B, Pogue BW, Hasan T. Liposomal delivery of photosensitising agents. Expert Opin Drug Deliv 2005;2(3):477-487.

93.Allen C, Maysinger D, Eisenberg A. Nano-engineering block copolymer aggregates for drug delivery. Colloids Surf B 1999;16:1-35.

94.Maysinger D, Lovric J, Eisenberg A, Savic R. Fate of micelles and quantum dots in cells. Eur J Pharm Biopharm 2007;65(3):270-281.

95.Taillefer J, Brasseur N, van Lier JE, Lenaerts V, Le Garrec D, Leroux JC. In-vitro and in-vivo evaluation of pH-responsive polymeric micelles in a photodynamic cancer therapy model. J Pharm Pharmacol 2001;53(2):155-166.

96.Shuai X, Ai H, Nasongkla N, Kim S, Gao J. Micellar carriers based on block copolymers of poly(epsilon-caprolactone) and poly(ethylene glycol) for doxorubicin delivery. J Controlled Release 2004;98(3):415-426.

97.Konan YN, Gurny R, Allemann E. State of the art in the delivery of photosensitizers for photodynamic therapy. J Photochem Photobiol B 2002;66(2):89-106.


論文全文使用權限
  • 同意授權瀏覽/列印電子全文服務,於2012-01-29起公開。


  • 若您有任何疑問,請與我們聯絡!
    臺北醫學大學 圖書館 簡莉婷
    E-mail:etds@tmu.edu.tw
    Tel:(02) 2736-1661 ext.2519
    Fax:(02) 2737-5446