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| 題名: | 玻尿酸口服給予之特性描述與體內分佈探討 |
| 作者: | 黃郁文 |
| 貢獻者: | 藥學研究所 |
| 關鍵詞: | 玻尿酸 口服 分子量 化學修飾比例 量子點 體內分佈 |
| 日期: | 2010 |
| 上傳時間: | 2010-10-21 10:29:50 (UTC+8) |
| 摘要: | 玻尿酸為一多功能之生物相容性良好之大分子聚合物，其物化特性及生理功能會受本身之分子量大小及化學修飾的影響。目前在醫藥方面欲發展玻尿酸口服藥物傳遞系統，但關於探討口服玻尿酸其特性描述及生物體內分佈的文獻並不多，因此希望對不同分子量及修飾程度的玻尿酸口服後在體內的變化作一瞭解，以期在口服藥物傳遞系統上有新的進展。
實驗首先建立一套分析玻尿酸分子量之分析方法，根據實驗結果，以玻尿酸標準品及分子篩滲透層析儀為一簡便且準確及再現性高的玻尿酸分子量分析方法。
本研究利用酵素消化得到分子量各異的玻尿酸。實驗結果發現，酵素濃度是造成酵素反應所得消化產物差異的主要影響因子，在固定的時間及酸鹼值下，只需調整玻尿酸酶之濃度即可獲得一系列不同分子量的玻尿酸。
接著利用adipic acid dihydrazide (ADH) 得到一系列不同化學修飾程度的玻尿酸。玻尿酸的羧基官能基在1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) 的催化下被ADH取代，玻尿酸的修飾程度會隨反應時間及玻尿酸與ADH、EDC的莫耳數比而不同。
以具螢光特性之量子點 (QDots) 與玻尿酸接合形成量子點玻尿酸接合物 (QDot-HA conjugates)，藉由尾靜脈注射和口服方式投予動物，以即時顯像試驗討論分子量及化學修飾比例對於玻尿酸體內分佈的影響。結果顯示：(1) 分子量較小的玻尿酸及輕度修飾比例的玻尿酸注射後會較快由體內清除，且小分子量玻尿酸在老鼠的胸部及腹部分布的量比大分子多。(2) 修飾比例低的玻尿酸注射後有較專一性的分佈，明顯集中在肝臟；修飾比例高的玻尿酸，因其特性受修飾的影響，在體內組織有較廣泛的分佈。
口服方面：(1) 小分子量玻尿酸口服後較快被腸胃道吸收；大分子玻尿酸吸收比較慢也較慢被代謝及排除。(2) 高修飾比例的玻尿酸其代謝及排除比低修飾比例的慢，在體內的停留時間較久。在頭頸部及胸部，低修飾比例的玻尿酸口服後的分佈量比高修飾比例的玻尿酸多，高修飾比例的玻尿酸則於骨盆的地方比低修飾比例的多。
因此，分子量是影響玻尿酸經由系統性給藥後體內分佈的主要因子；而影響玻尿酸口服後體內分佈差異的主要因素則是化學修飾程度。根據所要傳遞藥物的特性，我們可選擇具有適合之分子量大小及化學修飾比例的玻尿酸應用於口服藥物傳遞系統中。
Hyaluronic acid (HA) is a multifunctional biocompatible polymer, its physical and chemical properties and physiological functions will be affected by its molecular weight (MW) and chemical modification degrees. In the medical fields, the current demand is the development of HA oral drug delivery system, but the literatures about the characteristics and bio-distribution of HA in the body after oral administration were only a few. So it is important to understand the changes of HA with different MW and modification degrees in the body after oral administration, with a view to have new progress in developing HA oral drug delivery systems.
First, we established an experimental method to analyze the MW of HA. The results showed that, with the HA standards, the size exclusion chromatography was a simple, accurate and reproducible method for molecular weight analysis.
Digested by the enzyme, HA molecules could degrade into HA fragments with different MW. It was found that the enzyme concentration was the main influencing factor that caused products obtained from enzyme reaction diverse. At a fixed time and pH value, we could simply adjust the concentration of hyaluronidase and get a series of HA fragments with different MW.
Then we used adipic acid dihydrazide (ADH) to obtain a series of HA-ADH conjugates with different chemical modification degrees. Carboxyl functional groups on HA were replaced by ADH under the catalysis of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). The modification degrees of HA changed with the reaction time and molar degrees of HA, ADH, and EDC.
Further, quantum dot conjugates HA-ADH-(QDot) with different characteristics (HA with different MW and modification degrees) were synthesized by conjugating HA-ADH with QDots. By ways of intravenous injection (IV) and oral administration, we studied the effects of MW and chemical modification degrees on the in vivo bio-distribution of HA using real-time imaging. The results showed that (i) HA with lower MW is metabolized rapidly after IV injection, while HA with higher MW could last longer time. The distributed amount of HA with lower MW in the chest and abdomen was more than HA with higher MW. [Lovvorn Iii, et al.] HA with lesser modification degrees showing the more specific distribution, accumulated in liver, and more rapid clearance after tail-vein injection; whereas HA with higher modification degrees, and its properties will be greatly affected, showing a more even tissue distribution in the body after IV injection.
On the other hand, the results of oral application showed: (i) HA with lower MW absorbed more rapidly after oral administration, while HA with higher MW demonstrated slower absorption and clearance. [Lovvorn Iii, et al.] The clearance of HA with higher modification degrees was slower than HA with lesser modification degrees. In the head, neck, and chest, HA with lesser modification degrees showed more distribution amount than higher one after oral ingestion. In addition, the amount of HA with higher modification degrees distributed to pelvis was more than lesser one.
It was concluded that the MW was the main factor that affected in vivo distribution of HA after IV injection, while the degree of chemical modification was the main factor that affected the bio-distribution of HA after oral administration. HA with suitable sizes and chemical modification degrees could be chosen for delivery of oral drugs with diverse characteristics. |
| 關聯: | 149頁 |
| 描述: | 目錄 I
附表目錄 V
附圖目錄 VI
中文摘要 XI
Abstract XIII
縮寫表 XV
第一章 緒論 1
第一節 研究背景介紹 1
一、玻尿酸Hyaluronic acid (HA) 1
（一）玻尿酸的基本特性 1
1. 玻尿酸的結構功能及其分佈 1
2. 玻尿酸的生理功能 6
3. 玻尿酸與玻尿酸受體的交互作用及其調控機轉 10
4. 玻尿酸的體內降解與代謝 13
（二）玻尿酸分子量的分析方法 16
（三）體外降解玻尿酸的方法 24
（四）修飾的玻尿酸衍生物 28
（五）玻尿酸的應用 37
（六）玻尿酸的劑型介紹 46
二、量子點Quantum dots（QDots） 51
（一）量子點的特性 51
（二）量子點的應用 52
（三）量子點與玻尿酸 54
第二節 研究動機與目的 57
第二章 實驗材料與方法 58
第一節 實驗材料 58
第二節 儀器設備 59
第三節 實驗方法 61
一、玻尿酸分析方法之開發與確立 61
（一）玻尿酸標準品溶液之配製 61
（二）利用分子篩滲透層析法進行玻尿酸分子量分析並建立玻尿酸分子量檢量線 62
二、建構體外玻尿酸酵素消化模式 63
（一）玻尿酸溶液之安定性 63
（二）酵素消化反應 64
三、玻尿酸之化學性修飾 65
（一）經ADH修飾之玻尿酸衍生物的製備及性質評估 65
四、玻尿酸於動物體內分佈即時顯像試驗 68
（一）量子點玻尿酸接合物之製備及性質評估 68
（二）動物試驗 70
1. 實驗動物 71
2. 試驗方法 71
3. 玻尿酸體內分佈評估 72
第三章 結果與討論 73
第一節 玻尿酸分析方法之開發與確立 73
一、利用分子篩滲透層析法進行玻尿酸分子量分析並建立玻尿酸分子量檢量線 73
第二節 建構體外玻尿酸酵素消化模式 76
一、玻尿酸溶液之安定性 77
二、酵素消化反應 79
第三節 玻尿酸之化學性修飾 88
一、經ADH修飾之玻尿酸衍生物的製備及性質評估 88
第四節 玻尿酸於動物體內分佈即時顯像試驗 102
一、量子點玻尿酸接合物之製備及性質評估 102
二、玻尿酸動物體內分佈評估 108
第四章 結論 135
參考文獻 137
Abdellaoui, K.S. and Malle, B.M. 2008. Composition with several hyaluronic acid fractions for cosmetic use. US Patent 2008/0003271 A1
Akima, K., Ito, H., Iwata, Y. et al. 1996. Evaluation of antitumor activities of hyaluronate binding antitumor drugs: Synthesis, characterization and antitumor activity. Journal of Drug Targeting 4: 1-8
Alaniz, L., Cabrera, P.V., Blanco G, G. et al. 2002. Interaction of CD44 with different forms of hyaluronic acid. Its role in adhesion and migration of tumor cells. Cell Communication and Adhesion 9: 117-130
Aruffo, A., Stamenkovic, I., Melnick, M. et al. 1990. CD44 is the principal cell surface receptor for hyaluronate. Cell 61: 1303-1313
Asari, A. and Miyauchi, S. 2000. Medical Application of hyaluronan. http://www.glycoforum.gr.jp/science/hyaluronan/HA13/HA13E.html
Astériou, T., Vincent, J.C., Tranchepain, F. et al. 2006. Inhibition of hyaluronan hydrolysis catalysed by hyaluronidase at high substrate concentration and low ionic strength. Matrix Biology 25: 166-174
Asteriou, T., Deschrevel, B., Delpech, B. et al. 2001. An improved assay for the N-acetyl-D-glucosamine reducing ends of polysaccharides in the presence of proteins. Analytical Biochemistry 293: 53-59
Auzenne, E., Ghosh, S.C., Khodadadian, M. et al. 2007. Hyaluronic acid-paclitaxel: Antitumor efficacy against CD44(+) human ovarian carcinoma xenografts. Neoplasia 9: 479-486
Bahary, W.S. and Jilani, M. 1993. Universal calibration assessment in aqueous gel permeation chromatography. Journal of Applied Polymer Science 48: 1531-1538
Baker, J.R. and Pritchard, D.G. 2000. Action pattern and substrate specificity of the hyaluronan lyase from group B streptococci. Biochemical Journal 348: 465-471
Balazs, E.A. and Band, P.A. 2008. Therapeutic Use of Hyaluronan-Based Products. In Carbohydrate Chemistry, Biology and Medical Applications. (Hari, G.G. et al., eds.) 311-332. Elsevier
Balazs, E.A. and Denlinger, J.L. 1993. Viscosupplementation: A new concept in the treatment of osteoarthritis. Journal of Rheumatology 20: 3-9
Balogh, L., Polyak, A., Mathe, D. et al. 2008. Absorption, uptake and tissue affinity of high-molecular-weight hyaluronan after oral administration in rats and dogs. Journal of Agricultural and Food Chemistry 56: 10582-10593
Banerji, S., Wright, A.J., Noble, M. et al. 2007. Structures of the Cd44-hyaluronan complex provide insight into a fundamental carbohydrate-protein interaction. Nature Structural and Molecular Biology 14: 234-239
Banzato, A., Rondina, M., Meléndez-Alafort, L. et al. 2009. Biodistribution imaging of a paclitaxel-hyaluronan bioconjugate. Nuclear Medicine and Biology 36: 525-533
Bertolini, G., Paleari, L., Catassi, A. et al. 2008. In vivo cancer imaging with semiconductor quantum dots. Current Pharmaceutical Analysis 4: 197-205
Bezáková, Z., Hermannová, M., Dřímalová, E. et al. 2008. Effect of microwave irradiation on the molecular and structural properties of hyaluronan. Carbohydrate Polymers 73: 640-646
Bhang, S.H., Won, N., Lee, T.J. et al. 2009. Hyaluronic acid-quantum dot conjugates for in vivo lymphatic vessel imaging. ACS Nano 3: 1389-1398
Biju, V., Mundayoor, S., Omkumar, R.V. et al. 2010. Bioconjugated quantum dots for cancer research: Present status, prospects and remaining issues. Biotechnology Advances 28: 199-213
Brown, M.B. and Jones, S.A. 2005. Hyaluronic acid: A unique topical vehicle for the localized delivery of drugs to the skin. Journal of the European Academy of Dermatology and Venereology 19: 308-318
Brown, T.J., Laurent, U.B.G. and Fraser, J.R.E. 1991. Turnover of hyaluronan in synovial joints: elimination of labelled hyaluronan from the knee joint of the rabbit. Experimental Physiology 76: 125-134
Bucci, L.R. and Turpin, A.A. 2004. Will the real hyaluronan please stand up? Journal of Applied Nutrition 54: 10-33
Bulpitt, P. and Aeschlimann, D. 1999. New strategy for chemical modification of hyaluronic acid: Preparation of functionalized derivatives and their use in the formation of novel biocompatible hydrogels. Journal of Biomedical Materials Research 47: 152-169
Cai, S., Xie, Y., Davies, N.M. et al. 2010. Pharmacokinetics and disposition of a localized lymphatic polymeric hyaluronan conjugate of cisplatin in rodents. Journal of Pharmaceutical Sciences 99: 2664-2671
Carreira, C.M., Nasser, S.M., Di Tomaso, E. et al. 2001. LYVE-1 is not restricted to the lymph vessels: Expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis. Cancer Research 61: 8079-8084
Chan, W.C.W., Maxwell, D.J., Gao, X. et al. 2002. Luminescent quantum dots for multiplexed biological detection and imaging. Current Opinion in Biotechnology 13: 40-46
Chan, W.C.W. and Nie, S. 1998. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281: 2016-2018
Christensen, B.E., Vold, I.M.N. and Vårum, K.M. 2008. Chain stiffness and extension of chitosans and periodate oxidised chitosans studied by size-exclusion chromatography combined with light scattering and viscosity detectors. Carbohydrate Polymers 74: 559-565
Cichy, J. and Puré, E. 2003. The liberation of CD44. Journal of Cell Biology 161: 839-843
Coradini, D., Pellizzaro, C., Abolafio, G. et al. 2004. Hyaluronic-acid butyric esters as promising antineoplastic agents in human lung carcinoma: A preclinical study. Investigational New Drugs 22: 207-217
Coradini, D., Zorzet, S., Rossin, R. et al. 2004. Inhibition of hepatocellular carcinomas in vitro and hepatic metastases in vivo in mice by the histone deacetylase inhibitor HA-But. Clinical Cancer Research 10: 4822-4830
Coward, R.T. 1998. Method of uaing hyaluronic acid for the detecting, location and diagnosis of tumors. US Patent 5772982
Cramer, J.A., Bailey, L.C., Bailey, C.A. et al. 1994. Kinetic and mechanistic studies with bovine testicular hyaluronidase. Biochimica et Biophysica Acta - General Subjects 1200: 315-321
Dabbousi, B.O., Rodriguez-Viejo, J., Mikulec, F.V. et al. 1997. (CdSe)ZnS core-shell quantum dots: Synthesis and characterization of a size series of highly luminescent nanocrystallites. Journal of Physical Chemistry B 101: 9463-9475
Deschrevel, B., Tranchepain, F. and Vincent, J.C. 2008. Chain-length dependence of the kinetics of the hyaluronan hydrolysis catalyzed by bovine testicular hyaluronidase. Matrix Biology 27: 475-486
Di Meo, C., Panza, L., Capitani, D. et al. 2007. Hyaluronan as carrier of carboranes for tumor targeting in boron neutron capture therapy. Biomacromolecules 8: 552-559
Eun, J.O., Ji, S.K. and Sei, K.H. 2007. A Novel Degradation Controlled Hyaluronic Acid Derivatives. Key Engineering Materials 342: 525-528
Eun, J.O., Kang, S.W., Kim, B.S. et al. 2008. Control of the molecular degradation of hyaluronic acid hydrogels for tissue augmentation. Journal of Biomedical Materials Research - Part A 86: 685-693
Eun, J.O., Kim, J.W., Kong, J.H. et al. 2008. Signal transduction of hyaluronic acid-peptide conjugate for formyl peptide receptor like 1 receptor. Bioconjugate Chemistry 19: 2401-2408
Ford, C. 2004. Chemistry celebrates a much-needed upgrade. http://www.morris.umn.edu/academic/science/news/chem2.html
Fraser, J.R.E., Laurent, T.C. and Laurent, U.B.G. 1997. Hyaluronan: Its nature, distribution, functions and turnover. Journal of Internal Medicine 242: 27-33
Fraser, J.R.E., Laurent, T.C., Pertoft, H. et al. 1981. Plasma clearance, tissue distribution and metabolism of hyaluronic acid injected intravenously in the rabbit. Biochemical Journal 200: 415-424
Gao, X., Cui, Y., Levenson, R.M. et al. 2004. In vivo cancer targeting and imaging with semiconductor quantum dots. Nature Biotechnology 22: 969-976
Gares, S.L., Giannakopoulos, N., MacNeil, D. et al. 1998. During human thymic development, β1 integrins regulate adhesion, motility, and the outcome of RHAMM/hyaluronan engagement. Journal of Leukocyte Biology 64: 781-790
Genasetti, A., Vigetti, D., Viola, M. et al. 2008. Hyaluronan and human endothelial cell behavior. Connective tissue research 49: 120-123
Ghatak, S., Misra, S. and Toole, B.P. 2005. Hyaluronan constitutively regulates ErbB2 phosphorylation and signaling complex formation in carcinoma cells. Journal of Biological Chemistry 280: 8875-8883
Ghosh, P. and Guidolin, D. 2002. Potential mechanism of action of intra-articular hyaluronan therapy in osteoarthritis: Are the effects molecular weight dependent? Seminars in Arthritis and Rheumatism 32: 10-37
Gianolio, D.A., Philbrook, M., Avila, L.Z. et al. 2005. Synthesis and evaluation of hydrolyzable hyaluronan-tethered bupivacaine delivery systems. Bioconjugate Chemistry 16: 1512-1518
Gianolio, D.A., Philbrook, M., Avila, L.Z. et al. 2008. Hyaluronan-tethered opioid depots: Synthetic strategies and release kinetics in vitro and in vivo. Bioconjugate Chemistry 19: 1767-1774
Goldberg, R.L. and Toole, B.P. 1987. Hyaluronate inhibition of cell proliferation. Arthritis and Rheumatism 30: 769-778
Green, M. and O'Brien, P. 1999. Recent advances in the preparation of semiconductors as isolated nanometric particles: New routes to quantum dots. Chemical Communications 22: 2235-2241
Grubisic, Z., Rempp, P. and Benoit, H. 1967. A universal calibration for gel permeation chromatography. Journal of Polymer Science Part B: Polymer Letters 5: 753-759
Guo, X., Condra, M., Kimura, K. et al. 2003. Determination of molecular weight of heparin by size exclusion chromatography with universal calibration. Analytical Biochemistry 312: 33-39
Hahn, S.K., Kim, J.S. and Shimobouji, T. 2007. Injectable hyaluronic acid microhydrogels for controlled release formulation of erythropoietin. Journal of Biomedical Materials Research - Part A 80: 916-924
Hahn, S.K., Kim, S.J., Kim, M.J. et al. 2004. Characterization and in vivo study of sustained-release formulation of human growth hormone using sodium hyaluronate. Pharmaceutical Research 21: 1374-1381
Hahn, S.K., Park, J.K., Tomimatsu, T. et al. 2007. Synthesis and degradation test of hyaluronic acid hydrogels. International Journal of Biological Macromolecules 40: 374-380
Hascall, V.C. and Laurent, T.C. 1997. Hyaluronan:structure and physical properties. http://www.glycoforum.gr.jp/science/hyaluronan/HA01/HA01E.html
Hiemstra, C., Van Der Aa, L.J., Zhong, Z. et al. 2007. Novel in situ forming, degradable dextran hydrogels by michael addition chemistry: Synthesis, rheology, and degradation. Macromolecules 40: 1165-1173
Hofinger, E.S.A., Bernhardt, G. and Buschauer, A. 2007. Kinetics of Hyal-1 and PH-20 hyaluronidases: Comparison of minimal substrates and analysis of the transglycosylation reaction. Glycobiology 17: 963-971
Hofinger, E.S.A., Hoechstetter, J., Oettl, M. et al. 2008. Isoenzyme-specific differences in the degradation of hyaluronic acid by mammalian-type hyaluronidases. Glycoconjugate Journal 25: 101-109
Hokputsa, S., Jumel, K., Alexander, C. et al. 2003. A comparison of molecular mass determination of hyaluronic acid using SEC/MALLS and sedimentation equilibrium. European Biophysics Journal 32: 450-456
Homma, A., Sato, H., Okamachi, A. et al. 2009. Novel hyaluronic acid-methotrexate conjugates for osteoarthritis treatment. Bioorganic and Medicinal Chemistry 17: 4647-4656
Huang, S.L., Ling, P.X. and Zhang, T.M. 2007. Oral absorption of hyaluronic acid and phospholipids complexes in rats. World Journal of Gastroenterology 13: 945-949
Hyung, W., Ko, H., Park, J. et al. 2008. Novel hyaluronic acid (HA) coated drug carriers (HCDCs) for human breast cancer treatment. Biotechnology and Bioengineering 99: 442-454
Jackson, D.G. 2003. The lymphatics revisited: New perspectives from the hyaluronan receptor LYVE-1. Trends in Cardiovascular Medicine 13: 1-7
Jackson, D.G. 2004. The lymphatic endothelial hyaluronan receptor LYVE-1. http://www.glycoforum.gr.jp/science/hyaluronan/HA28/HA28E.html
Jamieson, T., Bakhshi, R., Petrova, D. et al. 2007. Biological applications of quantum dots. Biomaterials 28: 4717-4732
Jederström, G., Andersson, A., Gråsjö, J. et al. 2004. Formulating insulin for oral administration: Preparation of hyaluronan-insulin complex. Pharmaceutical Research 21: 2040-2047
Jederström, G., Gråsjö, J., Nordin, A. et al. 2005. Blood glucose-lowering activity of a hyaluronan-insulin complex after oral administration to rats with diabetes. Diabetes Technology and Therapeutics 7: 948-957
Jedrzejas, M.J. 2000. Structural and functional comparison of polysaccharide-degrading enzymes. Critical Reviews in Biochemistry and Molecular Biology 35: 221-251
Jiang, G., Park, K., Kim, J. et al. 2009. Target specific intracellular delivery of siRNA/PEI-HA complex by receptor mediated endocytosis. Molecular Pharmaceutics 6: 727-737
Jiang, W., Papa, E., Fischer, H. et al. 2004. Semiconductor quantum dots as contrast agents for whole animal imaging. Trends in Biotechnology 22: 607-609
Kim, A., Checkla, D.M., Dehazya, P. et al. 2003. Characterization of DNA-hyaluronan matrix for sustained gene transfer. Journal of Controlled Release 90: 81-95
Kim, J., Kim, K.S., Jiang, G. et al. 2008. In vivo real-time bioimaging of hyaluronic acid derivatives using quantum dots. Biopolymers 89: 1144-1153
Kim, S., Lim, Y.T., Soltesz, E.G. et al. 2004. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nature Biotechnology 22: 93-97
Kobayashi, H., Suzuki, M., Kanayama, N. et al. 2002. CD44 stimulation by fragmented hyaluronic acid induces upregulation of urokinase-type plasminogen activator and its receptor and subsequently facilitates invasion of human chondrosarcoma cells. International Journal of Cancer 102: 379-389
Kojima, M., Takahashi, K. and Nakamura, K. 2001. Cationic dye-sensitized degradation of sodium hyaluronate through photoinduced electron transfer in the upper excited state. Photochemistry and Photobiology 74: 369-377
Kong, J.H., Oh, E.J., Chae, S.Y. et al. 2010. Long acting hyaluronate - exendin 4 conjugate for the treatment of type 2 diabetes. Biomaterials 31: 4121-4128
Kooy, F.K., Ma, M., Beeftink, H.H. et al. 2009. Quantification and characterization of enzymatically produced hyaluronan with fluorophore-assisted carbohydrate electrophoresis. Analytical Biochemistry 384: 329-336
Kostanski, L.K., Keller, D.M. and Hamielec, A.E. 2004. Size-exclusion chromatography - A review of calibration methodologies. Journal of Biochemical and Biophysical Methods 58: 159-186
Kreil, G. 1995. Hyaluronidases - A group of neglected enzymes. Protein Science 4: 1666-1669
Laurent, T.C., Dahl, I.M., Dahl, L.B. et al. 1986. The catabolic fate of hyaluronic acid. Connective tissue research 15: 33-41
Laurent, T.C. and Fraser, J.R.E. 1992. Hyaluronan. FASEB Journal 6: 2397-2404
Leach, J.B., Bivens, K.A., Collins, C.N. et al. 2004. Development of photocrosslinkable hyaluronic acid-polyethylene glycol-peptide composite hydrogels for soft tissue engineering. Journal of Biomedical Materials Research - Part A 70: 74-82
Lee, F., Chung, J.E. and Kurisawa, M. 2008. An injectable enzymatically crosslinked hyaluronic acid-tyramine hydrogel system with independent tuning of mechanical strength and gelation rate. Soft Matter 4: 880-887
Lee, F., Chung, J.E. and Kurisawa, M. 2009. An injectable hyaluronic acid-tyramine hydrogel system for protein delivery. Journal of Controlled Release 134: 186-193
Lee, H., Lee, K., Kim, I.K. et al. 2008. Synthesis, characterization, and in vivo diagnostic applications of hyaluronic acid immobilized gold nanoprobes. Biomaterials 29: 4709-4718
Lee, H., Lee, K. and Tae, G.P. 2008. Hyaluronic acid-paclitaxel conjugate micelles: Synthesis, characterization, and antitumor activity. Bioconjugate Chemistry 19: 1319-1325
Lee, H., Mok, H., Lee, S. et al. 2007. Target-specific intracellular delivery of siRNA using degradable hyaluronic acid nanogels. Journal of Controlled Release 119: 245-252
Lee, Y., Lee, H., Kim, Y.B. et al. 2008. Bioinspired surface immobilization of hyaluronic acid on monodisperse magnetite nanocrystals for targeted cancer imaging. Advanced Materials 20: 4154-4157
Leneau, H. 2003. Ingestion of hyaluronic acid for improved joint function and health. US Patent 6607745
Lim, S.T., Forbes, B., Berry, D.J. et al. 2001. In vivo evaluation of novel hyaluronan/chitosan microparticulate delivery systems for the nasal delivery of gentamicin in rabbits. International Journal of Pharmaceutics 231: 73-82
Lin, Z., Cui, S., Zhang, H. et al. 2003. Studies on quantum dots synthesized in aqueous solution for biological labeling via electrostatic interaction. Analytical Biochemistry 319: 239-243
Liu, L.S., Ng, C.K., Thompson, A.Y. et al. 2002. Hyaluronate-heparin conjugate gels for the delivery of basic fibroblast growth factor (FGF-2). Journal of Biomedical Materials Research 62: 128-135
Liu, N., Shao, L., Xu, X. et al. 2002. Hyaluronan metabolism in rat tail skin following blockage of the lymphatic circulation. Lymphology 35: 15-22
Liu, T., Liu, B., Zhang, H. et al. 2005. The fluorescence bioassay platforms on quantum dots nanoparticles. Journal of Fluorescence 15: 729-733
Lovvorn Iii, H.N., Cass, D.L., Sylvester, K.G. et al. 1998. Hyaluronan receptor expression increases in fetal excisional skin wounds and correlates with fibroplasia. Journal of Pediatric Surgery 33: 1062-1070
Luo, Y., Bernshaw, N.J., Lu, Z.R. et al. 2002. Targeted delivery of doxorubicin by HPMA copolymer-hyaluronan bioconjugates. Pharmaceutical Research 19: 396-402
Luo, Y. and Prestwich, G.D. 1999. Synthesis and selective cytotoxicity of a hyaluronic acid-antitumor bioconjugate. Bioconjugate Chemistry 10: 755-763
Luo, Y., Ziebell, M.R. and Prestwich, G.D. 2000. A hyaluronic acid - Taxol antitumor bioconjugate targeted to cancer cells. Biomacromolecules 1: 208-218
Madere, S.P. 2007. Composition of orally administered nutritional supplements to repair articular cartilage. US Patent 7214666
Menzel, E.J. and Farr, C. 1998. Hyaluronidase and its substrate hyaluronan: Biochemistry, biological activities and therapeutic uses. Cancer Letters 131: 3-11
Michler, P., Kiraz, A., Becher, C. et al. 2000. A quantum dot single-photon turnstile device. Science 290: 2282-2285
Misra, S., Ghatak, S. and Toole, B.P. 2005. Regulation of MDR1 expression and drug resistance by a positive feedback loop involving hyaluronan, phosphoinositide 3-kinase, and ErbB2. Journal of Biological Chemistry 280: 20310-20315
Misra, S., Ghatak, S., Zoltan-Jones, A. et al. 2003. Regulation of multidrug resistance in cancer cells by hyaluronan. Journal of Biological Chemistry 278: 25285-25288
Mochizuki, S., Kano, A., Yamayoshi, A. et al. 2006. Hyaluronan conjugation of antigenic protein to modify immunogenic information. Science and Technology of Advanced Materials 7: 685-691
Mok, H., Ji, W.P. and Tae, G.P. 2007. Antisense oligodeoxynucleotide-conjugated hyaluronic acid/protamine nanocomplexes for intracellular gene inhibition. Bioconjugate Chemistry 18: 1483-1489
Morimoto, K., Metsugi, K., Katsumata, H. et al. 2001. Effects of low-viscosity sodium hyaluronate preparation on the pulmonary absorption of rh-insulin in rats. Drug Development and Industrial Pharmacy 27: 365-371
Motokawa, K., Hahn, S.K., Nakamura, T. et al. 2006. Selectively crosslinked hyaluronic acid hydrogels for sustained release formulation of erythropoietin. Journal of Biomedical Materials Research - Part A 78: 459-465
Muckenschnabel, I., Bernhardt, G., Spruss, T. et al. 1998. Quantitation of hyaluronidases by the Morgan-Elson reaction: Comparison of the enzyme activities in the plasma of tumor patients and healthy volunteers. Cancer Letters 131: 13-20
Murai, T. and Kawashima, H. 2008. A simple assay for hyaluronidase activity using fluorescence polarization. Biochemical and Biophysical Research Communications 376: 620-624
Noble, P.W. 2002. Hyaluronan and its catabolic products in tissue injury and repair. Matrix Biology 21: 25-29
Oh, E.J., Park, K., Choi, J.S. et al. 2009. Synthesis, characterization, and preliminary assessment of anti-Flt1 peptide-hyaluronate conjugate for the treatment of corneal neovascularization. Biomaterials 30: 6026-6034
Oh, E.J., Park, K., Kim, K.S. et al. 2010. Target specific and long-acting delivery of protein, peptide, and nucleotide therapeutics using hyaluronic acid derivatives. Journal of Controlled Release 141: 2-12
Ossipov, D.A. 2010. Nanostructured hyaluronic acid-based materials for active delivery to cancer. Expert Opinion on Drug Delivery 7: 681-703
Park, J.K., Yeom, J., Oh, E.J. et al. 2009. Guided bone regeneration by poly(lactic-co-glycolic acid) grafted hyaluronic acid bi-layer films for periodontal barrier applications. Acta Biomaterialia 5: 3394-3403
Pierce, S.W. 2005. Chondroprotective/restorative compositions and methods of use thereof. US Patent 6924273
Pilarski, L.M., Masellis-Smith, A., Belch, A.R. et al. 1994. RHAMM, a receptor for Hyaluronan-Mediated Motility, on normal human lymphocytes, thymocytes and malignant B cells: A mediator in B cell malignancy? Leukemia and Lymphoma 14: 363-374
Pinaud, F., Michalet, X., Bentolila, L.A. et al. 2006. Advances in fluorescence imaging with quantum dot bio-probes. Biomaterials 27: 1679-1687
Plattt, V.M. and Szoka Jr, F.C. 2008. Anticancer therapeutics: Targeting macromolecules and nanocarriers to hyaluronan or CD44, a hyaluronan receptor. Molecular Pharmaceutics 5: 474-486
Ponta, H., Sherman, L. and Herrlich, P.A. 2003. CD44: From adhesion molecules to signalling regulators. Nature Reviews Molecular Cell Biology 4: 33-45
Pouyani, T., Harbison, G.S. and Prestwich, G.D. 1994. Novel hydrogels of hyaluronic acid: Synthesis, surface morphology, and solid-state NMR. Journal of the American Chemical Society 116: 7515-7522
Pouyani, T. and Prestwich, G.D. 1994. Functionalized derivatives of hyaluronic acid oligosaccharides: Drug carriers and novel biomaterials. Bioconjugate Chemistry 5: 339-347
Prestwich, G.D. 2001. Biomaterials from chemically-modified hyaluronan. http://www.glycoforum.gr.jp/science/hyaluronan/HA18/HA18E.html
Prevo, R., Banerji, S., Ferguson, D.J.P. et al. 2001. Mouse LYVE-1 Is an Endocytic Receptor for Hyaluronan in Lymphatic Endothelium. Journal of Biological Chemistry 276: 19420-19430
Rochira, M., Miglietta, M.R., Richardson, J.L. et al. 1996. Novel vaginal delivery systems for calcitonin. II. Preparation and characterization of HYAFF® microspheres containing calcitonin. International Journal of Pharmaceutics 144: 19-26
Rosato, A., Banzato, A., De Luca, G. et al. 2006. HYTAD1-p20: A new paclitaxel-hyaluronic acid hydrosoluble bioconjugate for treatment of superficial bladder cancer{star, open}. Urologic Oncology: Seminars and Original Investigations 24: 207-215
Rossler, A. and Hinghofer-Szalkay, H. 2003. Hyaluronan fragments: An information-carrying system? Hormone and Metabolic Research 35: 67-68
Roth, M., Papakonstantinou, E. and Karakiulakis, G. 2008. Biological Function of Glycosaminoglycans. In Carbohydrate Chemistry, Biology and Medical Applications. (Hari, G.G. et al., eds.) 209-226. Elsevier
Saitoh, H., Takagaki, K., Majima, M. et al. 1995. Enzymic reconstruction of glycosaminoglycan oligosaccharide chains using the transglycosylation reaction of bovine testicular hyaluronidase. Journal of Biological Chemistry 270: 3741-3747
Sakurai, K., Andoh, M., Yamada, M. et al. 1997. Suppression of ischemic edema in mice by manganese-hyaluronate conjugate. Japanese Journal of Pharmacology 74: 117-120
Sakurai, K., Miyazaki, K., Kodera, Y. et al. 1997. Anti-inflammatory activity of superoxide dismutase conjugated with sodium hyaluronate. Glycoconjugate Journal 14: 723-728
Sandri, G., Bonferoni, M.C., Chetoni, P. et al. 2006. Ophthalmic delivery systems based on drug-polymer-polymer ionic ternary interaction: In vitro and in vivo characterization. European Journal of Pharmaceutics and Biopharmaceutics 62: 59-69
Schledzewski, K., Falkowski, M., Moldenhauer, G. et al. 2006. Lympathic endothelium-specific hyaluronan receptor LYVE-1 is expressed by stabilin-1+, F4/80+, CD11b+ macropahages in malignant tumours and wound healing tissue in vivo and in bone marrow cultures in vitro: Implications for the assessment of lymphangiogenesis. Journal of Pathology 209: 67-77
Scott, J.E., Cummings, C., Brass, A. et al. 1991. Secondary and tertiary structures of hyaluronan in aqueous solution, investigated by rotary shadowing-electron microscopy and computer simulation. Hyaluronan is a very efficient network-forming polymer. Biochemical Journal 274: 699-705
Scott, J.E. and Heatley, F. 2002. Biological properties of hyaluronan in aqueous solution are controlled and sequestered by reversible tertiary structures, defined by NMR spectroscopy. Biomacromolecules 3: 547-553
Segura, T., Anderson, B.C., Chung, P.H. et al. 2005. Crosslinked hyaluronic acid hydrogels: A strategy to functionalize and pattern. Biomaterials 26: 359-371
Serban, M.A. and Prestwich, G.D. 2007. Synthesis of hyaluronan haloacetates and biology of novel cross-linker-free synthetic extracellular matrix hydrogels. Biomacromolecules 8: 2821-2828
Sousa, A.S., Guimarães, A.P., Goncalves, C.V. et al. 2009. Purification and characterization of microbial hyaluronic acid by solvent precipitation and size-exclusion chromatography. Separation Science and Technology 44: 906-923
Stern, R. 2004. Hyaluronan catabolism: A new metabolic pathway. European Journal of Cell Biology 83: 317-325
Stern, R. 2004. Update on the mammalian hyaluronidases.
Stern, R., Asari, A.A. and Sugahara, K.N. 2006. Hyaluronan fragments: An information-rich system. European Journal of Cell Biology 85: 699-715
Stern, R., Kogan, G., Jedrzejas, M.J. et al. 2007. The many ways to cleave hyaluronan. Biotechnology Advances 25: 537-557
Strand, V., Conaghan, P.G., Lohmander, L.S. et al. 2006. An integrated analysis of five double-blind, randomized controlled trials evaluating the safety and efficacy of a hyaluronan product for intra-articular injection in osteoarthritis of the knee. Osteoarthritis and Cartilage 14: 859-866
Sun, J.K., Sei, K.H., Myung, J.K. et al. 2005. Development of a novel sustained release formulation of recombinant human growth hormone using sodium hyaluronate microparticles. Journal of Controlled Release 104: 323-335
Surendrakumar, K., Martyn, G.P., Hodgers, E.C.M. et al. 2003. Sustained release of insulin from sodium hyaluronate based dry powder formulations after pulmonary delivery to beagle dogs. Journal of Controlled Release 91: 385-394
Takagaki, K., Nakamura, T., Izumi, J. et al. 1994. Characterization of hydrolysis and transglycosylation by testicular hyaluronidase using ion-spray mass spectrometry. Biochemistry 33: 6503-6507
Takahashi, T., Ikegami-Kawai, M., Okuda, R. et al. 2003. A fluorimetric Morgan-Elson assay method for hyaluronidase activity. Analytical Biochemistry 322: 257-263
Takei, Y., Maruyama, A., Ferdous, A. et al. 2004. Targeted gene delivery to sinusoidal endothelial cells: DNA nanoassociate bearing hyaluronan-glycocalyx. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18: 699-701
Tranchepain, F., Deschrevel, B., Courel, M.N. et al. 2006. A complete set of hyaluronan fragments obtained from hydrolysis catalyzed by hyaluronidase: Application to studies of hyaluronan mass distribution by simple HPLC devices. Analytical Biochemistry 348: 232-242
Turley, E.A. and Asculai, S.S. 2003. Oral administration of effective amounts of forms of hyaluronic acid. US Patent 6537978
Turley, E.A., Noble, P.W. and Bourguignon, L.Y.W. 2002. Signaling properties of hyaluronan receptors. Journal of Biological Chemistry 277: 4589-4592
Udell, R.G. and Naguib, Y.M.A. 2004. Hyaluronic acid in soft gel form. US Patent 6806259
Volpi, N. 2007. On-line HPLC/ESI-MS separation and characterization of hyaluronan oligosaccharides from 2-mers to 40-mers. Analytical Chemistry 79: 6390-6397
Volpi, N., Zhang, Z. and Linhardt, R.J. 2008. Mass spectrometry for the characterization of unsulfated chondroitin oligosaccharides from 2-mers to 16-mers. Comparison with hyaluronic acid oligomers. Rapid Communications in Mass Spectrometry 22: 3526-3530
Waters, J. and Leiske, D. 2005. Characterization of hyaluronic acid with on-line differential viscometry, multiangle light scattering, and differential refractometry. LC-GC North America 23: 302-310
Weigel, P.H. and Yik, J.H.N. 2002. Glycans as endocytosis signals: The cases of the asialoglycoprotein and hyaluronan/chondroitin sulfate receptors. Biochimica et Biophysica Acta - General Subjects 1572: 341-363
Wobig, M., Bach, G., Beks, P. et al. 1999. The role of elastoviscosity in the efficacy of viscosupplementation for osteoarthritis of the knee: A comparison of hylan G-F 20 and a lower- molecular-weight hyaluronan. Clinical Therapeutics 21: 1549-1562
Woo, J.S., Piao, M.G., Li, D.X. et al. 2007. Development of cyclosporin A-loaded hyaluronic microsphere with enhanced oral bioavailability. International Journal of Pharmaceutics 345: 134-141
Xin, D., Wang, Y. and Xiang, J. 2010. The use of amino acid linkers in the conjugation of paclitaxel with hyaluronic acid as drug delivery system: Synthesis, self-assembled property, drug release, and in vitro efficiency. Pharmaceutical Research 27: 380-389
Xue, F.L., Chen, J.Y., Guo, J. et al. 2007. Enhancement of intracellular delivery of CdTe quantum dots (QDs) to living cells by tat conjugation. Journal of Fluorescence 17: 149-154
Yannariello-Brown, J., Frost, S.J. and Weigel, P.H. 1992. Identification of the Ca2+-independent endocytic hyaluronan receptor in rat liver sinusoidal endothelial cells using a photoaffinity cross-linking reagent. Journal of Biological Chemistry 267: 20451-20456
Yau, W.W., Kirkland, J.J. and Bly, D.D. 1979. In Modern Size Exclusion Chromatography. (Snyder, L. and Kirkland, J.J. eds.) John Wiley & Sons, Inc.
Yenice, I., Mocan, M.C., Palaska, E. et al. 2008. Hyaluronic acid coated poly-ε-caprolactone nanospheres deliver high concentrations of cyclosporine A into the cornea. Experimental Eye Research 87: 162-167
Yeo, Y., Highley, C.B., Bellas, E. et al. 2006. In situ cross-linkable hyaluronic acid hydrogels prevent post-operative abdominal adhesions in a rabbit model. Biomaterials 27: 4698-4705
Yuan, Z., Kardynal, B.E., Stevenson, R.M. et al. 2002. Electrically driven single-photon source. Science 295: 102-105
Yun, Y.H., Goetz, D.J., Yellen, P. et al. 2004. Hyaluronan microspheres for sustained gene delivery and site-specific targeting. Biomaterials 25: 147-157
Zhong, S.P., Campoccia, D., Doherty, P.J. et al. 1994. Biodegradation of hyaluronic acid derivatives by hyaluronidase. Biomaterials 15: 359-365
Zhou, B., Weigel, J.A., Fauss, L. et al. 2000. Identification of the hyaluronan receptor for endocytosis (HARE). Journal of Biological Chemistry 275: 37733-37741
Zhou, B., Weigel, J.A., Saxena, A. et al. 2002. Molecular cloning and functional expression of the rat 175-kDA hyaluronan receptor for endocytosis. Molecular Biology of the Cell 13: 2853-2868 |
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