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指導老師 ： 謝慶東 學生： 鄞伯勳 2013.12.27

指導老師 ： 謝慶東 學生： 鄞伯勳 2013.12.27. 摘要 前言 實驗材料 實驗方法 結果與討論 結論 參考文獻. 目錄.

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指導老師 ： 謝慶東 學生： 鄞伯勳 2013.12.27

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  1. 指導老師：謝慶東 學生：鄞伯勳 2013.12.27

  2. 摘要 前言 實驗材料 實驗方法 結果與討論 結論 參考文獻 目錄

  3. 為了延長藥物在角膜前停留時間，因此提高了的眼部藥物的生物利用度，Plu-F127接枝聚丙烯酸(PAA)的共聚物進行了研究，如原位成膠基質為眼科藥物遞送系統。流變學特性和體外藥物的Pluronic -G- PAA的釋放共聚物凝膠進行研究的流變圖和體外藥物釋放研究顯示，該藥物的釋放速率與PAA/Plurnicmole比和共聚物溶液的濃度增加而下降，但藥物濃度對藥物釋放無明顯影響。從這些共聚物凝膠的藥物釋放率主要取決於凝膠降解。 摘要(1)

  4. 跟市面上眼藥相比較，在體內試驗說明該藥原位凝膠停留時間和總量在兔結膜囊裡增加了5.0和2.6倍的。在正常體溫下能夠減少在角膜上的耗損，而且可以在眼角膜上停留較長時間兩點得知，該共聚物凝膠具有生物黏附性。跟市面上眼藥相比較，在體內試驗說明該藥原位凝膠停留時間和總量在兔結膜囊裡增加了5.0和2.6倍的。在正常體溫下能夠減少在角膜上的耗損，而且可以在眼角膜上停留較長時間兩點得知，該共聚物凝膠具有生物黏附性。 這些體內實驗結果，隨著流變學特性和體外藥物釋放研究中，證明了在含有原位凝膠Pluronic-G -PAA共聚物可顯著延長藥物停留時間，從而提高生物利用度。的Pluronic -G- PAA共聚物是儀具有發展性的原位成膠載體眼科藥物傳遞系統。 摘要(2)

  5. 此實驗為了使眼藥在眼角結膜的滯留時間延長，採用Pluronic F127-g-PAA為原位成膠載體的眼藥輸送系統，以流變性質和體外釋放來證實Pluronic F127-g-PAA在生物體上的生物相容性。 前言

  6. Pluronic F127 Acrylic acid (AAc) 2,2’-azobisisobutyronitrile (AIBN) 起始劑 Gatifloxacin(GTX) 實驗材料

  7. 實驗方法 AAc + 去離子水 + 2,2’-azobisisobutyronitrile(起始劑) 配製成PAA溶液 PAA溶液+ Pluronic F127溶液混和 Plu 18% - g – PAA(4.0%、6.0%、8.0%)

  8. 結果與討論

  9. FTIR A =1109.9c-o-c B=1715 c=o FTIR spectra of Pluronic F127 (a), PAA (b) and Pluronic-g-PAA copolymer (c) 由此得知此物理混合非常良好，才能夠擁有一樣的官能基

  10. 聚分散皆小於1.2

  11. Rheological properties Temperature-dependent elasticity modulus (G’, ● ) and viscosity modulus (G’’, ○) of 4.0% (w/v) aqueous solution of the Pluronic-g-PAA copolymer. (b)Differential curve of elasticity modulus of the Pluronic-g-PAA copolymer (copolymer2) (a)the Pluronic-g-PAA 由溶液變膠態時 G’<G’’ G’>G’’ G’=G’’ (b)彈性模數對溫度的微分曲線 35.1度為成膠溫度

  12. Temperature-dependent elasticity modulus (G’) (a) and differential curve (b) of 4.0% (w/v) aqueous solutions of copolymer3 (●), copolymer2 (□), copolymer1(▲), and physical mixture (the molar ratio of PAA/Pluronic = 1) (○). (a)各濃度的彈性模數隨著溫度上升而上升

  13. 黏性膜數也隨溫度上升而上升 在相同溫度下黏性膜數隨莫耳比上升

  14. Temperature-dependent elasticity modulus (G’) (a) and differential curve (b) of 8.0% (□), 6.0% (●) and 4.0% (○) (w/v) aqueous solutions of copolymer2.

  15. Rheological properties of aqueous solutions of copolymer (●) and physical mixture (▲) as a function of frequency at different temperature. Modulus(elasticity modulus, G’, filled symbols; viscosity modulus, G’’, unfilled symbols), 25◦C. (b) Loss angle, 25 ◦C. (c) Modulus (elasticity modulus, G’, filled symbols;viscosity modulus, G’’, unfilled symbols), 35◦C. (d) Loss angle, 35 ◦C.

  16. In vitro release studies Gel dissolution (■) and drug release (●) profiles of 0.2% gatifloxacinin situ gels containing 4.0% (w/v) copolymer3. (b) Plot of percent of drug releasedvs. percent of gel dissolved.

  17. Effect of various parameters on drug release. Flow rate of the release medium: 2.00mLmin−1 (■), 1.00mLmin−1 (○) and 0.50mLmin−1 (●). (b)Acrylic acid/Pluronic molar ratio: 1.07 (■), 1.79 (○) and 3.12 (●). (c) Copolymer solution concentration: 4.0% (■), 6.0% (○) and 8.0% (●) (w/v). (d) Entrappeddrug concentration: 2.0 mgmL−1 (■), 1.0 mgmL−1 (○) and 0.5 mgmL−1 (●).

  18. In vivo resident experiments The level of gatifloxacin in rabbit’s conjunctiveal sac after instillation of 0.2% gatifloxacin eye drop (■) and as in situ gel containing 4.0% (w/v) copolymer3 (●).

  19. 結論 流變性質在測試Pluronic-g-PAA的生物黏附性較適合溫度響應型的凝 膠，其中以濃度Plu 18% - g – PAA4.0%最為合適。 藥物動力學零級釋放觀察，以各種實驗的因素(藥物濃度、共聚合 物濃度、莫耳比、釋放流量)，這種共聚物凝膠的藥物釋放主要取決 於凝膠上的溶解。 在體內實驗的結果，以及流變和在體外藥物釋放研究，可證明在原位成膠中的Pluronic-g-PAA共聚物可顯著延長角膜前的滯留時間，並可能進一步改善眼部藥物的生物利用度。

  20. Bhardwaj, R., Blanchard, J., 1996. Controlled-release delivery system for the -MSH analog melanotan-I using poloxamer 407. J. Pharm. Sci. 85, 915–919. Bochot, A., Fattal, E., Gulik, A., Couarraze, G., Couvreur, P., 1998. Liposomesdispersed within a thermosensitive gel: a newdosage form for ocular deliveryof oligonucleotides. Pharm. Res. 15, 1364–1369. Bromberg, L., 1998a. Novel family of thermo-gelling materials via C–C bondingbetween poly(acrylic acid) and poly(ethylene oxide)-b-poly(propyleneoxide)-b-poly(ethylene oxide). J. Phys. Chem. B 102, 1956–1963. Bromberg, L., 1998b. Properties of aqueous solutions and gels ofpoly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide)-gpoly(acrylic acid). J. Phys. Chem. B 102, 10736–10744. Bromberg, L., 2001a. Synthesis and self-assembly of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide)-g-poly(acrylic acid). Ind.Eng. Chem. Res. 40, 2437–2444. 參考文獻

  21. Bromberg, L., 2001b. Interactions among proteins and hydrophobically modifiedpolyelectrolytes. J. Pharm. Pharmacol. 53, 541–547. Bromberg, L., 2001c. Enhanced nasal retention of hydrophobically modified polyelectrolytes. J. Pharm. Pharmacol. 53, 109–114. Bromberg, L., Ron, E.S., 1998. Protein and peptide release from temperatureresponsivegels and thermogelling polymer matrices. Adv. Drug Deliv. Rev.31, 197–221. Bromberg, L., Temchenko, M., Alakhov, V., Hatton, T.A., 2004a. Bioadhesiveproperties and rheology of polyether-modified poly(acrylic acid) hydrogels.Int. J. Pharm. 282, 45–60. Bromberg, L., Temchenko, M., Moesser, G.D., Hatton, T.A., 2004b. Thermodynamicsof temperature-sensitive polyether-modified poly(acrylic acid)microgels. Langmuir 20, 5683–5692. 參考文獻

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