跳到主要內容

臺灣博碩士論文加值系統

(18.97.14.86) 您好!臺灣時間:2025/02/12 22:29
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:賴翊慈
研究生(外文):Yi-Cih Lai
論文名稱:發展長效型抗皺磷酸鈣輔助微米皮下填充物
論文名稱(外文):Development of Calcium Phosphate Assisted Micro Dermal Filler with Antiwrinkles Longevity
指導教授:賴秉杉
口試委員:廖明淵林華洋
口試日期:2017-07-06
學位類別:碩士
校院名稱:國立中興大學
系所名稱:化學系所
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:英文
論文頁數:57
中文關鍵詞:玻尿酸磷酸鈣微球皮下注射填充物膠原蛋白
外文關鍵詞:Hyaluronic acidCalcium phosphateMicroparticlesDermal fillersCollagen
相關次數:
  • 被引用被引用:0
  • 點閱點閱:286
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
近年來,皮下注射填充物在醫學美容市場中迅速發展。其中,玻尿酸的生物相容性、生物可降解性以及高吸水性,使之成為皮下填充物之主要材料。然而,未經交聯之玻尿酸在生理環境中容易被酵素分解,進而被人體代謝,降低其在皮膚組織之耐受性,因而限制玻尿酸作為皮下填充物之應用。為了解決上述問題,該研究開發出具有磷酸鈣修飾的交聯玻尿酸微球作為長效型皮下注射填充物。
本研究中發展之玻尿酸微球粒徑大於20微米,因此可以降低注射後直接被巨噬細胞吞噬的可能性。另外,相較於具有銳角之粒子,球狀粒子也可以降低注射後所引發的異物反應。在玻尿酸酵素降解實驗結果中,磷酸鈣修飾的策略可以有效減緩玻尿酸微球被酵素降解之速率(由22%減少至15.5%),另外在動物實驗中,相較於未交聯之玻尿酸,交聯後的玻尿酸微球雖然引起輕微的發炎反應,但仍能有效的刺激膠原蛋白增生。此外,經由磷酸鈣修飾之粒子也可增加材料之相容性,並且延長微球在組織中的代謝時間。因此,由磷酸鈣修飾之交聯玻尿酸微粒具有做為長效型的皮下注射填充物之潛力。
誌謝辭 i
摘要 ii
Abstract iii
Table of Contents iv
List of Figures vi
List of Tables ix
Chapter 1 Introduction 1
1.1 The reasons of facial wrinkles formation 1
1.1.1 Normal skin structure 1
1.1.2 The mechanism of wrinkles formation 2
1.2 Current wrinkles treatments 4
1.2.1 Advantage and limitation of current treatments 4
1.2.2 Type of commercial dermal fillers 5
1.3 Development of delivery strategy in the dermal fillers 8
Chapter 2 Materials and Methods 11
2.1 Materials 11
2.2 Preparation of HA microparticles 12
2.3 Preparation of HA@CaP microparticles 12
2.4 Characterization of microparticles 13
2.5 Mechanical properties of microparticles 13
2.6 Measurement of microparticles swelling 14
2.7 Enzymatic degradation of microparticles 14
2.8 In vitro studies 15
2.8.1 Cell culture conditions 15
2.8.2 Cell cytotoxicity studies 15
2.9 In vivo studies 16
2.9.1 Animal studies 16
2.9.2 Histological analysis 16
2.10 Statistical analysis 17
Chapter 3 Results and Discussion 18
3.1 Characterization of microparticles 18
3.1.1 Synthesis and characterization of HA microparticles 18
3.1.2 Characterization of HA@CaP microparticles 25
3.2 Determination of HA@CaP microparticle composition 33
3.3 Evaluation of microparticles properties 35
3.3.1 Mechanical properties of microparticles 35
3.3.2 Swelling properties of microparticles 36
3.3.3 Determination of microparticle degradation rate 39
3.4 In vitro studies 42
3.4.1 Cytotoxicity 42
3.5 In vivo studies 44
3.5.1 Biological responses of dermis 44
3.5.2 Assessment of collagen distribution 49
Chapter 4 Conclusion 52
References 53
[1] G.J. Fisher, Y. Shao, T. He, Z. Qin, D. Perry, J.J. Voorhees, T. Quan, Reduction of fibroblast size or mechanical force down-regulates TGF-beta receptor: implications for human skin aging, Aging Cell 15 (2016) 67-76.
[2] A.K. GHOSH, Factors Involved in the Regulation of Type I collagen gene expression: Implication in Fibrosis, Society for Experimental Biology and Medicine (2002).
[3] A. Kammeyer, R.M. Luiten, Oxidation events and skin aging, Ageing Res Rev 21 (2015) 16-29.
[4] T. Quan, F. Wang, Y. Shao, L. Rittie, W. Xia, J.S. Orringer, J.J. Voorhees, G.J. Fisher, Enhancing structural support of the dermal microenvironment activates fibroblasts, endothelial cells, and keratinocytes in aged human skin in vivo, The Journal of investigative dermatology 133(3) (2013) 658-67.
[5] R. Kalluri, M. Zeisberg, Fibroblasts in cancer, Nat Rev Cancer 6(5) (2006) 392-401.
[6] Endogenous growth factors as cosmeceuticals, Dermatologic Therapy 20 (2007) 350–359.
[7] E.J. Bradley, C.E. Griffiths, M.J. Sherratt, M. Bell, R.E. Watson, Over-the-counter anti-ageing topical agents and their ability to protect and repair photoaged skin, Maturitas 80(3) (2015) 265-72.
[8] M. Sardy, Role of matrix metalloproteinases in skin ageing, Connect Tissue Res 50(2) (2009) 132-8.
[9] H. Piao, N. Kamiya, F. Cui, M. Goto, Preparation of a solid-in-oil nanosuspension containing L-ascorbic acid as a novel long-term stable topical formulation, Int J Pharm 420(1) (2011) 156-60.
[10] M. Ooe, T. Seki, T. Miura, A. Takada, Comparative evaluation of wrinkle treatments, Aesthetic Plast Surg 37(2) (2013) 424-33.
[11] H.H. Chan, D. Manstein, C.S. Yu, S. Shek, T. Kono, W.I. Wei, The prevalence and risk factors of post-inflammatory hyperpigmentation after fractional resurfacing in Asians, Lasers Surg Med 39(5) (2007) 381-5.
[12] P. Bjerring, M. Clement, L. Heickendorff, H. Egevist, M. Kiernan, Selective non-ablative wrinkle reduction by laser, Journal of cutaneous laser therapy (2000) 9-15.
[13] Trends in the Use of Neurotoxins and Dermal Fillers by US Physicians, J Clin Aesthet Dermatol 7(9) (2014) 14-19.
[14] A. Tezel, G.H. Fredrickson, The science of hyaluronic acid dermal fillers, J Cosmet Laser Ther 10(1) (2008) 35-42.
[15] J. Carruthers, A. Carruthers, S. Humphrey, Introduction to Fillers, Plast Reconstr Surg 136(5 Suppl) (2015) 120S-131S.
[16] J. Kablik, G.D. Monheit, L. Yu, G. Chang, J. Gershkovich, Comparative physical properties of hyaluronic acid dermal fillers, Dermatol Surg 35 Suppl 1 (2009) 302-12.
[17] J. Yeom, S.H. Bhang, B.-S. Kim, M.S. Seo, E.J. Hwang, I.H. Cho, J.K. Park, S.K. Hahn, Effect of Cross-Linking Reagents for Hyaluronic Acid Hydrogel Dermal fillers on tissue augmentation and regeneration, Bioconjugate Chem. 21 (2010) 240-247.
[18] F. Wang, L.A. Garza, S. Kang, et al., IN vivo stimulation of de novo collagen production caused by cross-linked hyaluronic acid dermal filler injections in photodamaged human skin, Archives of Dermatology 143(2) (2007) 155-163.
[19] M. DANNY VLEGGAAR, Facial Volumetric Correction with Injectable Poly-L-Lactic Acid, Dermatol Surg 31 (2005) 1511-1518.
[20] C. Courderot-Masuyer, S. Robin, H. Tauzin, P. Humbert, Evaluation of the Behaviour of Wrinkles Fibroblasts and Normal Aged Fibroblasts in the Presence of Poly-L-Lactic Acid, Journal of Cosmetics, Dermatological Sciences and Applications 02(01) (2012) 20-27.
[21] P. Carol Courderot-Masuyer, P. Sophie Robin, P. Helene Tauzin, M. Philippe Humbert, PhD, Evaluation of lifting and antiwrinkle effects of calcium hydroxylapatite filler. In vitro quantification of contractile forces of human wrinkle and normal aged fibroblasts treated with calcium hydroxylapatite, Journal of Cosmetic Dermatology (2016).
[22] A. Berlin, J.L. Cohen, D.J. Goldberg, Calcium hydroxylapatite for facial rejuvenation, Semin Cutan Med Surg 25(3) (2006) 132-7.
[23] M. Vera B. Morhenn, M. Gottfried Lemperle, PhD, M. Richard L. Gallo, PhD, phagocytosis of different particulate dermal filler substances by human macrophages and skin cells, Dermatologic Surgery 28 (2002) 484-490.
[24] V. Bertucci, C.B. Lynde, Current Concepts in the Use of Small-Particle Hyaluronic Acid, Plast Reconstr Surg 136(5 Suppl) (2015) 132S-138S.
[25] K.M. Chan, R.H. Li, J.W. Chapman, E.M. Trac, J.B. Kobler, S.M. Zeitels, R. Langer, S.S. Karajanagi, Functionalizable hydrogel microparticles of tunable size and stiffness for soft-tissue filler applications, Acta biomaterialia 10(6) (2014) 2563-73.
[26] M. Kawata, K. Azuma, H. Izawa, M. Morimoto, H. Saimoto, S. Ifuku, Biomineralization of calcium phosphate crystals on chitin nanofiber hydrogel for bone regeneration material, Carbohydrate polymers 136 (2016) 964-9.
[27] S.H. Jeong, Y.F. Fan, J.U. Baek, J. Song, T.H. Choi, S.W. Kim, H.E. Kim, Long-lasting and bioactive hyaluronic acid-hydroxyapatite composite hydrogels for injectable dermal fillers: Physical properties and in vivo durability, J Biomater Appl 31(3) (2016) 464-74.
[28] N. SAHINER, X. JIA, One-Step Synthesis of Hyaluronic Acid-Based (sub)micron hydrogel particles-optimization and preliminary characterization, Turk J Chem 32 (2008) 397-409.
[29] A. La Gatta, C. Schiraldi, A. Papa, M. De Rosa, Comparative analysis of commercial dermal fillers based on crosslinked hyaluronan: Physical characterization and in vitro enzymatic degradation, Polymer Degradation and Stability 96(4) (2011) 630-636.
[30] N. Volpi, F. Galeotti, B. Yang, R.J. Linhardt, Analysis of glycosaminoglycan-derived, precolumn, 2-aminoacridone-labeled disaccharides with LC-fluorescence and LC-MS detection, Nat Protoc 9(3) (2014) 541-58.
[31] A.T. Hillel, Z. Nahas, S. Unterman, B. Reid, J. Axelman, D. Sutton, C. Matheson, J. Petsche, J.H. Elisseeff, Validation of a small animal model for soft tissue filler characterization, Dermatol Surg 38(3) (2012) 471-8.
[32] S. Paliwal, S. Fagien, X. Sun, T. Holt, T. Kim, C.K. Hee, D. Van Epps, D.J. Messina, Skin extracellular matrix stimulation following injection of a hyaluronic acid-based dermal filler in a rat model, Plast Reconstr Surg 134(6) (2014) 1224-33.
[33] V.R. Girardi, J.J. Silber, N. Mariano Correa, R. Darío Falcone, The use of two non-toxic lipophilic oils to generate environmentally friendly anionic reverse micelles without cosurfactant. Comparison with the behavior found for traditional organic non-polar solvents, Colloids and Surfaces A: Physicochemical and Engineering Aspects 457 (2014) 354-362.
[34] A.A. Shimojo, A. Pires, R. Lichy, M.H. Santana, The performance of crosslinking with divinyl sulfone as controlled by the interplay between the chemical modification and conformation of hyaluronic acid, Journal of the Brazilian Chemical Society 26(3) (2015) 506-512.
[35] B. Baruah, J.M. Roden, M. Sedgwick, N.M. Correa, D.C. Crans, N.E. Levinger, When Is Water Not Water? Exploring Water Confined in Large Reverse Micelles Using a
Highly Charged Inorganic Molecular Probe, Journal of the american chemical society 128(39) (2006) 12758–12765.
[36] A.A. Shimojo, A.M. Pires, R. Lichy, A.A. Rodrigues, M.H. Santana, The crosslinking degree controls the mechanical, rheological, and swelling properties of hyaluronic acid microparticles, Journal of biomedical materials research. Part A 103(2) (2015) 730-7.
[37] R.A. Surmenev, M.A. Surmeneva, A.A. Ivanova, Significance of calcium phosphate coatings for the enhancement of new bone osteogenesis--a review, Acta biomaterialia 10(2) (2014) 557-79.
[38] W.M. Li, S.Y. Chen, D.M. Liu, In situ doxorubicin-CaP shell formation on amphiphilic gelatin-iron oxide core as a multifunctional drug delivery system with improved cytocompatibility, pH-responsive drug release and MR imaging, Acta biomaterialia 9(2) (2013) 5360-8.
[39] S.-Y. Han, H.S. Han, S.C. Lee, Y.M. Kang, I.-S. Kim, J.H. Park, Mineralized hyaluronic acid nanoparticles as a robust drug carrier, Journal of Materials Chemistry 21(22) (2011) 7996.
[40] B.Q. Lu, Y.J. Zhu, F. Chen, C. Qi, X.Y. Zhao, J. Zhao, Core-shell hollow microspheres of magnetic iron oxide@amorphous calcium phosphate: synthesis using adenosine 5'-triphosphate and application in pH-responsive drug delivery, Chem Asian J 9(10) (2014) 2908-14.
[41] Q. Wang, P. Liu, Y. Sun, T. Gong, M. Zhu, X. Sun, Z. Zhang, Y. Duan, Preparation and properties of biocompatible PS-PEG/calcium phosphate nanospheres, Nanotoxicology 9(2) (2015) 190-200.
[42] Assembly of Aqueous-Cored Calcium Phosphate Nanoparticles for Drug Delivery, Chem. Mater. (2004) 4942-4947.
[43] J. Redepenning, T. Schlessinger, S. Burnham, L. Lippiello, J. Miyano, Characterization of electrolytically prepared brushite and hydroxyapatite coatings on orthopedic alloys, Journal of Biomedical Materials Research Part A 30(3) (1996) 287-294.
[44] J. Buschmann, L. Härter, S. Gao, S. Hemmi, M. Welti, N. Hild, O.D. Schneider, W.J. Stark, N. Lindenblatt, C.M. Werner, Tissue engineered bone grafts based on biomimetic nanocomposite PLGA/amorphous calcium phosphate scaffold and human adipose-derived stem cells, Injury 43(10) (2012) 1689-1697.
[45] N. Sahiner, C. Silan, S. Sagbas, P. Ilgin, S. Butun, H. Erdugan, R.S. Ayyala, Porous and modified HA particles as potential drug delivery systems, Microporous and Mesoporous Materials 155 (2012) 124-130.
[46] L. Sun, L.C. Chow, S.A. Frukhtbeyn, Preparation and Properties of Nanoparticles of Calcium Phosphates With Various Ca/P Ratios, J. Res. Natl. Inst. Stand. Technol. 115(4) (2010) 243-255.
[47] S.H. Jeong, Y.H. Koh, S.W. Kim, J.U. Park, H.E. Kim, J. Song, Strong and Biostable Hyaluronic Acid-Calcium Phosphate Nanocomposite Hydrogel via in Situ Precipitation Process, Biomacromolecules 17(3) (2016) 841-51.
[48] Hyaluronidase from sheep testes Type II.
[49] S. Park, K.Y. Park, I.K. Yeo, S.Y. Cho, Y.C. Ah, H.J. Koh, W.S. Park, B.J. Kim, Investigation of the Degradation-Retarding Effect Caused by the Low Swelling Capacity of a Novel Hyaluronic Acid Filler Developed by Solid-Phase Crosslinking Technology, Ann Dermatol 26(3) (2014) 357-362.
[50] J. Alijotas-Reig, M.T. Fernandez-Figueras, L. Puig, Late-onset inflammatory adverse reactions related to soft tissue filler injections, Clin Rev Allergy Immunol 45(1) (2013) 97-108.
[51] F. Duranti, G. Salti, B. Bovani, M. Calandra, M.L. Rosati, Injectable hyaluronic acid gel for soft tissue augmentation, Dermatologic surgery 24(12) (1998) 1317-1325.
[52] S. SHUSTER, M. M.BLACK, E. McVITIE, The influence of age and sex on skin thickness, skin collagen and density, British Journal of Dermatology (1975) 639-643.
[53] D.Y. Ji, T.F. Kuo, H.D. Wu, J.C. Yang, S.Y. Lee, A novel injectable chitosan/polyglutamate polyelectrolyte complex hydrogel with hydroxyapatite for soft-tissue augmentation, Carbohydrate polymers 89(4) (2012) 1123-30.
[54] F. Grinnell, Fibroblast biology in three-dimensional collagen matrices, Trends in Cell Biology 13(5) (2003) 264-269.
連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊