PREPARATION OF BASIC FIBROBLAST GROWTH FACTOR CHITOSAN MICROSPHERE AND ITS PROPERTIES_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

CHEN Wei ¹ , LIU Zhongqian ² , YUE Yuanhui ³ , WAN Lun ² , HU Jiang ² , LUuml ²

1Department of Orthopaedics, People’s Hospital of Fengjie County, Fengjie Chongqing, 404600, P.R.China;;
2Department of Orthopaedics, Sichuan Provincial People’s Hospital;;
3Department of Orthopaedics, Traditional Medicine Hospital of Chongzhou. Corresponding author: LÜ;
Bo, E-mail: 544061822@qq.com;

Corresponding author：

Keywords：

Basic fibroblast growth factor; Chitosan microsphere; Cross-linking-emulsion method; Chitosan

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Objective To study the release properties of basic fibroblast growth factor (bFGF) chitosan microspheres prepared by cross-linking-emulsion method using chitosan as a carrier material so as to lay a foundation for further study. Methods Using 0.6% sodium tripolyphosphate solution as a crosslinking agent and 1.5% solution of chitosan as a carrier material, bFGF chitosan microspheres were prepared by cross-linking-emulsion method. Laser particle size analyzer and Zeta electric potential analyzer were used to measure the particle diameter distribution, scanning electronic microscope to observe the morphology, and ELISA to determine the drug loading, the encapsulation rate, and the drug release properties. Results The particle size of bFGF chitosan microspheres ranged 20.312-24.152 μm. The microspheres were round with a smooth surface and uniform distribution, and it had no apparent porosity. The drug loading and encapsulation rate of microspheres were (7.57 ± 0.34) mg/g and 95.14% ± 1.58%, respectively. The bFGF chitosan microspheres could continuously release bFGF for 24 days; the bFGF level increased gradually with time and reached (820.45 ± 21.34) ng/mL at 24 days; and the microspheres had a burst effect, and the burst rate was 18.08%, and the accumulative release rate of the microspheres reached 82.05% during 24 days. Conclusion It is easy-to-operate to prepare the bFGF chitosan microspheres with the cross-linking-emulsion method. The bFGF chitosan microspheres have smooth surface, uniform distribution, and no apparent porosity.

Citation： CHEN Wei,LIU Zhongqian,YUE Yuanhui,WAN Lun,HU Jiang,LUuml,Bo. PREPARATION OF BASIC FIBROBLAST GROWTH FACTOR CHITOSAN MICROSPHERE AND ITS PROPERTIES. Chinese Journal of Reparative and Reconstructive Surgery, 2012, 26(8): 989-992. doi: Copy

1.	Okada-Ban M, Thiery JP, Jouanneau J. Fibroblast growth factor-2. Int J Biochem Cell Biol, 2000, 32(3): 263-267.
2.	Jeon O, Kang S W, Lim HW. Long-term and zero-order release of basic fibroblast growth factor from heparin-conjugated poly (l-lactide-co-glycolide) nanospheres and fibringel. Biomaterials, 2005, 8: 30-32.
3.	张纲, 谭颖徽, 卢来春, 等. bFGF-PLA缓释纳米微球的制备及体外释药的研究. 重庆医学, 2006, 35(11): 1002-1004.
4.	黄鑫, 孟国林, 刘建, 等. rhBMP-2壳聚糖微球的制备及体外检测. 中国矫形外科杂志, 2009, 17(15): 1172-1174.
5.	李可欣, 陈大为, 赵秀丽, 等. 分散-交联法制备氟尿嘧啶壳聚糖微球的研究. 中国药学杂志, 2005, 40(18): 1392-1395.
6.	Subramanian A, Lin HY, Vu D, et al. Synthesis and evaluation of scaffolds prepared from chitosan fibers for potential use in cartilage tissue engineering. Biomed Sci Instrum, 2004, 40: 117-122.
7.	Wang AH, Chen XG, Liu CS, et al. Preparation and characteristics of chitosan microspheres in different acetylation as drug carrier system. J Microencapsul, 2008, 26(7): 593-602.
8.	Zhang Y, Cheng X, Whng J, et al. Novel chitosan/collagen scaffold containing transforming growth factor-beta l DNA for periodontal tissue engineering. Biochem Biophys Res Commun, 2006, 344(1): 362-369.
9.	Wang QZ, Chen XG, Li ZX, et al．Preparation and blood coagulation evaluation of chitosan microspheres. J Mater Sci Mater Med, 2008, 19 (3): 1371-1377.
10.	Grenha A, Remuñán-López C, Carvalho EL, et al．Microspheres containing lipid/chitosan nanoparticles complexes for pulmonary delivery of therapeutic proteins. Eur J Pharm Biopharm, 2008, 69(1): 83-93.
11.	Ozba?-Turan S, Akbu?a J, Aral C. Controlled release of interleukin-2 from chitosan microspheres. J Pharm Sci, 2002, 91(5): 1245-1251.
12.	刘利萍, 李苹, 吴泽志, 等. 5-Fu壳聚糖/丝素复合磁微球的制备及体外性质研究. 中国药学杂志, 2003, 38(10): 774-777.
13.	郭保林, 高青雨. 壳聚糖的功能化及其作为生物医用高分子材料的研究进展. 胶体与聚合物, 2006, 24(2): 30-33.
14.	Sinha VR, Singla AK, Wadhawan S, et al. Chitosan microspheres as a potential carrier for drugs. Int J Pharm, 2004, 274(1-2): 1-33.
15.	何荣芬, 袁刚. 磁性壳聚糖微球研究进展. 检验医学与临床, 2011, 8(12): 1500-1502.
16.	Shu XZ, Zhu KJ. Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure. Int J Pharm, 2002, 233(1-2): 217-225.
17.	Calvo PC, Remuñán-López C, Vila-Jato JL, et al. Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers. J Appl Poly Sci, 1997, 63(1): 125-132.
18.	陈思, 董念国, 史嘉玮, 等. 制备壳聚糖微球体外缓释TGF-β1的研究. 生物医学工程研究, 2008, 27(2): 125-128.
19.	石晶, 鲍永利, 乌垠, 等. 离子凝聚法制备负载流感疫苗的壳聚糖微球. 高等学校化学学报, 2008, 29 (11): 2308-2311.
20.	曾春, 蔡道章, 全大萍, 等. TGF-β1壳聚糖缓释微球的制备和体外检测. 中山大学学报: 医学科学版, 2005, 26(3): 347-350.
21.	张越, 高俊刚, 杜红霞, 等. 紫檀茋壳聚糖微球的制备及其体外释放性能. 合成化学, 2011, 19 (3): 304-309.
22.	陈志奎, 林礼务, 林琦, 等. 眼镜蛇毒细胞毒素缓释微球制备及体外性质研究. 中国生化药物杂志, 2008, 29(3): 161-164.

1. Okada-Ban M, Thiery JP, Jouanneau J. Fibroblast growth factor-2. Int J Biochem Cell Biol, 2000, 32(3): 263-267.
2. Jeon O, Kang S W, Lim HW. Long-term and zero-order release of basic fibroblast growth factor from heparin-conjugated poly (l-lactide-co-glycolide) nanospheres and fibringel. Biomaterials, 2005, 8: 30-32.
3. 张纲, 谭颖徽, 卢来春, 等. bFGF-PLA缓释纳米微球的制备及体外释药的研究. 重庆医学, 2006, 35(11): 1002-1004.
4. 黄鑫, 孟国林, 刘建, 等. rhBMP-2壳聚糖微球的制备及体外检测. 中国矫形外科杂志, 2009, 17(15): 1172-1174.
5. 李可欣, 陈大为, 赵秀丽, 等. 分散-交联法制备氟尿嘧啶壳聚糖微球的研究. 中国药学杂志, 2005, 40(18): 1392-1395.
6. Subramanian A, Lin HY, Vu D, et al. Synthesis and evaluation of scaffolds prepared from chitosan fibers for potential use in cartilage tissue engineering. Biomed Sci Instrum, 2004, 40: 117-122.
7. Wang AH, Chen XG, Liu CS, et al. Preparation and characteristics of chitosan microspheres in different acetylation as drug carrier system. J Microencapsul, 2008, 26(7): 593-602.
8. Zhang Y, Cheng X, Whng J, et al. Novel chitosan/collagen scaffold containing transforming growth factor-beta l DNA for periodontal tissue engineering. Biochem Biophys Res Commun, 2006, 344(1): 362-369.
9. Wang QZ, Chen XG, Li ZX, et al．Preparation and blood coagulation evaluation of chitosan microspheres. J Mater Sci Mater Med, 2008, 19 (3): 1371-1377.
10. Grenha A, Remuñán-López C, Carvalho EL, et al．Microspheres containing lipid/chitosan nanoparticles complexes for pulmonary delivery of therapeutic proteins. Eur J Pharm Biopharm, 2008, 69(1): 83-93.
11. Ozba?-Turan S, Akbu?a J, Aral C. Controlled release of interleukin-2 from chitosan microspheres. J Pharm Sci, 2002, 91(5): 1245-1251.
12. 刘利萍, 李苹, 吴泽志, 等. 5-Fu壳聚糖/丝素复合磁微球的制备及体外性质研究. 中国药学杂志, 2003, 38(10): 774-777.
13. 郭保林, 高青雨. 壳聚糖的功能化及其作为生物医用高分子材料的研究进展. 胶体与聚合物, 2006, 24(2): 30-33.
14. Sinha VR, Singla AK, Wadhawan S, et al. Chitosan microspheres as a potential carrier for drugs. Int J Pharm, 2004, 274(1-2): 1-33.
15. 何荣芬, 袁刚. 磁性壳聚糖微球研究进展. 检验医学与临床, 2011, 8(12): 1500-1502.
16. Shu XZ, Zhu KJ. Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure. Int J Pharm, 2002, 233(1-2): 217-225.
17. Calvo PC, Remuñán-López C, Vila-Jato JL, et al. Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers. J Appl Poly Sci, 1997, 63(1): 125-132.
18. 陈思, 董念国, 史嘉玮, 等. 制备壳聚糖微球体外缓释TGF-β1的研究. 生物医学工程研究, 2008, 27(2): 125-128.
19. 石晶, 鲍永利, 乌垠, 等. 离子凝聚法制备负载流感疫苗的壳聚糖微球. 高等学校化学学报, 2008, 29 (11): 2308-2311.
20. 曾春, 蔡道章, 全大萍, 等. TGF-β1壳聚糖缓释微球的制备和体外检测. 中山大学学报: 医学科学版, 2005, 26(3): 347-350.
21. 张越, 高俊刚, 杜红霞, 等. 紫檀茋壳聚糖微球的制备及其体外释放性能. 合成化学, 2011, 19 (3): 304-309.
22. 陈志奎, 林礼务, 林琦, 等. 眼镜蛇毒细胞毒素缓释微球制备及体外性质研究. 中国生化药物杂志, 2008, 29(3): 161-164.

Chinese Journal of Reparative and Reconstructive Surgery

PREPARATION OF BASIC FIBROBLAST GROWTH FACTOR CHITOSAN MICROSPHERE AND ITS PROPERTIES

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