Preparation and characterization of recombinant human bone morphogenetic protein-2/ poly lactic acid sustained release microspheres

doi:10.3969/j.issn.2095-4344.2014.03.011

Abstract

Abstract:

BACKGROUND: Poly lactic acid as an excellent delivery has good biocompatibility.
OBJECTIVE: To prepare recombinant human bone morphogenetic protein-2 (rhBMP-2)/poly lactic acid (PLA) sustained release microspheres, and to study its physical and chemical properties.
METHODS: The rhBMP-2/PLA sustained release microspheres were prepared using w/o/w solvent evaporation method. Scanning electron microscopy, laser particle size, zeta potential, and swelling properties were detected. ELISA kit was utilized for measurement of encapsulation efficiency, drug-loading rate and in vitro drug release rate.
RESULTS AND CONCLUSION: Under the scanning electron microscope, rhBMP-2/PLA sustained release microspheres were approximately circle with excellent dispersion. The uniform spheres were visible with a mean particle size of 839.6 nm. The zeta potential were (-32.93±3.74) mV. The swelling coefficient was 1.157±0.059. The drug-loading rate and encapsulation efficiency of rhBMP-2/PLA sustained release microspheres were (88.943±2.878)% and (0.026±0.001)% respectively. The drug release rate at 1 day was about 10.199%, then the drug release was relatively constant, and till 19 days, the cumulative drug release rate was 54.643%. These findings indicate that the constructed rhBMP-2/PLA sustained release microspheres meet the requirement of the Chinese Pharmacopoeia (10th edition) that the encapsulation efficiency is not less than 80% and the microspheres have a good slow-release function in vitro.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

全文链接：

Key words: biocompatible materials, bone morphogenetic proteins, lactic acid, microspheres, delayed-action preparations

CLC Number:

R318

Ma Li-kun, Ye Peng, Huang Wen-liang, Tian Ren-yuan, Deng Jiang. Preparation and characterization of recombinant human bone morphogenetic protein-2/ poly lactic acid sustained release microspheres[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(3): 395-400.

Figures/Tables 2

References

[1]Rey-Rico A,Silva M,Couceiro J,et al. Osteogenic efficiency of in situ gelling poloxamine systems with and without bone morphogenetic protein-2. Eur Cell Mater. 2011;21(4): 317-340.

[2]Davis HE,Leach JK.Designing bioactive delivery systems for tissue regeneration.Ann Biomed Eng.2011;39(1):1-13.

[3]Talwar R,Di Silvio L,Hughes FJ,et al.Effects of carrier release kinetics on bone morphogenetic protein-2-induced periodontal regeneration in vivo. J Clin Periodontol.2001; 28(4):340-347.

[4]姚爱华,徐为,艾凡荣,等.中空羟基磷灰石微球作为rhBMP-2缓释载体的研究[J].无机材料学报,2011,26(9):974-978.

[5]Fournier E,Passirani C,Montero-Menei CN,et al. Biocompatibility of implantable synthetic polymeric drug carriers: focus on brain biocompatibility. Biomaterials. 2003; 24(19):3311-3331.

[6]冯岚,郭健新,平其能,等.亮丙瑞林缓释微球的研究[J].中国新药与临床杂志, 2004,23(10):680-683.

[7]张海龙,高玲美,邵洪伟.聚乳酸载药微球的制备及应用研究进展[J].西北药学杂志,2010,25(2):158-160.

[8]林丽丽.聚乳酸载药系统的研究进展[J].广东化工,2012,39(6): 90-91.

[9]Wen J,Kim GJ,Leong KW.Poly(D,L-lactide-co-ethyl ethylene phosphate)s as new drug carriers.J Control Release.2003; 92(1-2):39-48.

[10]Chen L,Liu L,Li C,et al.A new growth factor controlled drug release system to promote healing of bone fractures: nanospheres of recombinant human bone morphogenetic-2 and polylactic acid.J Nanosci Nanotechnol.2011;11(4): 3107-3114.

[11]费正奇,胡蕴玉,吴道澄,等. rhBMP-2/聚乳酸与聚乙醇酸共聚物载药微球的制备及成骨活性研究[J].生物医学工程与临床,2006, 10(3):121-124.

[12]Reichert JC,Saifzadeh S,Wullschleger ME,et al.The challenge of establishing preclinical models for segmental bone defect research.Biomaterials. 2009; 30(12): 2149-2163.

[13]Silva AM,Souza WM,Koivisto MB,et al.Miniplate fixation for the repair of segmental mandibular defects filled with autogenous bone in cats.Acta Cir Bras. 2011;26(3):174-180.

[14]Langer R,Vacanti JP.Tissue engineering. Science.1993; 260 (5110):920-926.

[15]Crane GM,Ishaug SL,Mikos AG.Bone tissue engineering. Nat Med.1995;1(12): 1322-1324.

[16]刘昊,张永刚.骨组织工程的研究应用与进展[J].生物骨科材料与临床研究, 2012,9(2):32-34.

[17]Urist MR.Bone: formation by autoinduction. Science.1965; 150(3698):893-899.

[18]丁立峰,周振东,杨军,等.骨形态发生蛋白2基因转染的兔骨髓间充质干细胞复合聚乳酸-聚己内酯支架体外构建载基因仿生骨的实验研究[J].中国矫形外科杂志, 2013,21(9):918-923.

[19]Zuk PA,Zhu M,Mizuno H,et al.Multilineage cells from human adipose tissue: implications for cell-based therapies.Tissue Eng.2001;7(2):211-228.

[20]侯锐,毛天球,陈书军,等.rhBMP-2及rhbFGF对兔骨髓间充质干细胞分化作用长期效应的实验研究[J].医学研究生学报,2004, 17(8):694-697.

[21]Schmidmaier G,Schwabe P,Strobel C,et al.Carrier systems and application of growth factors in orthopaedics.Injury. 2008; 39(Suppl 2):S37-S43.

[22]Hong SJ,Yu HS,Kim HW.Tissue engineering polymeric microcarriers with macroporous morphology and bone-bioactive surface. Macromol Biosci. 2009;9(7): 639-645.

[23]张洁琼,曹健,李艳芳,等.聚乳酸的合成•生物降解及应用研究现状[J].安徽农业科学,2010,38(31):17384-17386.

[24]黄玲玲,姜志华.PLA的合成及改性研究进展[J].合成树脂及塑料, 2010,7(6): 65-69.

[25]Mi FL,Shyu SS,Lin YM,et al.Chitin/PLGA blend microspheres as a biodegradable drug delivery system: a new delivery system for protein.Biomaterials.2003; 24(27):5023-5036.

[26]曲昌锋,陆平,周晓南,等.自身增强聚乳酸接骨板在颌骨骨折中的临床应用体会[J]. 中国实用口腔科杂志,2009,2(11):690-691.

[27]Ogawa Y,Yamamoto M,Okada H,et al.A new technique to efficiently entrap leuprolide acetate into microcapsules of polylactic acid or copoly(lactic/glycolic) acid.Chem Pharm Bull (Tokyo).1988;36(3):1095-1103.

[28]中华人民共和国药典2010年二部[S].国家药典委员会,2009.

[29]Suzuki K,Nakamura T,Matsuura H,et al.A new drug delivery system for local cancer chemotherapy using cisplatin and chitin.Anticancer Res.1995;15(2): 423-426.

[30]Jule E,Nagasaki Y,Kataoka K.Lactose-installed poly(ethylene glycol)-poly(d,l-lactide) block copolymer micelles exhibit fast-rate binding and high affinity toward a protein bed simulating a cell surface. A surface plasmon resonance study.Bioconjug Chem.2003;14(1):177-186.