Active growth factor delivery from poly(D,L-lactide-co-glycolide) foams prepared in supercritical CO2

被引:159
作者
Hile, DD [1 ]
Amirpour, ML [1 ]
Akgerman, A [1 ]
Pishko, MV [1 ]
机构
[1] Texas A&M Univ, Dept Chem Engn, College Stn, TX 77843 USA
关键词
basic fibroblast growth factor; poly(D; L-lactide-co-glycolide); supercritical carbon dioxide; controlled release; residual solvents;
D O I
10.1016/S0168-3659(99)00268-0
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A method for the production of microporous poly(D,L-lactide-co-glycolide) foams containing encapsulated proteins using supercritical carbon dioxide is described. Foams generated as aqueous protein emulsions in a polymer-solvent solution were saturated with carbon dioxide at supercritical conditions, and then suddenly supersaturated at ambient conditions causing bubble nucleation and precipitation of the polymer. Proteins contained in the water phase of the emulsion were encapsulated within the foams, including basic fibroblast growth factor (bFGF), an angiogenic factor of interest in tissue engineering applications. The release and activity of bFGF from these foams was determined in vitro and compared with similar porous scaffolds prepared by traditional solvent casting-salt leaching techniques. Total protein release rate was greater from structures made in CO, than those made by the salt leaching technique, however a large initial burst of bFGF was released from the salt leached structures. This initial burst was not observed from the polymer foams processed in CO, and active bFGF was released at a relatively constant rate. Residual methylene chloride levels were measured in the foams made with CO, and were found to be above the limits imposed by the US Pharmacopoeia implying that further solvent removal would be required prior to in vivo use. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:177 / 185
页数:9
相关论文
共 32 条
[1]   Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid polyglycolic acid copolymers [J].
Athanasiou, KA ;
Niederauer, GG ;
Agrawal, CM .
BIOMATERIALS, 1996, 17 (02) :93-102
[2]   A theoretical model of erosion and macromolecular drug release from biodegrading microspheres [J].
Batycky, RP ;
Hanes, J ;
Langer, R ;
Edwards, DA .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1997, 86 (12) :1464-1477
[3]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[4]  
Chaignaud BE, 1997, SYNTHETIC BIODEGRADA
[5]   CONTROLLED DELIVERY SYSTEMS FOR PROTEINS BASED ON POLY(LACTIC GLYCOLIC ACID) MICROSPHERES [J].
COHEN, S ;
YOSHIOKA, T ;
LUCARELLI, M ;
HWANG, LH ;
LANGER, R .
PHARMACEUTICAL RESEARCH, 1991, 8 (06) :713-720
[6]   THE NUCLEATION OF MICROCELLULAR THERMOPLASTIC FOAM WITH ADDITIVES .1. THEORETICAL CONSIDERATIONS [J].
COLTON, JS ;
SUH, NP .
POLYMER ENGINEERING AND SCIENCE, 1987, 27 (07) :485-492
[7]   In vitro assessment of the biological activity of basic fibroblast growth factor released from various polymers and biomatrices [J].
Davies, MJ ;
Mitchell, CA ;
Maley, MAL ;
Grounds, MD ;
Harvey, AR ;
Plant, GW ;
Wood, DJ ;
Hong, Y ;
Chirila, TV .
JOURNAL OF BIOMATERIALS APPLICATIONS, 1997, 12 (01) :31-56
[8]   FORMATION OF MICROPOROUS POLYMER FIBERS AND ORIENTED FIBRILS BY PRECIPITATION WITH A COMPRESSED FLUID ANTISOLVENT [J].
DIXON, DJ ;
JOHNSTON, KP .
JOURNAL OF APPLIED POLYMER SCIENCE, 1993, 50 (11) :1929-1942
[9]   CONTROLLED AND MODULATED RELEASE OF BASIC FIBROBLAST GROWTH-FACTOR [J].
EDELMAN, ER ;
MATHIOWITZ, E ;
LANGER, R ;
KLAGSBRUN, M .
BIOMATERIALS, 1991, 12 (07) :619-626
[10]   Development of technologies aiding large-tissue engineering [J].
Eiselt, P ;
Kim, BS ;
Chacko, B ;
Isenberg, B ;
Peters, MC ;
Greene, KG ;
Roland, WD ;
Loebsack, AB ;
Burg, KJL ;
Culberson, C ;
Halberstadt, CR ;
Holder, WD ;
Mooney, DJ .
BIOTECHNOLOGY PROGRESS, 1998, 14 (01) :134-140