A novel approach to stabilization of protein drugs in poly(lactic-co-glycolic acid) microspheres using agarose hydrogel

被引:61
作者
Wang, N
Wu, XS
机构
[1] Long Isl Univ, Arnold & Marie Schwartz Coll Pharm & Hlth Sci, Div Pharmaceut & Ind Pharm, Brooklyn, NY 11201 USA
[2] Polytech Univ, Herman F Mark Polymer Res Inst, Brooklyn, NY 11201 USA
关键词
protein stabilization; poly(lactic-co-glycolic acid); microspheres; agarose; hydrogel; heterogeneous/domain structure;
D O I
10.1016/S0378-5173(97)00339-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A novel approach has been taken to stabilize protein drugs in poly(lactic-co-glycolic acid) (PLGA) microspheres. This approach creates a new protein drug delivery system, which is based on the combination of agarose hydrogel particles and PLGA microspheres. This combination produces a heterogeneously structured polymeric composite. The protein drug molecules are encapsulated in the agarose hydrogel particles and the drug-containing agarose hydrogel particles are further dispersed in the PLGA microspheres. One PLGA microsphere may contain many agarose hydrogel particles to form a PLGA-agarose composite microsphere. The PLGA-agarose composite microspheres have spherical shape and a smooth surface. They possess a normal or Gaussian size distribution and an average diameter of 150 mu m. The PLGA-agarose composite microspheres have higher protein loading efficiency than that of the conventional PLGA microspheres. The hydration of the PLGA-agarose composite microsphere matrix is faster than that of the conventional PLGA microspheres. Protein drugs can be slowly released from the PLGA-agarose composite microspheres. The agarose hydrogel particles can stabilize protein drugs in the PLGA matrix, which is the major advantage of this novel protein drug delivery system over the conventional PLGA microspheres. (C) 1998 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:1 / 14
页数:14
相关论文
共 32 条
[1]   INCREASED THERMAL-STABILITY OF PROTEINS IN THE PRESENCE OF SUGARS AND POLYOLS [J].
BACK, JF ;
OAKENFULL, D ;
SMITH, MB .
BIOCHEMISTRY, 1979, 18 (23) :5191-5196
[2]  
BAKER RW, 1987, CONTROLLED RELEASE B, P29
[3]   THE ACCELERATION OF DEGRADATION-CONTROLLED DRUG DELIVERY FROM POLYESTER MICROSPHERES [J].
CHA, Y ;
PITT, CG .
JOURNAL OF CONTROLLED RELEASE, 1989, 8 (03) :259-265
[4]  
CHANG TMS, 1976, J BIOENG, V1, P25
[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]  
DONBROW M, 1992, MICROCAPSULES NANOPA, P17
[7]   PARTICLE-SIZE AND SIZE DISTRIBUTION OF POLY(BUTYL-2-CYANOACRYLATE) NANOPARTICLES .1. INFLUENCE OF PHYSICOCHEMICAL FACTORS [J].
DOUGLAS, SJ ;
ILLUM, L ;
DAVIS, SS ;
KREUTER, J .
JOURNAL OF COLLOID AND INTERFACE SCIENCE, 1984, 101 (01) :149-158
[8]  
FONG JW, 1988, CONTROLLED RELEASE S, V1, P81
[9]   DISSOLUTION CONTROLLED DRUG-RELEASE FROM AGAROSE BEADS [J].
HAGLUND, BO ;
UPADRASHTA, SM ;
NEAU, SH ;
CUTRERA, MA .
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 1994, 20 (06) :947-959
[10]   FEASIBILITY OF AGAROSE MICROBEADS WITH XENOGENEIC ISLETS AS A BIOARTIFICIAL PANCREAS [J].
IWATA, H ;
KOBAYASHI, K ;
TAKAGI, T ;
OKA, T ;
YANG, H ;
AMEMIYA, H ;
TSUJI, T ;
ITO, F .
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, 1994, 28 (09) :1003-1011