ABSORBABLE BIOPOLYMERS DERIVED FROM DIMER FATTY-ACIDS

被引:94
作者
DOMB, AJ [1 ]
MANIAR, M [1 ]
机构
[1] NOVA PHARMACEUT CORP,DRUG DELIVERY LABS,BALTIMORE,MD 21224
关键词
BIODEGRADABLE POLYMERS; POLYANHYDRIDE; DIMER FATTY ACID;
D O I
10.1002/pola.1993.080310523
中图分类号
O63 [高分子化学(高聚物)];
学科分类号
070305 ; 080501 ; 081704 ;
摘要
A new class of aliphatic copolyanhydrides was synthesized from nonlinear hydrophobic dimers (FAD) of erucic acid and sebacic acid which possessed the desired physico-chemical and mechanical properties for use as a carrier for drugs. The polymers were synthesized by melt condensation to yield film-forming polymers with molecular weights of 250,000. The copolymer composition was determined by H-1-NMR and gravimetric methods. In vitro degradation studies showed that these polymers degrade following a first-order kinetics with a rapid degradation in the first 10 days leaving a residue which is mostly the FAD comonomer. The drug release from the polymer also followed a first-order kinetics which correlates with the degradation process of the polymer. Drugs like carboplatin, methotrexate, tetracycline, and gentamicin were released in vitro for over 2 weeks and in some cases over 6 weeks. In vivo biocompatibility tests in rats and rabbits in the brain, muscle, and subcutaneously, demonstrated their toxicological inertness and biodegradability. The 1 : 1 copolymer of FAD : SA was selected as a carrier for various applications including a gentamicin-releasing implant which is now undergoing human clinical trials for the treatment of osteomyelitis.
引用
收藏
页码:1275 / 1285
页数:11
相关论文
共 16 条
[1]  
BOGDANSKY S, 1991, P INT S CONTROL REL, V18, P319
[2]   BRAIN BIOCOMPATIBILITY OF A BIODEGRADABLE CONTROLLED RELEASE POLYMER CONSISTING OF ANHYDRIDE COPOLYMER OF FATTY-ACID DIMER AND SEBACIC ACID [J].
BREM, H ;
DOMB, A ;
LENARTZ, D ;
DUREZA, C ;
OLIVI, A ;
EPSTEIN, JI .
JOURNAL OF CONTROLLED RELEASE, 1992, 19 (1-3) :325-329
[3]  
DOMB A, 1991, JUN ACS M PHIL
[4]   POLYANHYDRIDES .1. PREPARATION OF HIGH-MOLECULAR-WEIGHT POLYANHYDRIDES [J].
DOMB, AJ ;
LANGER, R .
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY, 1987, 25 (12) :3373-3386
[5]  
DOMB AJ, IN PRESS BIOPOLYMERS
[6]  
DOMB AJ, 1992, 2ND JER C PHARM SCI
[7]  
DOMB AJ, IN PRESS POLYM ADV T
[8]  
DOMB AJ, IN PRESS POLYM BIOMA
[9]  
HAMILTONBRYD EL, IN PRESS POLYM ADV T
[10]  
HANNIBAL D, 1991, P INT S CONTROL RELE, V18, P672