The degradation, swelling and erosion properties of biodegradable implants prepared by extrusion or compression moulding of poly(lactide-co-glycolide) and ABA triblock copolymers

被引:72
作者
Witt, C
Mäder, K
Kissel, T
机构
[1] Univ Marburg, Dept Pharmaceut & Biopharm, D-35032 Marburg, Germany
[2] Free Univ Berlin, Dept Pharmaceut Biopharm & Biotechnol, D-12169 Berlin, Germany
关键词
ABA-triblock copolymers; poly(lactide-co-glycolide); extrusion; swelling; polymer degradation; EPR-spectroscopy; poly(oxyethylene);
D O I
10.1016/S0142-9612(99)00262-8
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
In the design of parenteral delivery systems the modulation of the biodegradation of a polymer matrix represents a promising strategy to control drug release. We have investigated the degradation of ABA triblock copolymers, consisting of poly(lactide-coglycolide) A-blocks and poly(oxyethylene) B-blocks, and PLG, poly(lactide-co-glycolide), with respect to swelling behaviour, molecular weight loss and polymer erosion. Implants were prepared by either compression moulding or extrusion using a laboratory ram extruder. Insertion of an elastoplastic B-block did not lower the processing temperature, but the entanglement of the polymer chains was significantly reduced as can be seen from the diameters of the extruded rods. The swelling of the rods showed a volume extension of 130% for an ABA containing 50% PEO and 20% for an ABA containing 20% PEG. Using H-1-NMR it was found that protons in the B-blocks of the swollen ABA copolymers were mobile, while the A-blocks remained rigid during incubation. The analysis of the pH inside ABA rods using electron paramagnetic resonance, EPR, gave a pH of 5.2 after incubation with a subsequent increase to pH 6.0 during the first day, approaching the pH of the medium after nearly 33 d. Acidic degradation products did not accumulate inside the ABA rods. Degradation and erosion started immediately upon incubation. By contrast, PLG rods showed the typical profile of degradation and erosion. In this case, the influence of the geometry of the device was insignificant. Consequently, ABA triblock copolymers may widen the spectrum of parenteral drug delivery with regard to release of pH-sensitive drugs as well as erosion-controlled release kinetics. (C) 2000 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:931 / 938
页数:8
相关论文
共 30 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]  
BAILEY FE, 1992, ULLMANNS ENCY IND A, V21
[3]   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
[4]   In vitro evaluation of poly(D,L-lactide-co-glycolide) polymer-based implants containing the alpha-melanocyte stimulating hormone analog, Melanotan-I [J].
Bhardwaj, R ;
Blanchard, J .
JOURNAL OF CONTROLLED RELEASE, 1997, 45 (01) :49-55
[5]   Degradation and protein release properties of microspheres prepared from biodegradable poly(lactide-co-glycolide) and ABA triblock copolymers:: influence of buffer media on polymer erosion and bovine serum albumin release [J].
Bittner, B ;
Witt, C ;
Mäder, K ;
Kissel, T .
JOURNAL OF CONTROLLED RELEASE, 1999, 60 (2-3) :297-309
[6]   FACTORS INFLUENCING THE RELEASE OF PEPTIDES AND PROTEINS FROM BIODEGRADABLE PARENTERAL DEPOT SYSTEMS [J].
BODMER, D ;
KISSEL, T ;
TRAECHSLIN, E .
JOURNAL OF CONTROLLED RELEASE, 1992, 21 (1-3) :129-137
[7]   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
[8]   Polymer bulk erosion [J].
Gopferich, A .
MACROMOLECULES, 1997, 30 (09) :2598-2604
[9]  
Gopferich A, 1996, EUR J PHARM BIOPHARM, V42, P1
[10]   Nanotechnology for biomaterials engineering: Structural characterization of amphiphilic polymeric nanoparticles by H-1 NMR spectroscopy [J].
Hrkach, JS ;
Peracchia, MT ;
Domb, A ;
Lotan, N ;
Langer, R .
BIOMATERIALS, 1997, 18 (01) :27-30