Dexamethasone/PLGA microspheres for continuous delivery of an anti-inflammatory drug for implantable medical devices

被引:246
作者
Hickey, T
Kreutzer, D
Burgess, DJ
Moussy, F
机构
[1] Univ Connecticut, Ctr Hlth, Ctr Biomat, Farmington, CT 06030 USA
[2] Univ Connecticut, Ctr Hlth, Dept Pathol, Farmington, CT 06032 USA
[3] Univ Connecticut, Sch Pharm, Storrs, CT 06269 USA
关键词
microspheres; dexamethasone; continuous release; PLGA; implant; biosensor; anti-inflammatory;
D O I
10.1016/S0142-9612(01)00291-5
中图分类号
R318 [生物医学工程];
学科分类号
0831 [生物医学工程];
摘要
The purpose of this research was to develop polylactic-co-glycolic acid (PLGA) microspheres for continuous delivery of dexamethasone for over a 1-month period. in in effort to suppress the acute and chronic inflammatory reactions to implants such as biosensors, which interfere with their functionality. The microspheres were prepared using an oil-in-water emulsion technique. The oil phase was composed of 9:1 dichloromethane to methanol with dissolved PLGA and dexamethasone. Some microspheres were predegraded for 1 or 2 weeks. Ten percent of polyethylene glycol was added to the oil phase in alternative Formulations to delay drug release. The in vitro release Studies were performed in a constant temperature (37degreesC) warm room, in phosphate-buffered saline at sink conditions. Drug loading and release rates were determined by HPLC-UV analysis. The standard microsphere systems did not provide the desired release profile since, following an initial burst release, a delay of 2 weeks occurred prior to continuous drug release. Predegraded microspheres started to release dexamethasone immediately but the rate of release decreased after only 2 weeks. A mixed standard and predegraded microsphere system was used to avoid this delay and to provide continuous release of dexamethasone for 1 month. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1649 / 1656
页数:8
相关论文
共 45 条
[1]
ABDOU HM, 1990, REMINGTONS PHARM SCI, pCH31
[2]
BIODEGRADABLE MICROSPHERES AS CONTROLLED-RELEASE TETANUS TOXOID DELIVERY SYSTEMS [J].
ALONSO, MJ ;
GUPTA, RK ;
MIN, C ;
SIBER, GR ;
LANGER, R .
VACCINE, 1994, 12 (04) :299-306
[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]
pH and osmotic pressure inside biodegradable microspheres during erosion [J].
Brunner, A ;
Mäder, K ;
Göpferich, A .
PHARMACEUTICAL RESEARCH, 1999, 16 (06) :847-853
[5]
Burgess D., 1994, ENCY PHARM TECHNOLOG, P1
[6]
Delivering neuroactive molecules from biodegradable microspheres for application in central nervous system disorders [J].
Cao, XD ;
Shoichet, MS .
BIOMATERIALS, 1999, 20 (04) :329-339
[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]
Influence of the co-encapsulation of different non-ionic surfactants on the properties of PLGA insulin-loaded microspheres [J].
De Rosa, G ;
Iommelli, R ;
La Rotonda, MI ;
Miro, A ;
Quaglia, F .
JOURNAL OF CONTROLLED RELEASE, 2000, 69 (02) :283-295
[9]
One-month sustained release microspheres of 125I-bovine calcitonin -: In vitro in vivo studies [J].
Diaz, RV ;
Llabrés, M ;
Évora, C .
JOURNAL OF CONTROLLED RELEASE, 1999, 59 (01) :55-62
[10]
Eliaz RE, 2000, J BIOMED MATER RES, V50, P388, DOI 10.1002/(SICI)1097-4636(20000605)50:3<388::AID-JBM13>3.3.CO