Silk fibroin encapsulated powder reservoirs for sustained release of adenosine

被引:85
作者
Pritchard, Eleanor M. [1 ]
Szybala, Cory [2 ]
Boison, Detlev [2 ]
Kaplan, David L. [1 ]
机构
[1] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA
[2] Robert S Dow Neurobiol Labs, Portland, OR 97232 USA
关键词
Controlled release; Silk fibroin; Biomaterials; Adenosine; Epilepsy; Encapsulated reservoir; DRUG-RELEASE; IN-VITRO; DELIVERY; POLYMER; CELL; DEGRADATION; ETHYLCELLULOSE; BIOMATERIALS; MECHANISMS; COATINGS;
D O I
10.1016/j.jconrel.2010.01.035
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Due to its unique properties, silk fibroin was studied as a biodegradable polymer vehicle for sustained, local delivery of the anticonvulsant adenosine from encapsulated reservoirs. Silk is a biologically derived protein polymer that is biocompatible, mechanically strong and degrades to non-toxic products in vivo. To achieve local, sustained, controlled adenosine release from fully degradable implants, solid adenosine powder reservoirs were coated with silk fibroin. Material properties of the silk coating including thickness, crystallinity and morphology were investigated to assess the relationships between silk coating biomaterial features and adenosine release from silk encapsulated reservoirs. Reservoir coating thickness was varied through manipulation of the silk coating solution concentration and number of coatings applied. Release studies were also performed in proteinase type XIV to model the effects of degradation. Increasing the harder to diffusion, either by increasing coating thickness or crystallinity was found to delay adenosine burst, decrease average daily release rate, and increase duration of release. In the case of encapsulated reservoirs coated with eight layers of 8% (w/v) silk, a linear release profile was observed and adenosine release was sustained for 14 days. The ability to achieve nearly constant release for 2 weeks for adenosine via control of the silk coating suggests these encapsulated reservoirs represent a novel system for delivering adenosine. We anticipate that this approach could also be extended to other implant needs and small-molecule drugs to treat a range of clinical needs. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:159 / 167
页数:9
相关论文
共 56 条
[1]   FILM COATING OF PELLETS WITH INSOLUBLE POLYMERS OBTAINED IN-SITU CROSS-LINKING IN THE FLUIDIZED-BED [J].
ABLETSHAUSER, CB ;
SCHNEIDER, R ;
RUPPRECHT, H .
JOURNAL OF CONTROLLED RELEASE, 1993, 27 (02) :149-156
[2]   Mechanisms of controlled drug release from drug-eluting stents [J].
Acharya, Ghanashyam ;
Park, Kinam .
ADVANCED DRUG DELIVERY REVIEWS, 2006, 58 (03) :387-401
[3]   Silk-based biomaterials [J].
Altman, GH ;
Diaz, F ;
Jakuba, C ;
Calabro, T ;
Horan, RL ;
Chen, JS ;
Lu, H ;
Richmond, J ;
Kaplan, DL .
BIOMATERIALS, 2003, 24 (03) :401-416
[4]   The adenosine kinase hypothesis of epileptogenesis [J].
Boison, Deflev .
PROGRESS IN NEUROBIOLOGY, 2008, 84 (03) :249-262
[5]   Adenosine-based cell therapy approaches for pharmacoresistant epilepsies [J].
Boison, Detlev .
NEURODEGENERATIVE DISEASES, 2007, 4 (01) :28-33
[6]   Adenosine kinase, epilepsy and stroke: mechanisms and therapies [J].
Boison, Detlev .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2006, 27 (12) :652-658
[7]   Adenosine augmentation therapies (AATs) for epilepsy: Prospect of cell and gene therapies [J].
Boison, Detlev .
EPILEPSY RESEARCH, 2009, 85 (2-3) :131-141
[8]   MECHANISMS TO CONTROL DRUG RELEASE FROM PELLETS COATED WITH A SILICONE ELASTOMER AQUEOUS DISPERSION [J].
DAHL, TC ;
SUE, IIT .
PHARMACEUTICAL RESEARCH, 1992, 9 (03) :398-405
[9]   Natural polymers for gene delivery and tissue engineering [J].
Dang, Jiyoung M. ;
Leong, Kam W. .
ADVANCED DRUG DELIVERY REVIEWS, 2006, 58 (04) :487-499
[10]   Therapeutic applications of implantable drug delivery systems [J].
Dash, AK ;
Cudworth, GC .
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, 1998, 40 (01) :1-12