Water-based preparation of spider silk films as drug delivery matrices

被引:29
作者
Agostini, Elisa [1 ]
Winter, Gerhard [1 ]
Engert, Julia [1 ]
机构
[1] Univ Munich, Dept Pharm Pharmaceut Technol & Biopharmaceut, D-81377 Munich, Germany
关键词
Spider silk; Film; Multilayer; Coating; 2-pyrrolidone; Glycerol; BIOMATERIALS; PROTEINS; RELEASE; SYSTEMS; PARTICLES; DESIGN; CANCER;
D O I
10.1016/j.jconrel.2015.06.025
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The main focus of this work was to obtain a drug delivery matrix characterized by biocompatibility, water insolubility and good mechanical properties. Moreover the preparation process has to be compatible with protein encapsulation and the obtained matrix should be able to sustain release a model protein. Spider silk proteins represent exceptional natural polymers due to their mechanical properties in combination with biocompatibility. As both hydrophobic and slowly biodegrading biopolymers, recombinant spider silk proteins fulfill the required properties for a drug delivery system. In this work, we present the preparation of eADF4(C16) films as drug delivery matrices without the use of any organic solvent. Water-based spider silk films were characterized in terms of protein secondary structure, thermal stability, zeta-potential, solubility, mechanical properties, and water absorption and desorption. Additionally, this study includes an evaluation of their application as a drug delivery system for both small molecular weight drugs and high molecular weight molecules such as proteins. Our investigation focused on possible improvements in the film's mechanical properties including plasticizers in the film matrix. Furthermore, different film designs were prepared, such as: monolayer, coated monolayer, multilayer (sandwich), and coated multilayer. The release of the model protein BSA from these new systems was studied. Results indicated that spider silk films are a promising protein drug delivery matrix, capable of releasing the model protein over 90 days with a release profile close to zero order kinetic. Such films could be used for several pharmaceutical and medical purposes, especially when mechanical strength of a drug eluting matrix is of high importance. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:134 / 141
页数:8
相关论文
共 41 条
[1]   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
[2]   Clinical spectrum of the osmotic-controlled release oral delivery system (OROS), an advanced oral delivery form [J].
Conley, Robert ;
Gupta, Suneel K. ;
Sathyan, Gayatri .
CURRENT MEDICAL RESEARCH AND OPINION, 2006, 22 (10) :1879-1892
[3]   Effects of GLIADEL(R) wafer initial molecular weight on the erosion of wafer and release of BCNU [J].
Dang, WB ;
Daviau, T ;
Ying, P ;
Zhao, Y ;
Nowotnik, D ;
Clow, CS ;
Tyler, B ;
Brem, H .
JOURNAL OF CONTROLLED RELEASE, 1996, 42 (01) :83-92
[4]   Immune responses to implants - A review of the implications for the design of immunomodulatory biomaterials [J].
Franz, Sandra ;
Rammelt, Stefan ;
Scharnweber, Dieter ;
Simon, Jan C. .
BIOMATERIALS, 2011, 32 (28) :6692-6709
[5]   Protein drug stability: A formulation challenge [J].
Frokjaer, S ;
Otzen, DE .
NATURE REVIEWS DRUG DISCOVERY, 2005, 4 (04) :298-306
[6]   Safety and efficacy of Implanon™, a single-rod implantable contraceptive containing etonogestrel [J].
Funk, S ;
Miller, MM ;
Mishell, DR ;
Archer, DF ;
Poindexter, A ;
Schmidt, J ;
Zampaglione, E .
CONTRACEPTION, 2005, 71 (05) :319-326
[7]   Engineered Spider Silk Protein-Based Composites for Drug Delivery [J].
Hardy, John G. ;
Leal-Egana, Aldo ;
Scheibel, Thomas R. .
MACROMOLECULAR BIOSCIENCE, 2013, 13 (10) :1431-1437
[8]   Production and Processing of Spider Silk Proteins [J].
Hardy, John G. ;
Scheibel, Thomas R. .
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY, 2009, 47 (16) :3957-3963
[9]   ZOLADEX - ENDOCRINE AND THERAPEUTIC EFFECTS IN POST-MENOPAUSAL BREAST-CANCER [J].
HARRIS, AL ;
CARMICHAEL, J ;
CANTWELL, BMJ ;
DOWSETT, M .
BRITISH JOURNAL OF CANCER, 1989, 59 (01) :97-99
[10]  
Hermanson K. D., 2012, BIOMATERIALS, V33, P1554