Microfluidic Synthesis of Biodegradable Polyethylene-Glycol Microspheres for Controlled Delivery of Proteins and DNA Nanoparticles

被引:33
作者
Deveza, Lorenzo [1 ,2 ]
Ashoken, Jothikritika [3 ]
Castaneda, Gloria [4 ]
Tong, Xinming [4 ]
Keeney, Michael [4 ]
Han, Li-Hsin [4 ]
Yang, Fan [1 ,4 ]
机构
[1] Stanford Univ, Dept Bioengn, 300 Pasteur Dr,Edwards R105,MC5341, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, MSTP Program, Stanford, CA 94305 USA
[3] San Jose State Univ, Dept Biol Sci, San Jose, CA 95192 USA
[4] Stanford Univ, Dept Orthopaed Surg, Stanford, CA 94305 USA
关键词
controlled release; drug delivery; biodegradable; microspheres; hydrogels; FIBROBLAST-GROWTH-FACTOR; DRUG-DELIVERY; GENE DELIVERY; RELEASE; MONODISPERSE; MICROPARTICLES; MICROGELS; CELLS; ENCAPSULATION; DEVICE;
D O I
10.1021/ab500051v
中图分类号
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号
0805 ; 080501 ; 080502 ;
摘要
Polymeric microspheres represent an injectable platform for controlling the release of a variety of biologics; microspheres may be combined in a modular fashion to achieve temporal release of two or more biomolecules. Microfluidics offers a versatile platform for synthesizing uniform polymeric microspheres harboring a variety of biologics under relatively mild conditions. Poly(ethylene glycol) (PEG) is a bioinert polymer that can be easily tailored to encapsulate and control the release of biologics. In this study, we report the microfluidic synthesis of biodegradable PEG-based microparticles for controlled release of growth factors or DNA nanoparticles. Simple changes in microfluidic design increased the rate of microparticle formation and controlled the size of the microspheres. Mesh size and degradation rate were controlled by varying the PEG polymer weight percent from 7.5 to 15% (w/v), thus tuning the release of growth factors and DNA nanoparticles, which retained their bioactivity in assays of cell proliferation and DNA transfection, respectively. This platform may provide a useful tool for synthesizing microspheres for use as injectable carriers to achieve coordinated growth factor or DNA nanoparticle release in therapeutic applications.
引用
收藏
页码:157 / 165
页数:9
相关论文
共 29 条
[21]   Controlling network structure in degradable thiol-acrylate biomaterials to tune mass loss behavior [J].
Rydholm, Amber E. ;
Reddy, Sirish K. ;
Anseth, Kristi S. ;
Bowman, Christopher N. .
BIOMACROMOLECULES, 2006, 7 (10) :2827-2836
[22]   Smart Microgel Capsules from Macromolecular Precursors [J].
Seiffert, Sebastian ;
Thiele, Julian ;
Abate, Adam R. ;
Weitz, David A. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2010, 132 (18) :6606-6609
[23]   Dynamic pattern formation in a vesicle-generating microfluidic device [J].
Thorsen, T ;
Roberts, RW ;
Arnold, FH ;
Quake, SR .
PHYSICAL REVIEW LETTERS, 2001, 86 (18) :4163-4166
[24]   Preparation and characterization of P(MAA-g-EG) nanospheres for protein delivery applications [J].
Torres-Lugo, M ;
Peppas, NA .
JOURNAL OF NANOPARTICLE RESEARCH, 2002, 4 (1-2) :73-81
[25]   Microfluidic Encapsulation of Cells in Polymer Microgels [J].
Velasco, Diego ;
Tumarkin, Ethan ;
Kumacheva, Eugenia .
SMALL, 2012, 8 (11) :1633-1642
[26]   Preparation of Monodisperse Biodegradable Polymer Microparticles Using a Microfluidic Flow-Focusing Device for Controlled Drug Delivery [J].
Xu, Qiaobing ;
Hashimoto, Michinao ;
Dang, Tram T. ;
Hoare, Todd ;
Kohane, Daniel S. ;
Whitesides, George M. ;
Langer, Robert ;
Anderson, Daniel G. .
SMALL, 2009, 5 (13) :1575-1581
[27]   Gene delivery to human adult and embryonic cell-derived stem cells using biodegradable nanoparticulate polymeric vectors [J].
Yang, F. ;
Green, J. J. ;
Dinio, T. ;
Keung, L. ;
Cho, S-W ;
Park, H. ;
Langer, R. ;
Anderson, D. G. .
GENE THERAPY, 2009, 16 (04) :533-546
[28]   Cell-demanded release of VEGF from synthetic, biointeractive cell-ingrowth matrices for vascularized tissue growth [J].
Zisch, AH ;
Lutolf, MP ;
Ehrbar, M ;
Raeber, GP ;
Rizzi, SC ;
Davies, N ;
Schmökel, H ;
Bezuidenhout, D ;
Djonov, V ;
Zilla, P ;
Hubbell, JA .
FASEB JOURNAL, 2003, 17 (13) :2260-+
[29]   Hydrolytically Degradable Poly(Ethylene Glycol) Hydrogel Scaffolds with Tunable Degradation and Mechanical Properties [J].
Zustiak, Silviya P. ;
Leach, Jennie B. .
BIOMACROMOLECULES, 2010, 11 (05) :1348-1357