Multilayer films assembled from naturally-derived materials for controlled protein release.
Herein we designed and characterized films composed of naturally derived materials for controlled release of proteins. Traditional drug delivery strategies rely on synthetic or semisynthetic materials or utilize potentially denaturing assembly conditions that are not optimal for sensitive biologics. Layer-by-layer (LbL) assembly of films uses benign conditions and can generate films with various release mechanisms including hydrolysis-facilitated degradation. These use components such as synthetic polycations that degrade into non-natural products. Herein we report the use of a naturally derived, biocompatible and degradable polyanion, poly(β-l-malic acid), alone and in combination with chitosan in an LbL film, whose degradation products of malic acid and chitosan are both generally recognized as safe (GRAS) by the FDA. We have found that films based on this polyanion have shown sustained release of a model protein, lysozyme that can be timed from tens of minutes to multiple days through different film architectures. We also report the incorporation and release of a clinically used biologic, basic fibroblast growth factor (bFGF), which demonstrates the use of this strategy as a platform for controlled release of various biologics.
Departments of Chemistry and §Chemical Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Bryan B
BB
Hsu
Samantha R
SR
Hagerman
Kelsey
K
Jamieson
Jovana
J
Veselinovic
Nicholas
N
O'Neill
Eggehard
E
Holler
Julia Y
JY
Ljubimova
Paula T
PT
Hammond
D000818:Animals; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D008293:Malates / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism; D041681:NIH 3T3 Cells; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism
D003692:Delayed-Action Preparations; D008293:Malates; D011108:Polymers; C074640:poly(malate); D048271:Chitosan; C421864:hen egg lysozyme; D009113:Muramidase