Peer-Reviewed Journal Details
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Kulltarni, MM,Greiser, U,O'Brien, T,Pandit, A
2011
March
Molecular Pharmaceutics
A Temporal Gene Delivery System Based on Fibrin Microspheres
Published
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Optional Fields
fibrin microspheres gene delivery fibrin scaffold lipoplexes MESENCHYMAL STEM-CELLS NITRIC-OXIDE SYNTHASE HIGH-YIELD ISOLATION MICROBEADS FMB IN-VITRO HINDLIMB ISCHEMIA NEURITE EXTENSION TISSUE RELEASE DIFFERENTIATION
8
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Combining complementary nonviral gene delivery vehicles such as tissue engineering scaffolds and liposomes not only is a promising avenue for development of safe and effective gene delivery system but also provides, an opportunity to design dynamic extended release systems with spatiotemporal control. However, the DNA loading capacity of scaffolds such as fibrin is limited. Fibrin microspheres carrying DNA complexes can be utilized to extend the capacity of fibrin scaffold. Here, in a proof of concept study, the feasibility of fibrin microspheres for extending gene delivery capacity is described. Toward this goal, fibrin microspheres encapsulating lipoplexes were fabricated. The structural and functional integrity of DNA was assessed respectively by gel electrophoresis and an in vivo pilot study, using endothelial nitric oxide synthase (eNOS) as a model therapeutic gene in a rabbit ear ulcer model of compromised wound healing. The results confirmed structural integrity and successful delivery and functional integrity, assessed qualitatively by angiogenic effect of eNOS. Finally, as a step toward development of a "fibrin in fibrin" temporal release system, fibrin microspheres were shown to degrade and release DNA differentially compared to fibrin scaffold. It can thus be concluded that fibrin microspheres can be utilized for gene delivery to extend the capacity of a fibrin scaffold and can form a component of a "fibrin in fibrin" temporal release system,
DOI 10.1021/mp100295z
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