Expression of MUC5AC in Ocular Surface Epithelial Cells Using Cationized Gelatin Nanoparticles

Decreased production of the mucin MUC5AC in the eye is related to several pathological conditions, including dry eye syndrome. A specific strategy for increasing the ocular levels of MUC5AC is not yet available. Using a plasmid specially designed to encode human MUC5AC, we evaluated the ability of h...

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Bibliographic Details
Published in:Molecular pharmaceutics 2011-10, Vol.8 (5), p.1783-1788
Main Authors: Konat Zorzi, Giovanni, Contreras-Ruiz, Laura, Párraga, Jenny Evelin, López-García, Antonio, Romero Bello, Rafael, Diebold, Yolanda, Seijo, Begoña, Sánchez, Alejandro
Format: Article
Language:English
Subjects:
Animals
Cell Line
Cell Survival
Chemical Phenomena
Chondroitin Sulfates - chemistry
Conjunctiva - metabolism
Cornea - metabolism
Dextran Sulfate - chemistry
DNA - adverse effects
Eye Proteins - genetics
Eye Proteins - metabolism
Gelatin - chemistry
Gene Transfer Techniques - adverse effects
Humans
Materials Testing
Mucin 5AC - genetics
Mucin 5AC - metabolism
Nanoparticles - adverse effects
Nanoparticles - chemistry
Plasmids - adverse effects
Rabbits
Recombinant Proteins - metabolism
RNA, Messenger - metabolism
Spermine - chemistry
Up-Regulation
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Summary:Decreased production of the mucin MUC5AC in the eye is related to several pathological conditions, including dry eye syndrome. A specific strategy for increasing the ocular levels of MUC5AC is not yet available. Using a plasmid specially designed to encode human MUC5AC, we evaluated the ability of hybrid cationized gelatin nanoparticles (NPs) containing polyanions (chondroitin sulfate or dextran sulfate) to transfect ocular epithelial cells. NPs were developed using the ionic gelation technique and characterized by a small size (95%). MUC5AC mRNA and protein were detected in conjunctival cells after in vitro transfection of the NPs. The in vivo administration of the NPs resulted in significantly higher MUC5AC expression in the conjunctiva compared to untreated control and naked plasmid. These results provide a proof-of-concept that these NPs are effective vehicles for gene therapy and candidates for restoring the MUC5AC concentration in the ocular surface.
ISSN:1543-8384
1543-8392
DOI:10.1021/mp200155t