Nanoparticles sustain expression of Flt intraceptors in the cornea and inhibit injury-induced corneal angiogenesis.
OBJECTIVE
To determine whether long-term expression of intraceptors can be achieved using plasmid albumin nanoparticles and whether nanoparticles can inhibit and cause regression of murine corneal neovascularization induced by mechanical-chemical trauma.


METHODS
Albumin nanoparticles encapsulating pCMV.Flt23K were developed as a lyophilized product that is easily redispersed in an aqueous medium. Nanoparticles were injected into the corneas of uninjured BALB/c mice and observed for toxicity for 3 weeks. Entry of nanoparticles into corneal cells was demonstrated through transmission electron microscopy and confocal imaging. Naked pCMV.Flt23K, nanoparticles encapsulating pCMV.Flt23K, or empty pCMV nanoparticles were injected into uninjured mouse corneas. These corneas were subjected to mechanical alkali trauma 3 weeks after injection.


RESULTS
Nanoparticles were nontoxic to the cornea and entered into corneal keratocyte cytoplasm. They persisted for at least 4 weeks in the cornea, expressed effective intraceptor levels for at least 5 weeks, and reduced corneal neovascularization by approximately 40% (P = 0.035) at 5 weeks after administration.


CONCLUSIONS
Albumin nanoparticles are not toxic to the cornea and can express intraceptors for extended periods that are effective in suppressing injury-induced corneal neovascularization.
Jani
Pooja D
PD
Department of Ophthalmology, Medical College of Georgia, Augusta, Georgia 30912, USA.
Singh
Nirbhai
N
Jenkins
Crystal
C
Raghava
Swita
S
Mo
Yun
Y
Amin
Shivan
S
Kompella
Uday B
UB
Ambati
Balamurali K
BK
D000418:Albumins; D000818:Animals; D015153:Blotting, Western; D002057:Burns, Chemical / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002458:Cell Fractionation; D003315:Cornea / Q000378:metabolism* / Q000648:ultrastructure; D016510:Corneal Neovascularization / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003587:Cytomegalovirus / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005126:Eye Burns / Q000139:chemically induced*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000633:toxicity; D010957:Plasmids / Q000235:genetics; D018000:Receptors, Peptide / Q000378:metabolism; D012972:Sodium Hydroxide / Q000633:toxicity; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
D000418:Albumins; C064459:KDEL receptor; D018000:Receptors, Peptide; D012972:Sodium Hydroxide; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1