Can ultrasound solve the transport barrier of the neural retina?
OBJECTIVE
Intravitreal injection of nonviral gene complexes may be promising in the treatment of retinal diseases. This study investigates the permeation of lipoplexes and polystyrene nanospheres through the neural retina and their uptake by the retinal pigment epithelium (RPE) either with or without ultrasound application.


METHODS
Anterior parts and vitreous of bovine eyes were removed. The neural retina was left intact or peeled away from the RPE. (Non)pegylated lipoplexes and pegylated nanospheres were applied. After 2 h incubation, the RPE cells were detached and analyzed for particle uptake by flow cytometry and confocal microscopy.


RESULTS
The neural retina is a significant transport barrier for pegylated nanospheres and (non)pegylated lipoplexes. Applying ultrasound improved the permeation of the nanoparticles up to 130 nm.


CONCLUSIONS
Delivery of liposomal DNA complexes to the RPE cells is strongly limited by the neural retina. Ultrasound energy may be a useful tool to improve the neural retina permeability, given the nucleic acid carriers are small enough. Our results underline the importance to design and develop very small carriers for the delivery of nucleic acids to the neural retina and the RPE after intravitreal injection.
Peeters
Liesbeth
L
Laboratory of General Biochemistry and Physical Pharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
Lentacker
Ine
I
Vandenbroucke
Roosmarijn E
RE
Lucas
Bart
B
Demeester
Joseph
J
Sanders
Niek N
NN
De Smedt
Stefaan C
SC
D000818:Animals; D001692:Biological Transport; D002417:Cattle; D004247:DNA / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000493:pharmacokinetics; D015316:Genetic Therapy; D054118:Nanospheres; D010714:Phosphatidylethanolamines / Q000493:pharmacokinetics; D011137:Polystyrenes / Q000493:pharmacokinetics; D000644:Quaternary Ammonium Compounds / Q000493:pharmacokinetics; D012160:Retina / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D014465:Ultrasonics
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D005229:Fatty Acids, Monounsaturated; D010714:Phosphatidylethanolamines; D011137:Polystyrenes; D000644:Quaternary Ammonium Compounds; D004247:DNA; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane