Purchase this article with an account.
D. Tang, S. Xiao, J.M. Donaldson, D. Borchman; Drug Delivery Across the Cornea by PEGylated Liposomes in vitro and in vivo . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5100.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Our purpose was to design PEGylated liposomes to deliver drugs across the cornea which represents the greatest barrier for drug penetration into the anterior chamber.
Liposomes were composed of DOTAP/DOPE/DOPE–PEG750 (1/1/0.025, mol/mol/mol) and CHEMS/DOPE/DOPE–PEG750 (1/1/0.025, mol/mol/mol). New Zealand rabbits were used. Liposomes were prepared by five freeze–thaw cycles, followed by 10 extrusions through membranes with a100 nm pore size. The fluorophore 8–aminonaphthalene–1,3,6–trisulfonic acid, disodium salt (ANTS) was trapped in the liposomes as a drug model so that delivery could be quantified. Free ANTS was removed by a Sephadex G–50 chromatography column and selected fractions were purified using a spin column. The same concentration of ANTS–PBS solution was used as control. Drug permeation through the cornea in vitro was conducted by using freshly enucleated eyeballs onto which the end of an 8 mm–diameter tube was sealed onto the cornea with Newskin liquid bandage (Medtech, Jackson, WY). The liposomes containing ANTS and control ANTS–PBS solution were applied respectively to the cornea through the open end of the tube. Drug permeation through the cornea in vivo was conducted by applying of the liposomes and control solutions to the rabbit's conjunctival sac of left and right eyes, respectively.
Data from in vitro experiments show that the amount of ANTS delivered to the aqueous humor is 1.35 (n=6) and 2.15 (n=12) fold higher for solutions containing DOTAP/DOTAP/DOPE–PEG750 liposomes and CHEMS/DOPE/PEG750 liposomes, respectively, compared with controls that did not contain liposomes. Data from in vivo experiments show that the amount of ANTS delivered to the aqueous humor by DOTAP/DOPE/DOPE–PEG750 liposomes is 1.62 (n=3) and 10.06 (n=3) fold higher than controls, whereas CHEMS/DOPE/DOPE–PEG750 liposomes is 1.21 (n=3) and 1.25 (n=3) fold higher than controls.
Both PEGylated DOTAP and CHEMS containing liposomes increase drug penetration through the cornea. In future studies we propose to maximize drug delivery efficacy by adjusting the composition of the liposomes.
This PDF is available to Subscribers Only