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Michael George Lancina, Shahid Husain, Sudha Singh, Hu Yang; Dendrimer Nanofibers for Ocular Drug Delivery. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
PAMAM dendrimers have been investigated as a potential platform for a number of ocular drugs, but they are unstable when stored in aqueous solution. This work adapts dendrimer based nanofibers (DNF) to deliver a glaucoma drug brimonidine tartrate (BT) and investigates the drug release kinetics and ocular biocompatibility of the material. We hypothesize DNF mats can serve as solid form alternative to saline eye drops.
BT was incorporated into DNF by physical entrapment during electrospinning. Drug release kinetics were measured in vitro under static diffusion and dynamic flow conditions. Cornea permeability to BT was measured using fresh rabbit corneas and Franz diffusion cells. Cytotoxicity was measured by WST-1 assay after 24 hour incubation. In vivo efficacy was accessed by intra ocular pressure (IOP) response to a one time dose in normotensive rats (n=4). Statistical analysis was performed using two-tailed student’s t-tests except for the viability measurements, where a one-way t-test was performed.
DNF slowed BT release by 61% over 90 minutes compared to saline eye drops in diffusion tests (p=0.006) and 56% over the first 10 minutes of simulated tear flow tests. (p=0.004) DNF had no effect on the permeability coefficient of live corneas to BT (6.43x10-6 cm/s) compared to saline solution (6.90x10-6 cm/s). DNF showed no significant reduction in cell viability at the therapeutic concentrations needed for the BT loading density used (75µM). (p=0.989) DNF induced equivalent changes in IOP as BT eye drops at all time points measured. (pmin=0.097 at 4hr post treatment)
Results of our animal trial are consistent with our hypothesis that DNF can at minimum match the performance of saline eye drops with no biocompatibility issues. As a whole this study serves as a proof of concept for the use of these materials to delivery ocular drugs. Further modification of the dendrimers is needed for DNF to exceed the drug delivery efficiency of eye drops under in vivo conditions.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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