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Lingyun Cheng, Ping Lu, Jinkun Liu, William R Freeman, Kristyn Huffman, Ying Xiao, Stephanie Landeros; Scleral permeation of co-administered episcleral drugs. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1704.
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Although intravitreal drug delivery offers high drug bioavailability, there are associated disadvantages such as breaching the eye’s natural protecting barriers and direct neuroretinal drug toxicity. Transscleral drug delivery is a safer alternative with location specific targeting ability. The current study aims to characterize drug permeation through the sclera and choroid upon co-administration of two drugs.
Three model drugs, triamcinolone (TA), diclofenac (DIC), and cyclosporine A (CsA), were administered in pairs or alone onto episclera mounted to a custom made permeation apparatus with upper and lower chambers and a 5-mm orifice. The sclera/choroid disc was trephined from a freshly enucleated rabbit eye globe and drug permeation was monitored by collecting lower chamber fluid for 10 hours at room temperature. Drugs from the lower chamber fluid were quantitated by Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS).
The permeability coefficient (Pc) of the sclera/choroid for single drug administration was TA (6.69±0.398 x10-6cm/sec) ≥ DIC (2.75±0.34) x10-6cm/sec) ≥ CsA (18.19 ± 3.83) x10-8cm/sec) (p<0.05). For dual drug administration, Pc of DIC under DIC+TA was 4.54 ± 0.197 x10-6cm/sec; similarly, Pc of CsA under CsA+TA was 71.37 ± 3.13 x10-8cm/sec. TA significantly promoted sclera/choroid permeability of DIC and CsA upon co-administration (p<0.05).
It seems that co-administration of TA along with DIC or CsA can promote DIC or CsA penetration of the sclera/choroid complex and increase intraocular bioavailability of these two drugs. The study results need to be confirmed by more replications and eye globes of different species.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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