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Scleral permeability of a small, single-stranded oligonucleotide
R Keith Shuler1, Phyllis K Dioguardi, Charles Henjy
1Department of Ophthalmology, Emory University, Atlanta, GA 30322, USA. ophthfe@emory.edu
Summary
Transscleral drug delivery allows small, single-stranded oligonucleotides to cross the sclera. This research quantures the permeability of oligonucleotides for novel ocular treatments.
Area of Science:
- Ophthalmology
- Biomedical Engineering
- Pharmacology
Background:
- Developing effective ocular drug delivery systems is crucial for treating posterior segment eye diseases.
- Transscleral administration offers advantages over traditional posterior segment drug delivery methods, including a larger target area and potentially fewer vision-threatening complications.
Purpose of the Study:
- To determine the in vitro permeability coefficient of a small, single-stranded oligonucleotide across human sclera.
- To evaluate transscleral diffusion of oligonucleotides using two different administration methods.
Main Methods:
- Human sclera mounted in a perfusion chamber was used for in vitro diffusion studies.
- A fluorescein-labeled, single-stranded oligonucleotide was applied to the episcleral surface and intrascleral space.
- Choroidal perfusate was collected hourly for 24 hours to measure oligonucleotide diffusion.
Main Results:
- The permeability constant (K(trans)) for naked oligonucleotide diffusion was 7.67 x 10(-7) cm/s.
- The permeability constant (K(trans)) after intrascleral injection was 1.32 x 10(-7) cm/s.
- Both methods demonstrated successful diffusion of the oligonucleotide across the sclera.
Conclusions:
- Diffusion of naked, single-stranded oligonucleotides across the sclera is feasible using both episcleral application and intrascleral injection.
- This transscleral delivery capability is significant for novel therapeutic strategies utilizing oligonucleotide-based molecules for posterior segment eye diseases.