title: Scleral permeability of a small, single-stranded oligonucleotide.
abstract: Developing more effective ocular drug delivery systems is essential to improving the treatment of posterior segment eye disease. The large target area provided by the sclera and potentially less vision threatening complications are advantages of transscleral administration compared to more traditional modalities of drug delivery to the posterior segment. We aimed to determine the permeability coefficient for the in vitro diffusion of a small, single-stranded, oligonucleotide across human sclera. Transscleral permeability was measured by placing 100 microL of 2.96 x 10(-4) mol single-stranded, fluorescein-labeled oligonucleotide (MW = 7998.3) on the episcleral surface of sclera mounted in a perfusion chamber. Fractions of choroidal perfusate were collected hourly for 24 hours. The permeability constant or K(trans) for the transscleral diffusion of the naked, single-stranded, fluorescein-labeled oligonucleotide was 7.67 +/- 1.8 x 10(-7) cm/s (mean +/- SEM, N = 7). The permeability constant or K(trans) after intrascleral injection of the same fluorescein-labeled oligonucleotide was 1.32 +/- 0.42 x 10(-7) (mean +/- SEM, N = 4). This analysis demonstrates that diffusion of a naked, 24-base, single-stranded, fluorescein-labeled oligonucleotide can be accomplished by both of the described methods. The ability to deliver single-stranded oligonucleotides across the sclera may prove to be advantageous given the development of several novel therapeutic strategies that use similar molecules.
authors.affiliation: Department of Ophthalmology, Emory University, Atlanta, GA 30322, USA. ophthfe@emory.edu
authors.forename: R Keith
authors.initials: RK
authors.lastname: Shuler
authors.forename: Phyllis K
authors.initials: PK
authors.lastname: Dioguardi
authors.forename: Charles
authors.initials: C
authors.lastname: Henjy
authors.forename: John M
authors.initials: JM
authors.lastname: Nickerson
authors.forename: L P J
authors.initials: LP
authors.lastname: Cruysberg
authors.forename: Henry F
authors.initials: HF
authors.lastname: Edelhauser
mesh_terms: D004277:DNA, Single-Stranded / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015194:Diffusion Chambers, Culture; D016503:Drug Delivery Systems / Q000295:instrumentation*; D006801:Humans; D066298:In Vitro Techniques; D009841:Oligonucleotides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010539:Permeability; D012590:Sclera / Q000378:metabolism*
chemical_list: D004277:DNA, Single-Stranded; D009841:Oligonucleotides