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Abstract #13174 Published in IGR 7-3
The influence of intraocular pressure on the transscleral diffusion of high-molecular-weight compounds
Cruysberg LP; Nuijts RM; Geroski DH; Gilbert JA; Hendrikse F; Edelhauser HFInvestigative Ophthalmology and Visual Science 2005; 46: 3790-3794
PURPOSE: To evaluate the effects of intraocular pressure on the permeability of the human sclera to high-molecular-weight compounds. METHODS: Human transscleral permeability to FITC-albumin (70 kDa) and 70-kDa and 150-kDa FITC-dextran was determined at transscleral pressures from 0 to 60 mmHg. For each compound at each pressure, six to eight experiments were performed. Scleral sections were mounted in a two-compartment perfusion chamber. Temperature was maintained at 37 degrees C. Fractions of choroidal perfusate were collected, and fluorescence was measured with a spectrofluorometer. From these data, scleral permeability K(trans) (in centimeters per second) was calculated. RESULTS: Permeability to FITC-albumin was decreased by approximately one half when pressure was elevated from 0 to 30 mmHg (P < 0.05). No significant differences in permeability to 70-kDa FITC-dextran were observed at pressures from 0 to 60 mmHg. Permeability to 150-kDa FITC-dextran decreased by a little more than one half when transscleral pressure was raised from 0 to 15 mmHg and was approximately 10 times lower at 60 mmHg than at 0 mmHg (P < 0.01). CONCLUSIONS: Human sclera was permeable to compounds with a molecular weight of up to 150 kDa at transscleral pressures ranging from 0 to 60 mmHg. Transscleral diffusion was relatively unaffected by the pressure gradient, although for 150-kDa FITC-dextran at 60 mmHg a 10-fold decrease was observed compared with that at 0 mmHg. These experiments suggest that high-molecular-weight compounds (e.g., immunoglobulins and oligonucleotides) could be effectively delivered transsclerally to the intraocular tissues under circumstances of physiological or elevated intraocular pressure.
Dr. L.P. Cruysberg, Department of Ophthalmology, Emory University, Atlanta, GA 30322, USA
Classification:
11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)
