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E. S. Kim, S. J. Lee, J. A. Zaffos, C. Durairaj, U. B. Kompella, D. H. Geroski, H. F. Edelhauser; Transscleral Permeability of Doxorubicin Nanoparticles. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4784.
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To compare the transscleral permeability of doxorubicin (DOX) to nanoparticle encapsulated doxorubicin (NPDOX).
Human scleral tissue was mounted in a Lucite block perfusion chamber. The outer surface of the sclera was exposed to 200 µL DOX (MW 579.98; 0.488 mg/mL), NPDOX (MW: 579.98; 0.488 mg/mL), or Balanced Salt Solution (BSS) as a control for 24 hrs. Each chamber was perfused with BSS on the choroidal side of the sclera at a rate of 3.0 µL/min. Perfusate fractions were collected every 2 hours over a 24 hr period. Doxorubicin has innate fluorescence with an Ex/Em: 470/585. Fractions were measured for fluorescence using a fluorometer to determine the amount of doxorubicin that diffused across the sclera. After 24 hrs, cryosections of the sclera were obtained to visually identify the fluorescent doxorubicin in the tissue using an epifluorescent microscope.
NPDOX was able to diffuse across the sclera approximately ten times faster than DOX. The transscleral permeability rate, Ktrans, of DOX was: 1.77 ± 0.47 10-8 cm/sec compared to NPDOX at 1.71 ± 0.41 10-7 cm/sec. The cryosections of DOX showed saturation of DOX throughout the entire sclera, with greater intensity on the episcleral surface. Cryosections of NPDOX showed fluorescence concentrated in dots throughout the sclera instead of a broad saturation.
From these results, nanoparticles could serve as an effective vehicle/formulation to deliver doxorubicin transsclerally to treat intraocular tumors.
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