May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
t–PA encapsulation in liposomes for extravascular administration in venous thrombosis.
Author Affiliations & Notes
  • E.V. Christodoulakis
    Ophthalmology, Univ of Crete, Medical School, Heraklion, Crete, Greece
  • S.A. Antimisiaris
    Pharmacy, University of Patras, Patras, Greece
  • I.I. Naoumidi
    Ophthalmology, Univ of Crete, Medical School, Heraklion, Crete, Greece
  • V.A. Panteleontidis
    Ophthalmology, Univ of Crete, Medical School, Heraklion, Crete, Greece
  • D.I. X. Skondra
    Ophthalmology, Univ of Crete, Medical School, Heraklion, Crete, Greece
  • I.G. Pallikaris
    Ophthalmology, Univ of Crete, Medical School, Heraklion, Crete, Greece
  • M.K. Tsilimbaris
    Ophthalmology, Univ of Crete, Medical School, Heraklion, Crete, Greece
  • Footnotes
    Commercial Relationships  E.V. Christodoulakis, None; S.A. Antimisiaris, None; I.I. Naoumidi, None; V.A. Panteleontidis, None; D.I.X. Skondra, None; I.G. Pallikaris, None; M.K. Tsilimbaris, None.
  • Footnotes
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Investigative Ophthalmology & Visual Science May 2004, Vol.45, 5223. doi:https://doi.org/
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      E.V. Christodoulakis, S.A. Antimisiaris, I.I. Naoumidi, V.A. Panteleontidis, D.I. X. Skondra, I.G. Pallikaris, M.K. Tsilimbaris; t–PA encapsulation in liposomes for extravascular administration in venous thrombosis. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5223. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Intravitreal injection of tPA has been used for thrombolysis in retinal vein occlusion with controversial results. We evaluated the thrombolytic action of a t–PA preparation encapsulated in liposomes using a novel encapsulation technique. The encapsulated t–PA preparation was assessed in vitro and by means of an animal model of vein thrombosis. Methods: tPA was encapsulated in liposomes prepared by the DRV (dried–reconstituted vesicle) method. For the measurement of t–PA encapsulated in liposomes, a serine protease specific substrate (S–2288, by Chromogenics, Milano, IT) was utilized. Thrombolytic activity of encapsulated t–PA was evaluated in vitro. An animal model (vein photothrombosis in rabbit ear) was used for the evaluation of transmural thrombolitic activity of liposomes–encapsulated t–PA. Results: t–PA encapsulation was found to be increased when lower t–PA / lipid molar ratios, were used during liposome preparation. When low t–PA/lipid molar ratios were used (0.14 x 10–3 – 0.28 x 10–3) the resulting encapsulation of t–PA was 11.2 [[Unable to Display Character: ]] 2.1 %. Encapsulated t–PA was found thrombolytically active in vitro. The preliminary histological results of our animal studies indicate that liposomes–encapsulated t–PA may show thrombolytic activity when administered subcutaneously next to the photothrombosed vessel, while free, uncapsulated t–PA does not have such an activity. Conclusions: Encapsulation of t–PA in liposomes may increase permeability of t–PA through the vascular lumen and facilitate thrombolysis when the drug is given extravascularly.

Keywords: retina • vascular occlusion/vascular occlusive disease • pharmacology 
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