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Arie Reijerkerk, Chantal C Appeldoorn, Jaap Rip, Marco de Boer, Pieter Gaillard; Systemic treatment with glutathione PEGylated liposomal methylprednisolone (2B3-201) improves therapeutic efficacy in a model of ocular inflammation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2859.
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Ocular inflammation is associated with the loss of visual acuity and subsequent blindness. Since their development, glucocorticoids have been the mainstay of therapy for ocular inflammatory diseases. However, the clinical benefit is limited by side effects due to the chronic use and generally high dosage, which is required for effective treatment. We have developed the G-Technology® to provide a means for sustained drug delivery, increased drug half-life, and reduced bodily drug exposure. 2B3-201, glutathione PEGylated liposomal methylprednisolone, has been developed as treatment for neuroinflammatory conditions and was evaluated in ocular inflammation.
The efficacy of 2B3-201 was investigated in rats with experimental autoimmune uveitis (EAU). Rats received 10 mg/kg of 2B3-201 intravenously at disease onset and at peak of the disease. The same dose of free methylprednisolone served as control treatment. Clinical signs of ocular inflammation were assessed by slit lamp and immunohistochemistry.
Whereas free methylprednisolone was ineffective, two doses of 2B3-201 almost completely abolished clinical signs of EAU. This was further corroborated by immunohistochemical analyses of isolated eyes. 2B3-201 significantly reduced the infiltration of inflammatory cells and subsequent destruction of the retina cell layers.
In this study we are the first to show that systemic treatment with 2B3-201, a glutathione PEGylated liposomal methylprednisolone formulation, resulted in a superior efficacy in rats with EAU. Altogether, our findings hold promise for the development of a safe and more convenient systemic treatment for uveitis.
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