Currently approved therapies for age-related macular degeneration (AMD) are inhibitors against vascular endothelial growth factor (VEGF), which is a major contributor to the pathogenesis of neovascular AMD (nAMD). Intravitreal injections of anti-VEGF drugs have shown dramatic visual benefits for AMD patients. However, a significant portion of AMD patients exhibit an incomplete response to therapy and, over the extended management course, can lose vision, with the formation of submacular fibrosis as one risk factor. We investigated a novel target for AMD treatments, fibroblast growth factor 2 (FGF2), which has been implicated in the pathophysiology of both angiogenesis and fibrosis in a variety of tissue and organ systems. The anti-FGF2 aptamer, RBM-007, was examined for treatment of nAMD in animal models. In
in vivo
studies conducted in mice and rats, RBM-007 was able to inhibit FGF2-induced angiogenesis, laser-induced choroidal neovascularization (CNV), and CNV with fibrosis. Pharmacokinetic studies of RBM-007 in the rabbit vitreous revealed high and relatively long-lasting profiles that are superior to other approved anti-VEGF drugs. The anti-angiogenic and anti-scarring dual action of RBM-007 holds promise as an additive or alternative therapy to anti-VEGF treatments for nAMD.
Poor penetration of diclofenac through in vitro rat dorsal skin including subcutaneous tissue was observed. The poor penetration of diclofenac seemed to be predominIntly due to the poor permeability of the stratum corneum. Hydrogenated soya phospholipids (phospholipid) in aqueous gel form increased the penetration of diclofenac in the in vitro study, by increasing diclofenac transport through the stratum corneum. In the in vivo percutaneous absorption of diclofenac, the presence of phospholipid in aqueous gel form increased both plasma diclofenac concentration and diclofenac accumulation in the dorsal skin tissue, including subcutaneous tissue. Since a marked accumulation of diclofenac in the subcutaneous tissue after application of the aqueous gel was observed both in vivo and in vitro, percutaneous application of diclofenac in the aqueous gel form, prepared with phospholipid, may be available for topical treatment rather than for systemic treatment.
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