ArticlePharmaceutical research2026
REAL208, a Liposome-based Formulation of Phosphodiesterase Inhibitor, Protects Acute Kidney Deficiency in Mice.
Article in Pharmaceutical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveAcute kidney injury (AKI) is a life-threatening condition characterized by inflammation, oxidative stress, and tubular cell apoptosis for which no specific pharmacological therapy currently exists. Dipyridamole, a phosphodiesterase inhibitor with antiplatelet, anti-inflammatory, and cytoprotective properties, has shown renoprotective potential; however, its clinical use in AKI is limited by pharmacokinetic constraints. METHODS AND
resultsTo address this issue, we developed REAL208, a liposome-encapsulated dipyridamole formulation and evaluated its safety and therapeutic efficacy in experimental AKI models. Safety testing in C57BL/6 mice demonstrated that REAL208 was well tolerated at doses up to 50 mg/kg, without evidence of hepatic or renal toxicity. In lipopolysaccharide (LPS)- and ischemia/reperfusion (I/R)-induced AKI models, intravenous administration of REAL208 (2.5-10 mg/kg) significantly improved survival, reduced serum blood urea nitrogen and creatinine levels, and restored glomerular filtration rate compared to that observed in the untreated controls. Histological analyses revealed preserved tubular architecture, reduced neutrophil and macrophage infiltration, and modulation of the expression of injury markers, including KIM-1 and PPARγ. Immunohistochemistry further showed attenuation of Nrf2 and HO-1 upregulation, indicating suppression of oxidative stress. In vitro, REAL208 protected HK-2 proximal tubular cells against LPS- or hypoxia/reperfusion-induced injury, maintained mitochondrial membrane potential, enhanced oxygen consumption rates, and reduced inflammatory signaling (nuclear p65 and Bcl-2).
conclusionsThese findings demonstrated that liposomal dipyridamole exerts robust renoprotective effects by preserving mitochondrial function, suppressing oxidative stress, and attenuating inflammation. REAL208 represents a promising therapeutic strategy for AKI and warrants further translational and clinical investigations.
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