Nano-lanthanum hydroxide, a novel phosphate binder, for treating hyperphosphatemia: A preclinical study
This study is to determine the pharmacological effects of nano-lanthanum hydroxide (nano-LH) in the treatment of hyperphosphatemia, in comparison with other phosphate binders. Rat models of chronic renal failure and hyperphosphatemia were induced by adenine, which were treated with nano-LH (0.15, 0.10, and 0.05 g/Kg/d), lanthanum carbonate (0.30 g/Kg/d), and normal-size lanthanum hydroxide (0.10 g/Kg/d), respectively. To investigate the therapeutic effects, the serum levels of phosphorus, Scr, Ucr, BUN, UUN, PTH, and other hyperphosphatemia-related biochemical indicators were determined. A novel phosphorus-binding agent, nano-LH, was synthesized herein, which was rod-like particle with the length of 30–50 nm, width of 10–20 nm, and diameter of 5–10 nm. In vitro phosphorus binding experiments showed that nano-LH had better binding rate. Pharmacodynamic experiments confirmed that the therapeutic effects of lanthanum-hydroxide (0.10 g/kg/d) were superior to other existing phosphate binders in rat models of hyperphosphatemia, in lowering the blood phosphate level and improving the renal function. In the term of drug safety, our preliminary results showed that the nano-LH at appropriate dose did not cause death cases in mice, and the serum levels of alkaline phosphatase and lactate dehydrogenase were not significantly changed, indicating good oral safety. Nano-LH has high potency compared with several phosphate binders, which might be a promising therapeutic agent for the treatment of hyperphosphatemia in clinic.
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