Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
Department of Orthopedics, National Taiwan University Hospital Jin-Shan Branch, New Taipei City, Taiwan.
Drug Deliv. 2022 Dec;29(1):2685-2693. doi: 10.1080/10717544.2022.2111479.
Osteoporosis is a disease that reduces bone mass and microarchitecture, which makes bones fragile. Postmenopausal osteoporosis occurs due to estrogen deficiency. Raloxifene is a selective estrogen receptor modulator used to treat postmenopausal osteoporosis. However, it has a low bioavailability, which requires long-term, high-dose raloxifene administration to be effective and causes several side effects. Herein, raloxifene was encapsulated in human serum albumin (HSA)-based nanoparticles (Ral/HSA/PSS NPs) as an intravenous-injection pharmaceutical formulation to increase its bioavailability and reduce the treatment dosage and time. results indicated that raloxifene molecules were well distributed in HSA-based nanoparticles as an amorphous state, and the resulting raloxifene formulation was stabile during long-term storage duration. The Ral/HSA/PSS NPs were both biocompatible and hemocompatible with a decreased cytotoxicity of high-dose raloxifene. Moreover, the intravenous administration of the prepared Ral/HSA/PSS NPs to rats improved raloxifene bioavailability and improved its half-life in plasma. These raloxifene-loaded nanoparticles may be a potential nanomedicine candidate for treating postmenopausal osteoporosis with lower raloxifene dosages.
骨质疏松症是一种降低骨量和微结构的疾病，使骨骼脆弱。绝经后骨质疏松症是由于雌激素缺乏引起的。雷洛昔芬是一种选择性雌激素受体调节剂，用于治疗绝经后骨质疏松症。然而，它的生物利用度较低，需要长期、高剂量的雷洛昔芬给药才能有效，并引起几种副作用。在此，雷洛昔芬被包裹在人血清白蛋白（HSA）-基于纳米粒子（Ral/HSA/PSS NPs）中作为静脉注射药物制剂，以提高其生物利用度并降低治疗剂量和时间。结果表明，雷洛昔芬分子在 HSA 基纳米粒子中呈无定形态均匀分布，所得雷洛昔芬制剂在长期储存期间稳定。Ral/HSA/PSS NPs 具有良好的生物相容性和血液相容性，降低了高剂量雷洛昔芬的细胞毒性。此外，将制备的 Ral/HSA/PSS NPs 静脉注射到大鼠体内，提高了雷洛昔芬的生物利用度，并延长了其在血浆中的半衰期。这些载有雷洛昔芬的纳米粒子可能是一种具有较低雷洛昔芬剂量治疗绝经后骨质疏松症的潜在纳米医学候选药物。
