Human serum albumin-based nanoparticles alter raloxifene administration and improve bioavailability

• Published in: Drug delivery Vol. 29; no. 1; pp. 2685 - 2693
• Main Authors: Yang, Shu-Jyuan, Chang, Chih-Hao, Young, Tai-Horng, Wang, Chung-Hao, Tseng, Tzu-Hao, Wang, Man-Ling
• Format: Journal Article
• Language: English
• Published: Philadelphia Taylor & Francis 31.12.2022; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Bioavailability; Estrogens; human serum albumin; nanoparticle; Nanoparticles; Osteoporosis; poly(sodium styrene sulfonate); raloxifene
• ISSN: 1071-7544; 1521-0464
• 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. In vitro 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.