Strontium Ranelate

By 2050, the global aging population is predicted to reach 1.5 billion, highlighting the need to enhance the quality of life of the elderly population. Osteoporotic fractures are projected to affect one in three women and one in five men over age 50. Initial treatments for osteoporosis in postmenopausal women include antiresorptive agents such as bisphosphonates, strontium ranelate, estrogen replacement therapy (ERT) and selective estrogen receptor modulators (SERMs). However, these do not rebuild bone, limiting their effectiveness. Denosumab, an FDA-approved antiresorptive monoclonal antibody, also has drawbacks including high costs, biannual subcutaneous injections, slow healing, impaired bone growth and side effects like eczema, flatulence, cellulitis, osteonecrosis of the jaw (ONJ) and an increased risk of spinal fractures after discontinuation of treatment. Nutraceuticals, particularly phytoestrogens, are gaining attention for their health benefits and safety in osteoporosis prevention, management and treatment. Phytoestrogens are plant metabolites similar to mammalian estrogens and include isoflavones, coumestans, lignans, stilbenes, and flavonoids. They interact with estrogen receptor isoforms ERα and ERβ, acting as agonists or antagonists based on concentration and bioavailability. Their tissue-selective activities are particularly significant: anti-estrogenic effects in reproductive tissues may lower the risk of hormone-related cancers (such as ovarian, uterine, breast and prostate), while estrogenic effects on bone could contribute to the preservation of bone mineral density.Phytoestrogens are, thus, used in managing breast and prostate cancers, cardiovascular diseases, menopause and osteoporosis. The present review focuses on the botanical origin, classification, sources and mechanism(s) of action of major phytoestrogens, their potential in prevention and management of osteoporosis and the requirement for additional clinical trials to achieve more definitive outcomes in order to confirm their efficacy and dosage safety.

Strontium ranelate (SR) is an effective bone regeneration drug; however, its low bioavailability and strong hydrophilicity cause a strong cytotoxicity, venous thrombosis, and allergic reactions when administered in its free form. This study aims to enhance the SR bioavailability by utilizing nanostructured lipid carriers (NLC) as a drug delivery system (DDS).

To improve the drug delivery efficiency and sustained release of the NLC, their surfaces were coated with chitosan oligosaccharide (COS), a natural polymer. The synthesis of COS-NLC was confirmed by measuring particle size and zeta potential, while surface morphology was evaluated using atomic force microscopy (AFM). SR loading efficiencies and release profiles were analyzed via reversed-phase high-performance liquid chromatography (RP-HPLC), and cytotoxicity was evaluated in mouse fibroblast L929 cells.

Particle characterization indicated that the COS coating slightly increased the particle size (i.e., from 128.99 ± 2.77 to 131.46 ± 2.13 nm) and zeta potential (i.e., from - 13.94 ± 0.49 to - 6.58 ± 0.32 mV) of the NLC. The COS-NLC exhibited a high SR-loading efficiency of ~ 86.31 ± 3.28%. An in vitro release test demonstrated an improved sustained release tendency of SR from the COS-NLC compared to that from the uncoated NLC. In cytotoxicity assays using L929 cells, the COS coating reduced the cytotoxicity of the formulated DDS, and the SR-COS-NLC exhibited a 1.4-fold higher cell regeneration effect than SR alone.

These findings suggest that the developed COS-NLC serve as an effective and biocompatible DDS platform for the delivery of poorly bioavailable drugs.