Combined Nanoparticle-Based Delivery of Estrogens and Raloxifen in Postmenopausal Osteoporosis

Osteoporosis (OP) is a common chronic disease that significantly increases the risk of bone fractures. Pharmacotherapy uses, among others, 17beta-estradiol (E2), which has been replaced in recent years by raloxifene hydrochloride (RLX). The need for long-term, high-dose therapy with these drugs is associated with serious adverse effects. The aim of this review is to analyze the current state of knowledge over the last 5 years (2020-2025) regarding the use of nanoparticles (NPs) in the delivery of E2 and RLX, with particular emphasis on their impact on bioavailability, pharmacokinetic profile, reduction in adverse effects, and improvement in the effectiveness of postmenopausal osteoporosis therapy. Preclinical studies show that combining E2 or RLX with various types of NPs reduces cytotoxicity, improves pharmacokinetic parameters, and enhances the therapeutic effects of drugs used in postmenopausal osteoporosis. These effects are mainly attributed to improved pharmacokinetics and controlled drug release, rather than confirmed active tissue targeting. However, these findings are based on preclinical models and require further validation in clinical studies. The analysis concludes that while NP systems significantly enhance the pharmacokinetic profile and safety of E2 and RLX in preclinical models, claims of true bone-specific targeting remain largely unsubstantiated, highlighting a key area for future research.