Background/Objectives: The limited targeting efficiency and systemic toxicity of conventional medicine present significant challenges in the treatment of skeletal disorders, such as bone tuberculosis. To address these limitations, we developed a bone-targeting nanomicelle delivery system functionalized with alendronate (ALN), designated ALN-PLGA-mPEG@RPT, to improve the targeted delivery and therapeutic efficacy of rifapentine (RPT) in bone tissue. Methods: The ALN-PLGA-mPEG blank micelles, prepared in accordance with our research group’s optimized protocol, were loaded with RPT and subjected to systematic formulation optimization. The resulting nanomicellar system was comprehensively characterized in terms of its physicochemical properties, including particle size and polydispersity index (PDI). Additionally, drug-loading capacity, encapsulation efficiency, and in vitro release curve were evaluated. Bone-targeting efficacy was assessed using in vivo imaging techniques, while biodistribution and safety profiles were determined through in vivo distribution studies and histopathological examination. Results: The optimized ALN-PLGA-mPEG@RPT nanomicelles exhibited a mean particle size of 101.90 ± 4.17 nm, and a PDI of 0.242 ± 0.021. The formulation achieved a drug loading of 16.74 ± 0.51% with an encapsulation efficiency of 50.27 ± 1.91%. In vitro release studies confirmed a sustained-release profile, with only 25% of RPT released within 12 h. In vivo imaging revealed significantly enhanced bone-targeting capability in the ALN-modified group, showing a 1.93-fold higher drug accumulation in bone tissue compared to blood. Histopathological analysis indicated no observable pathological alterations in major organs. Conclusions: The ALN-PLGA-mPEG@RPT nanomicelle system exhibits favorable bone-targeting efficiency, sustained-release properties, and biocompatibility, representing a promising strategy for the precise treatment of bone tuberculosis and other skeletal diseases.
Wang et al. (Thu,) studied this question.