ArticleMedical science monitor basic research2025
Enhanced Tumor Targeting with Midazolam-Loaded PLGA Nanoparticles: An In Vivo Analysis of Safety and Efficacy.
Article in Medical science monitor basic research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND Midazolam, a commonly used sedative, faces challenges in cancer therapy due to its central nervous system (CNS) toxicity and suboptimal targeting of tumor sites. This study explores the use of poly (lactic-co-glycolic acid) (PLGA) nanoparticles to enhance the delivery of Midazolam, aiming to improve antitumor efficacy while minimizing CNS toxicity. MATERIAL AND METHODS We developed Midazolam-loaded PLGA nanoparticles (Midazolam PLGA NPs) using the ultrasonic emulsification-solvent evaporation technique. These nanoparticles were thoroughly characterized for particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, drug loading, and stability. We assessed cellular uptake and cytotoxicity via the MTT assay, while organ accumulation was quantified using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The safety profile was evaluated by monitoring body weight changes in A549 tumor-bearing mice. RESULTS The Midazolam PLGA nanoparticles exhibited a spherical shape, uniform size, high encapsulation efficiency, and excellent colloidal stability. In vitro release studies indicated that 62.51% of Midazolam was released within 24 hours. Enhanced cellular uptake was noted for the nanoparticles in comparison to the solution, with significant accumulation at tumor sites and increased free drug release. The nanoparticles effectively killed tumor cells while sparing normal tissues, demonstrating superior antitumor activity compared to the Midazolam solution. Importantly, treated mice maintained stable body weight, suggesting a favorable safety profile. CONCLUSIONS Midazolam-loaded PLGA nanoparticles present a promising approach for targeted cancer therapy. They enhance encapsulation, stability, and selective tumor cell cytotoxicity, resulting in greater antitumor efficacy with minimal adverse effects compared to conventional Midazolam solutions.
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