Enhancing the Solubility and Oral Bioavailability of Trimethoprim Through PEG-PLGA Nanoparticles: A Comprehensive Evaluation of In Vitro and In Vivo Performance

文献类型： 外文期刊

第一作者： Zhou, Yaxin

作者： Zhou, Yaxin;Dai, Guonian;Xu, Jing;Li, Bing;Zhang, Jiyu;Zhou, Yaxin;Dai, Guonian;Xu, Jing;Li, Bing;Zhang, Jiyu;Zhou, Yaxin;Dai, Guonian;Xu, Jing;Li, Bing;Zhang, Jiyu;Zhou, Yaxin;Chen, Shulin;Xu, Weibing

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关键词： trimethoprim; PEG-PLGA; nanoparticles; bioavailability; pharmacokinetics

期刊名称：PHARMACEUTICS （ 影响因子：5.5； 五年影响因子：5.8 ）

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年卷期： 2025 年 17 卷 8 期

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收录情况： SCI

摘要： Background/Objectives: Trimethoprim (TMP), a sulfonamide antibacterial synergist, is widely used in antimicrobial therapy owing to its broad-spectrum activity and clinical efficacy in treating respiratory, urinary tract, and gastrointestinal infections. However, its application is limited due to poor aqueous solubility, a short elimination half-life (t1/2), and low bioavailability. In this study, we proposed TMP loaded by PEG-PLGA polymer nanoparticles (NPs) to increase its efficacy. Methods: We synthesized and thoroughly characterized PEG-PLGA NPs loaded with TMP using an oil-in-water (O/W) emulsion solvent evaporation method, denoted as PEG-PLGA/TMP NPs. Drug loading capacity (LC) and encapsulation efficiency (EE) were quantified by ultra-performance liquid chromatography (UPLC). Comprehensive investigations were conducted on the stability of PEG-PLGA/TMP NPs, in vitro drug release profiles, and in vivo pharmacokinetics. Results: The optimized PEG-PLGA/TMP NPs displayed a high LC of 34.0 +/- 1.6%, a particle size of 245 +/- 40 nm, a polydispersity index (PDI) of 0.103 +/- 0.019, a zeta potential of -23.8 +/- 1.2 mV, and an EE of 88.2 +/- 4.3%. The NPs remained stable at 4 degrees C for 30 days and under acidic conditions. In vitro release showed sustained biphasic kinetics and enhanced cumulative release, 86% at pH 6.8, aligning with first-order models. Pharmacokinetics in rats revealed a 2.82-fold bioavailability increase, prolonged half-life 2.47 +/- 0.19 h versus 0.72 +/- 0.08 h for free TMP, and extended MRT 3.10 +/- 0.11 h versus 1.27 +/- 0.11 h. Conclusions: PEG-PLGA NPs enhanced the solubility and oral bioavailability of TMP via high drug loading, stability, and sustained-release kinetics, validated by robust in vitro-in vivo correlation, offering a promising alternative for clinical antimicrobial therapy.

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