Exosome-inspired liposomal nanocarriers for precision methotrexate delivery in rheumatoid arthritis.

IF 4.7 4区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Targeting Pub Date : 2026-11-01 Epub Date: 2026-05-21 DOI:10.1080/1061186X.2026.2669792

Gaurav Tiwari, V Rao, Praveen Katiyar, Tora Shah, Manish R Bhise, Sekar Variavel, Pankaj Sharma

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引用次数: 0

Abstract

Rheumatoid arthritis (RA) is a progressive autoimmune disorder marked by synovial inflammation and cartilage erosion. Conventional methotrexate (MTX) therapy suffers from poor joint targeting and systemic toxicity. This study developed exosome-mimicking liposomes (EMLs) for precision MTX delivery. The optimised formulation (F8), as determined by a 3² factorial design, had vesicle size of 101.4 ± 2.3 nm, encapsulation efficiency (EE) of 82.6 ± 2.4% and a zeta potential of -30.7 ± 1.2 mV. For 24 h, EMLs gave a consistent release pattern (73.4%), matching the kinetics observed using the Korsmeyer-Peppas model (R² = 0.991). MTX taken up by cells was increased approximately 6-7 times higher than free MTX in RAW 264.7 cells. An in vivo study found that EMLs reached a C_max value of 9.6 ± 0.48 µg/mL, had an AUC_0-∞ of 54.3 ± 2.8 µg h/mL and showed 76.8% reduction in paw oedema in collagen-induced arthritis animals. Histopathology analysis found that joints were better protected and there was decreased inflammation and cartilage damage. The results show that EMLs are a reliable and biocompatible way to carry out safe, effective and targeted treatment of RA.

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类风湿性关节炎中精确甲氨蝶呤递送的外泌体启发脂质体纳米载体

类风湿性关节炎（RA）是一种以滑膜炎症和软骨侵蚀为特征的进行性自身免疫性疾病。传统的甲氨蝶呤（MTX）治疗存在关节靶向性差和全身毒性。本研究开发了用于MTX精确递送的外泌体模拟脂质体（EMLs）。经32因子设计确定，最佳配方（F8）的囊泡大小为101.4 ± 2.3 nm，包封效率（EE）为82.6 ± 2.4%，zeta电位为-30.7 ± 1.2 mV。在24 h内，EMLs的释放模式一致（73.4%），符合Korsmeyer-Peppas模型（R2 = 0.991）所观察到的动力学。在RAW 264.7细胞中，细胞摄取的MTX比游离的MTX增加了约6-7倍。一项体内研究发现，EMLs的Cmax值为9.6 ± 0.48 µg/mL， AUC0-∞为54.3 ± 2.8 µg h/mL，胶原诱导关节炎动物的足跖水肿减少76.8%。组织病理学分析发现，关节得到更好的保护，炎症和软骨损伤减少。结果表明，EMLs是一种可靠且具有生物相容性的方法，可安全、有效、靶向治疗类风湿关节炎。

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来源期刊

Journal of Drug Targeting 医学-药学

CiteScore

9.10

自引率

0.00%

发文量

165

审稿时长

2 months

期刊介绍： Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs. Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.