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用于靶向溃疡性结肠炎治疗的载氯诺昔康新型脂质体的制剂、优化及评价:体内外研究

Formulation, optimisation, and evaluation of Lornoxicam-loaded Novasomes for targeted ulcerative colitis therapy: in vitro and in vivo investigations.

作者信息

Darwish Asmaa Badawy, Salama Abeer, Essam Ibrahim Al-Samadi Inas

机构信息

Pharmaceutical Technology Department, National Research Centre, Cairo, Egypt.

Pharmacology Department, National Research Centre, Cairo, Egypt.

出版信息

J Drug Target. 2025 Jul;33(6):975-988. doi: 10.1080/1061186X.2025.2456929. Epub 2025 Jan 25.

Abstract

The purpose of this work was to create and assess Lornoxicam (LOR) loaded Novasomes (Novas) for the efficient treatment of ulcerative colitis. The study was performed using a 2 factorial design to investigate the impact of several formulation variables. Three separate parameters were investigated: Surface Active agent (SAA) type (), LOR concentration (), and SAA: Oleic acid ratio (). The dependent responses included encapsulation efficiency (: EE %), particle size (: PS), zeta potential (: ZP), and polydispersity index (: PDI). The vesicles demonstrated remarkable LOR encapsulation efficiency, ranging from 81.32 ± 3.24 to 98.64 ± 0.99%. The vesicle sizes ranged from 329 ± 9.88 to 583.4 ± 9.04 nm with high negative zeta potential values. The release pattern for Novas' LOR was biphasic and adhered to Higuchi's model. An in-vivo study assessed how LOR-Novas affected rats' acetic acid-induced ulcerative colitis (UC). The optimised LOR-Novas effectively reduced colonic ulceration ( < 0.05) and reduced the inflammatory pathway inhibiting Toll-like receptor 4 (TLR4), Nuclear factor kappa β (NF-κβ) and inducible nitric oxide (iNO). At the same time, it elevated Silent information regulator-1(SIRT-1) and reduced glutathione (GSH) colon contents. Thus, the current study suggested that the formulation of LOR-Novas may be a viable treatment for ulcerative colitis.

摘要

本研究旨在制备并评估载有氯诺昔康(LOR)的新型脂质体(Novas)用于溃疡性结肠炎的有效治疗。本研究采用二因素设计来研究几种制剂变量的影响。研究了三个独立参数:表面活性剂(SAA)类型()、LOR浓度()和SAA:油酸比例()。相关响应指标包括包封率(:EE%)、粒径(:PS)、zeta电位(:ZP)和多分散指数(:PDI)。这些囊泡表现出显著的LOR包封率,范围为81.32±3.24%至98.64±0.99%。囊泡大小范围为329±9.88至583.4±9.04nm,zeta电位值为高负值。Novas的LOR释放模式为双相,符合Higuchi模型。一项体内研究评估了LOR-Novas对大鼠乙酸诱导的溃疡性结肠炎(UC)的影响。优化后的LOR-Novas有效减轻了结肠溃疡(<0.05),并减少了炎症途径,抑制了Toll样受体4(TLR4)、核因子κβ(NF-κβ)和诱导型一氧化氮(iNO)。同时,它提高了沉默信息调节因子-1(SIRT-1)并降低了结肠内容物中的谷胱甘肽(GSH)。因此,本研究表明LOR-Novas制剂可能是溃疡性结肠炎的一种可行治疗方法。

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