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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.

DOI:10.1080/1061186X.2025.2456929
PMID:39831638
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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