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采用 2 全因子设计评估塞来昔布囊泡双分子层用于治疗脂多糖诱导的阿尔茨海默病的神经保护效率。

Neuroprotective efficiency of celecoxib vesicular bilosomes for the management of lipopolysaccharide-induced Alzheimer in mice employing 2 full factorial design.

机构信息

Pharmaceutical Technology Department, National Research Centre, 33 El-Buhouth Street, Dokki, Cairo, 12622, Egypt.

Pharmacology Department, National Research Centre, 33 El-Buhouth Street, Dokki, Cairo, 12622, Egypt.

出版信息

Inflammopharmacology. 2024 Dec;32(6):3925-3942. doi: 10.1007/s10787-024-01522-y. Epub 2024 Jul 17.

Abstract

The aim of this study was to develop and evaluate bilosomes loaded with Celecoxib (CXB) for the efficient treatment of Alzheimer. The thin-film hydration approach was utilized in the formulation of CXB bilosomes (CXB-BLs). The study used a 2-factorial design to investigate the impact of several formulation variables. Three separate parameters were investigated: bile salt type (X), medication amount (X), and lipid-bile salt ratio (X). The dependent responses included entrapment efficiency (Y: EE %), particle size (Y: PS), and zeta potential (: ZP). The formulation factors were statistically optimized using the Design-Expert program. The vesicles demonstrated remarkable CXB encapsulation efficiency, ranging from 94.16 ± 1.91 to 98.38 ± 0.85%. The vesicle sizes ranged from 241.8 ± 6.74 to 352 ± 2.34 nm. The produced formulations have high negative zeta potential values, indicating strong stability. Transmission electron microscopy (TEM) revealed that the optimized vesicles had a spherical form. CXB release from BLs was biphasic, with the release pattern following Higuchi's model. In vivo studies confirmed the efficiency of CXB-BLs in management of lipopolysaccharide-induced Alzheimer as CXB-BLs ameliorated cognitive dysfunction, decreased acetylcholinesterase (AChE), and inhibited neuro-inflammation and neuro-degeneration through reducing Toll-like receptor (TLR4), and Interleukin-1β (IL-1β) levels. The findings suggested that the created CXB-BLs could be a potential drug delivery strategy for Alzheimer's treatment.

摘要

本研究旨在开发并评估载有塞来昔布(CXB)的双分子层囊泡用于阿尔茨海默病的有效治疗。采用薄膜水化法制备 CXB 双分子层囊泡(CXB-BLs)。该研究采用 2 因素设计考察了多个制剂变量的影响。考察了三个独立参数:胆汁盐类型(X)、药物剂量(X)和脂质-胆汁盐比例(X)。依赖响应包括包封效率(Y:EE%)、粒径(Y:PS)和 Zeta 电位(Z:ZP)。使用 Design-Expert 程序对制剂因素进行了统计学优化。囊泡表现出显著的 CXB 包封效率,范围为 94.16±1.91%至 98.38±0.85%。囊泡大小范围为 241.8±6.74nm 至 352±2.34nm。所制备的制剂具有高的负 Zeta 电位值,表明具有强稳定性。透射电子显微镜(TEM)显示优化后的囊泡呈球形。CXB 从 BLs 的释放呈双相,释放模式符合 Higuchi 模型。体内研究证实 CXB-BLs 在管理脂多糖诱导的阿尔茨海默病中的有效性,因为 CXB-BLs 通过降低 Toll 样受体(TLR4)和白细胞介素-1β(IL-1β)水平改善认知功能障碍,降低乙酰胆碱酯酶(AChE),抑制神经炎症和神经变性。研究结果表明,所构建的 CXB-BLs 可能是治疗阿尔茨海默病的一种有潜力的药物传递策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ab9/11550292/e9e4d75cdaaf/10787_2024_1522_Fig1_HTML.jpg

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