Curcumin/TGF-β1 siRNA loaded solid lipid nanoparticles alleviate cerebral injury after intracerebral hemorrhage by transnasal brain targeting

作者全名：Abudurexiti, Munire; Xue, Jun; Li, Xianzhe; Zhang, Xiaofeng; Qiu, Yongyi; Xiong, Senjie; Liu, Guojing; Yuan, Sangui; Tang, Rongrui

作者地址：[Abudurexiti, Munire; Zhang, Xiaofeng; Qiu, Yongyi; Xiong, Senjie; Liu, Guojing; Yuan, Sangui; Tang, Rongrui] Chongqing Med Univ, University Town Hosp, Dept Neurosurg, Chongqing, Peoples R China; [Xue, Jun] Chongqing Med Univ, Dept Neurosurg, Bishan Hosp, Chongqing, Peoples R China; [Abudurexiti, Munire; Li, Xianzhe] Southwest Minzu Univ, Coll Pharm, Chengdu 610041, Peoples R China

通信作者：Tang, RR (通讯作者)，Chongqing Med Univ, University Town Hosp, Dept Neurosurg, Chongqing, Peoples R China.

来源：COLLOIDS AND SURFACES B-BIOINTERFACES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001218114900001

JCR分区：Q1

影响因子：5.4

年份：2024

卷号：237

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Solid lipid nanoparticles; Targeted therapy; Anti-inflammatory; Curcumin; TGF-beta 1 siRNA

摘要：Intracerebral hemorrhage (ICH) is a prevalent cerebrovascular disorder. The inflammation induced by cerebral hemorrhage plays a crucial role in the secondary injury of ICH and often accompanied by a poor prognosis, leading to disease exacerbation. However, blood-brain barrier (BBB) limiting the penetration of therapeutic drugs to the brain. In this paper, our primary objective is to develop an innovative, non-invasive, safe, and targeted formulation. This novel approach aims to synergistically harness the combined therapeutic effects of drugs to intervene in inflammation via a non-injectable route, thereby significantly mitigating the secondary damage precipitated by inflammation following ICH. Thus, a novel "anti-inflammatory" cationic solid lipid nanoparticles (SLN) with targeting ability were constructed, which can enhance the stability of curcumin(CUR) and siRNA. We successfully developed SLN loaded with TGF-beta 1 siRNA and CUR (siRNA/CUR@SLN) that adhere to the requirements of drug delivery system by transnasal brain targeting. Through the characterization of nanoparticle properties, cytotoxicity assessment, in vitro pharmacological evaluation, and brain-targeting evaluation after nasal administration, siRNA/CUR@SLN exhibited a nearly spherical structure with a particle size of 125.0 +/- 1.93 nm, low cytotoxicity, high drug loading capacity, good sustained release function and good stability. In vitro anti-inflammatory results showcasing its remarkable anti-inflammatory activity. Moreover, in vivo pharmacological studies revealed that siRNA/CUR@SLN can be successfully delivered to brain tissue. Furthermore, it also elicited an effective anti-inflammatory response, alleviating brain inflammation. These results indicated that favorable brain-targeting ability and anti-inflammatory effects of siRNA/CUR@SLN in ICH model mice. In conclusion, our designed siRNA/CUR@SLN showed good brain targeting and anti-inflammatory effect ability after nasal administration, which lays the foundation for the treatment of inflammation caused by ICH and offers a novel approach for brain-targeted drug delivery and brings new hope.

基金机构：Research on the Prognostic Factors of Chronic Subdural Hematoma and Construction of a Machine Learning-based Prediction Model [KJQN20220045]

基金资助正文：This research was funded by the Research on the Prognostic Factors of Chronic Subdural Hematoma and Construction of a Machine Learning -based Prediction Model (Number: KJQN20220045) .