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Intrastriatal Injection of Autologous Blood or Clostridial Collagenase as Murine Models of Intracerebral Hemorrhage
Published on: July 3, 2014
Curcumin/TGF-β1 siRNA loaded solid lipid nanoparticles alleviate cerebral injury after intracerebral hemorrhage by
Munire Abudurexiti1, Jun Xue2, Xianzhe Li3
1Department of Neurosurgery, University-Town Hospital of Chongqing Medical University, Chongqing, China; College of Pharmacy, Southwest Minzu University, Chendu 610041, China.
Insights
This study developed novel solid lipid nanoparticles (SLN) for transnasal delivery of curcumin and siRNA to treat brain inflammation after intracerebral hemorrhage (ICH). The targeted SLN demonstrated effective anti-inflammatory effects and brain delivery, offering a new therapeutic approach.
Area of Science:
- Neuroscience
- Biotechnology
- Pharmacology
Background:
- Intracerebral hemorrhage (ICH) causes secondary brain injury through inflammation.
- The blood-brain barrier (BBB) restricts drug delivery to the brain.
- Current treatments for ICH-induced inflammation are limited by poor drug penetration.
Purpose of the Study:
- To develop a novel, non-invasive, targeted drug delivery system for treating ICH-induced inflammation.
- To create "anti-inflammatory" cationic solid lipid nanoparticles (SLN) for enhanced stability and brain targeting.
- To evaluate the synergistic therapeutic effects of curcumin (CUR) and TGF-β1 siRNA delivered via SLN.
Main Methods:
- Construction of cationic solid lipid nanoparticles (SLN) loaded with curcumin (CUR) and TGF-β1 siRNA (siRNA/CUR@SLN).
- Characterization of nanoparticle properties (size, morphology, stability, drug loading, sustained release).
- In vitro and in vivo evaluation of anti-inflammatory activity and brain targeting after nasal administration in ICH model mice.
Main Results:
- siRNA/CUR@SLN exhibited optimal physicochemical properties: spherical shape, 125 nm size, low cytotoxicity, high drug loading, good stability, and sustained release.
- In vitro studies confirmed significant anti-inflammatory activity.
- In vivo studies demonstrated successful brain targeting via nasal administration and effective alleviation of brain inflammation in ICH mice.
Conclusions:
- The designed siRNA/CUR@SLN formulation shows excellent brain-targeting ability and potent anti-inflammatory effects following nasal administration.
- This novel approach provides a promising strategy for treating inflammation associated with ICH.
- The study offers a new avenue for non-invasive, targeted brain drug delivery, addressing a critical unmet need in ICH treatment.
Abstract:
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-β1 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.
