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Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes
Published on: July 23, 2016
Engineered liposomes targeting the gut-CNS Axis for comprehensive therapy of spinal cord injury
Xue Wang1, Jin Wu2, Xinlong Liu1
1Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China.
Abstract:
Effective curative therapies for spinal cord injury (SCI), which is often accompanied by intestinal complications, are lacking. Potential therapeutic targets include astrocytes and their enteric nervous system counterpart, enteric glial cells (EGCs). Based on shared biomarkers and similar functions of both cell types, we designed an orally administered targeted delivery system in which the neuropeptide apamin, stabilized by sulfur replacement with selenium, was adopted as a targeting moiety, and the liposome surface was protected with a non-covalent cross-linked chitosan oligosaccharide lactate layer. The system effectively permeated through oral absorption barriers, targeted local EGCs and astrocytes after systemic circulation, allowing for comprehensive SCI therapy. Given the involvement of the gut-organ axis in a growing number of diseases, our research may shed light on new aspects of the oral administration route as a bypass for multiple interventions and targeted therapy.
Insights
This study introduces an oral drug delivery system targeting glial cells for spinal cord injury (SCI) therapy. The novel system effectively reaches and treats both astrocytes and enteric glial cells (EGCs) for comprehensive spinal cord injury recovery.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Pharmacology
Background:
- Spinal cord injury (SCI) lacks effective curative therapies, often leading to intestinal complications.
- Astrocytes and enteric glial cells (EGCs) are identified as potential therapeutic targets due to shared functions.
- The gut-organ axis plays a crucial role in various diseases, highlighting the importance of gut-targeted therapies.
Purpose of the Study:
- To design and evaluate an orally administered targeted delivery system for spinal cord injury (SCI) therapy.
- To utilize apamin as a targeting moiety and a chitosan oligosaccharide lactate layer for enhanced delivery.
- To investigate the system's ability to target astrocytes and enteric glial cells (EGCs) for comprehensive SCI treatment.
Main Methods:
- Development of an orally administered liposomal system.
- Stabilization of neuropeptide apamin with selenium for targeting.
- Protection of the liposome surface with a cross-linked chitosan oligosaccharide lactate layer.
- Evaluation of oral absorption barriers penetration and targeted delivery to EGCs and astrocytes.
Main Results:
- The designed system successfully permeated oral absorption barriers.
- The system effectively targeted local enteric glial cells (EGCs) and astrocytes after systemic circulation.
- Demonstrated potential for comprehensive spinal cord injury (SCI) therapy.
Conclusions:
- An orally administered targeted delivery system shows promise for spinal cord injury (SCI) treatment.
- This approach offers a novel strategy for targeting glial cells via the gut-organ axis.
- Oral administration may serve as a viable bypass for multiple interventions and targeted therapies in SCI.
