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The affinity of lipid-coated microbubbles to maturing spinal cord injury sites
I U Kureshi1, S Y Ho, H C Onyiuke
1Department of Surgery, University of Connecticut Health Center, Farmington, USA.
Objective:
This laboratory has demonstrated that lipid-coated microbubbles (LCMs) effectively aggregate and deliver chemotherapeutic drugs into rat brain tumor cells and antigliosis agents into maturing rat brain injury sites. In this study, we report the affinity of tail vein-injected LCMs to the injured rat spinal cord by a compressive lesion to the upper thoracic region.
Methods:
The accumulation of LCMs in the injured spinal cord was analyzed by labeling it with a lipid-soluble fluorescent dye, 3,3'-dioctadecyloxacarbocyanine perchlorate. Indices of glial fibrillary acidic protein were measured concomitantly with 3,3'-dioctadecyloxacarbocyanine perchlorate-labeled LCMs using confocal microscopy.
Results:
There was no aggregation of LCMs accumulated 1 and 6 hours after injury; however, when given 2, 4, and 7 days after injury, LCMs showed a clear affinity for the injured region. LCM aggregation shifted from the central necrotic area of the injury on postinjury Day 2 and postinjury Day 4 to the white matter among glial fibrillary acidic protein-positive astrocytes by postinjury Day 7.
Conclusion:
Affinity of LCMs for spinal cord injury sites may be mediated in the early stages after injury by proliferating macrophages in the necrotic center, and then in later stages by glial fibrillary acidic protein-positive astrocytes in adjacent white matter. These findings suggest a potential for using LCMs as a delivery vehicle to concentrate lipid-soluble agents in spinal cord injury sites.
Insights
Lipid-coated microbubbles (LCMs) show affinity for injured rat spinal cords, accumulating in damaged areas days after injury. This suggests LCMs could deliver therapeutic agents to spinal cord injury sites.
Area of Science:
- Biomedical Engineering
- Neuroscience
- Drug Delivery Systems
Background:
- Lipid-coated microbubbles (LCMs) have shown efficacy in delivering agents to brain tumors and injury sites.
- Spinal cord injuries (SCIs) present challenges for targeted therapeutic delivery.
Purpose of the Study:
- To investigate the affinity of tail vein-injected LCMs for an injured rat spinal cord.
- To determine the temporal and spatial accumulation patterns of LCMs at the SCI site.
Main Methods:
- Rats with compressive thoracic spinal cord lesions were injected with lipid-soluble fluorescent dye-labeled LCMs.
- LCM accumulation and glial fibrillary acidic protein (GFAP) expression were analyzed using confocal microscopy at various time points post-injury.
Main Results:
- LCMs demonstrated no significant aggregation at 1 and 6 hours post-injury.
- Clear affinity for the injured spinal cord was observed 2, 4, and 7 days after injury.
- LCM aggregation shifted from the necrotic center to white matter areas with GFAP-positive astrocytes over time.
Conclusions:
- LCMs accumulate at SCI sites, with affinity mediated by macrophages early on and astrocytes later.
- The findings support the potential of LCMs as a vehicle for concentrating lipid-soluble agents in spinal cord injury areas.
- This research opens avenues for targeted drug delivery in SCI treatment.
