Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair

Theranostics, 2018 · DOI: 10.7150/thno.26717 · Published: August 7, 2018

Spinal Cord Injury Pharmacology Regenerative Medicine

Simple Explanation

This study introduces a novel approach to treat spinal cord injuries (SCI) by delivering multiple drugs directly to the injury site. The method uses liposomes, tiny vesicles that can carry drugs, modified to target scar tissue that forms after SCI. These liposomes encapsulate docetaxel (DTX), an anti-cancer drug, and brain-derived neurotrophic factor (BDNF), a protein that supports neuron survival and growth. To ensure the drugs reach the deeper injured spinal cord, the liposomes are embedded in a special hydrogel that transforms from a liquid to a gel at body temperature. This hydrogel also contains acidic fibroblast growth factor (aFGF), another protein promoting cell growth. The combined therapy aims to overcome the limitations of single-drug treatments by addressing multiple injury mechanisms. The effectiveness of this drug delivery system was tested in rats with SCI. The results showed that the drugs were successfully delivered to the injury site, promoting nerve regeneration and improving motor function. The combination therapy also reduced scar tissue formation and modulated the inflammatory response, creating a more favorable environment for recovery.

Study Duration

56 days

Participants

152 Adult female Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
The scar-homing liposomes (CAQK-LIPs) specifically bind to the lesion site after SCI, enabling targeted drug delivery.
2
The thermosensitive heparin-modified poloxamer hydrogel (HP) prolongs the retention time of CAQK-LIPs within the spinal cord, ensuring sustained drug release.
3
The combined application of growth factors (GFs) and docetaxel (DTX) in the hydrogel (CAQK-LIP-GFs/DTX@HP) significantly improves pathology and motor function after SCI in rats, promoting axonal regeneration and re-myelination.

Research Summary

This study introduces a novel multi-drug delivery system for spinal cord injury (SCI) repair, utilizing scar-homing liposomes loaded with docetaxel (DTX) and growth factors (GFs) embedded in a thermosensitive hydrogel. The system effectively delivers multiple drugs to the injured site, promoting neuro-regeneration by improving neuronal survival and plasticity, and fostering a more permissive extracellular matrix environment with improved regeneration potential. In vivo and in vitro testing demonstrated the targeting ability of the CAQK peptide to the lesion scar after SCI, and comprehensive evaluations confirmed the profound effect of the drug-loaded hydrogel in promoting functional recovery.

Practical Implications

Clinical Translation

The scar-homing delivery system offers a promising translational prospect for the clinical treatment of SCI due to its efficiency in co-loading and delivering multiple drugs with distinct physicochemical properties.

Targeted Drug Delivery

The approach provides a strategy for converting agents with unfavorable pharmacokinetic profiles into efficient drugs for SCI treatment.

Combination Therapy

The study validates the effectiveness of combining neuroprotective and neuroregenerative agents to target multiple aspects of SCI, paving the way for more comprehensive treatment strategies.

Study Limitations

1
The underlying mechanisms of DTX on promoting axon growth and the relationships between axon growth, scar reduction, and functional recovery remain to be further elucidated.
2
Additional research is needed on the interaction of multiple drugs within the hydrogel and their in vivo biodegradation.
3
Systemic administration of the scar-targeted CAQK-LIP-GFs/ DTX can be considered a potential strategy for chronic SCI intervention in the future using modified liposomes that can cross the BSCB and are not ingested by the liver.

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