Therapeutic Use of 3β-[N-(N0,N0-Dimethylaminoethane) Carbamoyl] Cholesterol-Modified PLGA Nanospheres as Gene Delivery Vehicles for Spinal Cord Injury

PLoS ONE, 2016 · DOI: 10.1371/journal.pone.0147389 · Published: January 29, 2016

Simple Explanation

This study explores using tiny spheres made of PLGA and a special type of cholesterol called DC-Chol to deliver genes that can help heal spinal cord injuries. These spheres are designed to be safer and more effective than other methods, like using PEI, which can be toxic to cells. The researchers found that these modified spheres can carry genes into cells in the injured spinal cord, promote the growth of new blood vessels, and improve recovery.

Study Duration

6 Weeks

Participants

Adult male Sprague-Dawley rats (250–300 g)

Evidence Level

Not specified

Key Findings

1
PLGA/DC-Chol nanospheres are less cytotoxic than PEI both in vitro and in vivo, suggesting a better safety profile.
2
DC-Chol modification enhances cellular uptake and gene expression of PLGA nanospheres in mouse neural stem cells and rat spinal cord.
3
VEGF-loaded PLGA/DC-Chol nanospheres promote angiogenesis, tissue regeneration, and improved locomotor function in a rat model of spinal cord injury.

Research Summary

The study investigates DC-Chol-modified PLGA nanospheres as gene delivery vehicles for spinal cord injury, demonstrating enhanced gene transfection efficiency and reduced cytotoxicity compared to PEI. In vitro and in vivo experiments showed that PLGA/DC-Chol nanospheres improve cellular uptake, transgene expression, and promote angiogenesis in a rat spinal cord injury model. The therapeutic efficacy of PLGA/DC-Chol nanospheres loaded with the VEGF gene was confirmed by improved tissue regeneration and locomotor function recovery in rats with spinal cord injuries.

Practical Implications

Therapeutic Gene Delivery

DC-Chol-modified PLGA nanospheres show potential as a safe and effective method for therapeutic gene delivery in treating spinal cord injuries.

Enhanced Angiogenesis

VEGF-loaded nanospheres can be used to promote angiogenesis in the injured spinal cord, leading to improved tissue regeneration.

Improved Locomotor Recovery

The use of PLGA/DC-Chol nanospheres for gene delivery can enhance the recovery of locomotor function in individuals with spinal cord injuries.

Study Limitations

1
Further studies will be necessary to assess the clinical utility of this method, particularly those that are longer (i.e., more than 2 months) in duration.
2
Additional studies should assess functional recovery using electrical measurements and VEGF effect post-injection of plasmid encapsulated PLGA/DC-Col nanospheres after spinal cord injury.
3
Future studies will extend the capabilities of PLGA/DC-Chol nanospheres using the combined plasmid therapy such as BDNF and FGF in spinal cord injury models.

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