New approach to treating spinal cord injury using PEG-TAT-modified, cyclosporine-A-loaded PLGA/polymeric liposomes.

Abstract

Cyclosporine-A (CsA) is an immunosuppressant agent that has shown effectiveness as a neuroprotective drug; however, it does not readily cross the blood-spinal cord barrier (BSCB), which constrains the clinical applications of CsA for the treatment of spinal cord injury (SCI). Our group recently tested the ability of novel polyethylene glycol (PEG)-transactivating-transduction protein (TAT)-modified CsA-loaded cationic multifunctional polymeric liposome-poly(lactic-co-glycolic acid) (PLGA) core/shell nanoparticles (PLGA/CsA NPs) to transport and deliver CsA across the BSCB to treat SCI. The PLGA/CsA NPs were successfully constructed. In vitro drug release studies have demonstrated that the sustained release of CsA from PLGA/CsA NPs occurs over ∼25 h. The in vivo study presented here showed that injured animals that received PLGA/CsA NPs through the tail vein, exhibited a significant up-regulation of growth-associated protein-43 (GAP-43) expression and an increased number of GAP-43-stained neurons compared with animals that received CsA or the vehicle alone. The improvement in neurological function was also evaluated by the Basso-Beattie-Bresnahan (BBB) open-field test. Moreover, fluorescein isothiocyanate (FITC)-attached PLGA/CsA NPs were successfully aggregated in the intact spinal cord 4 h after injection. Our data suggest that PLGA/CsA NPs have the potential for use as a new treatment method for SCI.

• Authors: Shi-Jie Gao, Yang Liu, Han-Jie Wang, De-Xiang Ban, Shi-Zhao Cheng, Guang-Zhi Ning, Liang-Liang Wang, Jin Chang, Shi-Qing Feng
• Journal: Journal of drug targeting (J Drug Target) Vol. 25 Issue 1 Pg. 75-82 (01 2017) ISSN: 1029-2330 [Electronic] England
• PMID: 27250819 (Publication Type: Journal Article)

Chemical References

• Drug Carriers
• GAP-43 Protein
• Gene Products, tat
• Liposomes
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Polyethylene Glycols
• Cyclosporine

Topics

• Animals
• Cyclosporine (administration & dosage, blood, therapeutic use)
• Drug Carriers (chemistry)
• Drug Liberation
• Female
• GAP-43 Protein (genetics)
• Gene Expression (drug effects)
• Gene Products, tat (chemistry)
• Lactic Acid (chemistry)
• Liposomes
• Nanoparticles (chemistry)
• Nerve Regeneration (drug effects)
• Polyethylene Glycols (chemistry)
• Polyglycolic Acid (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Rats, Wistar
• Spinal Cord (blood supply, drug effects)
• Spinal Cord Injuries (drug therapy)