title: 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.affiliation: a Department of Orthopaedics , Tianjin Medical University General Hospital , Tianjin , China.
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Gao
authors.affiliation: a Department of Orthopaedics , Tianjin Medical University General Hospital , Tianjin , China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: b School of Life Science, Tianjin University , Tianjin , China.
authors.forename: Han-Jie
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: a Department of Orthopaedics , Tianjin Medical University General Hospital , Tianjin , China.
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Ban
authors.affiliation: a Department of Orthopaedics , Tianjin Medical University General Hospital , Tianjin , China.
authors.forename: Shi-Zhao
authors.initials: SZ
authors.lastname: Cheng
authors.affiliation: a Department of Orthopaedics , Tianjin Medical University General Hospital , Tianjin , China.
authors.forename: Guang-Zhi
authors.initials: GZ
authors.lastname: Ning
authors.affiliation: b School of Life Science, Tianjin University , Tianjin , China.
authors.forename: Liang-Liang
authors.initials: LL
authors.lastname: Wang
authors.affiliation: b School of Life Science, Tianjin University , Tianjin , China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chang
authors.affiliation: a Department of Orthopaedics , Tianjin Medical University General Hospital , Tianjin , China.
authors.forename: Shi-Qing
authors.initials: SQ
authors.lastname: Feng
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D015696:Gene Products, tat / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D008081:Liposomes; D053758:Nanoparticles / Q000737:chemistry*; D009416:Nerve Regeneration / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017208:Rats, Wistar; D013116:Spinal Cord / Q000098:blood supply / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy*
chemical_list: D004337:Drug Carriers; D019922:GAP-43 Protein; D015696:Gene Products, tat; D008081:Liposomes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D016572:Cyclosporine
keywords: Blood-spinal cord barrier; cyclosporine-A; poly(lactic-co-glycolic acid); spinal cord injury