Sustained intraspinal delivery of neurotrophic factor encapsulated in biodegradable nanoparticles following contusive spinal cord injury.
Glial cell line derived neurotrophic factor (GDNF) induces neuronal survival and tissue repair after spinal cord injury (SCI). A continuous GDNF supply is believed to gain greater efficacy in the neural restoration of the injured spinal cord. Accordingly, nanovehicle formulation for their efficient delivery and sustained release in injured spinal cord was examined. We first used fluorescence-labeled bovine serum albumin (FBSA) loaded in biodegradable poly(lactic acid-co-glycolic acid) (PLGA) for intraspinal administration after SCI and for in vitro study. Our results showed that the preservation of PLGA-FBSA was observed in the injured spinal cord at 24h, and PLGA-FBSA nanoparticles were well absorbed by neurons and glia, indicating that PLGA as a considerable nanovehicle for the delivery of neuroprotective polypeptide into injured spinal cord. Furthermore, intraspinal injection of GDNF encapsulated in PLGA (PLGA-GDNF) nanoparticles into the injured spinal cord proximal to the lesion center had no effect on gliosis when compared to that observed in SCI rats receiving PLGA injection. However, local administration of PLGA-GDNF effectively preserved neuronal fibers and led to the hindlimb locomotor recovery in rats with SCI, providing a potential strategy for the use of PLGA-GDNF in the treatment of SCI.
Wang
Yu-Chao
YC
Center for Nanomedicine Research, National Health Research Institutes, 35 Keyan Road, Zhunan 350, Taiwan.
Wu
Yi-Ting
YT
Huang
Hsin-Ying
HY
Lin
Hsin-I
HI
Lo
Leu-Wei
LW
Tzeng
Shun-Fen
SF
Yang
Chung-Shi
CS
D020341:Absorbable Implants; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D002478:Cells, Cultured; D003288:Contusions / Q000188:drug therapy; D004333:Drug Administration Routes; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D006016:Glycolates / Q000008:administration & dosage / Q000737:chemistry; D019344:Lactic Acid; D008124:Locomotion / Q000187:drug effects; D053758:Nanoparticles / Q000008:administration & dosage*; D009474:Neurons / Q000187:drug effects; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy*
D051100:Glial Cell Line-Derived Neurotrophic Factor; D006016:Glycolates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid