title: Intranasal and intravenous administration of octa-arginine modified poly(lactic-co-glycolic acid) nanoparticles facilitates central nervous system delivery of loperamide.
abstract: OBJECTIVE
  The potential of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) surface modified with octa-arginine (R8) for central nervous system (CNS) delivery was investigated.
  
  
  METHODS
  PLGA NPs containing coumarin-6 or loperamide were surface modified using R8 and characterised for size, zeta potential, drug loading and release. We examined the cellular uptake of NPs in Madin-Darby Canine Kidney (MDCK) cells and CNS delivery of loperamide in a mouse model following intranasal (i.n.) and intravenous (i.v.) administration.
  
  
  RESULTS
  NPs were 300-350 nm in diameter and of negative zeta potential which neutralised on R8 conjugation. Cellular uptake of R8-PLGA NPs was rapid compared with PLGA NPs and correlated with a high antinociceptive effect in mice by both the i.n. and i.v. routes. Little antinociceptive effect for PLGA NPs was observed reflecting their slow uptake in the in-vitro cell model.
  
  
  CONCLUSIONS
  This study demonstrates the potential of R8-PLGA NPs as carriers of therapeutic agents to the CNS.
authors.affiliation: School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
authors.forename: Aisling
authors.initials: A
authors.lastname: O'Donnell
authors.forename: Azeema
authors.initials: A
authors.lastname: Moollan
authors.forename: Samantha
authors.initials: S
authors.lastname: Baneham
authors.forename: Melike
authors.initials: M
authors.lastname: Ozgul
authors.forename: Ritesh M
authors.initials: RM
authors.lastname: Pabari
authors.forename: Dermot
authors.initials: D
authors.lastname: Cox
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kirby
authors.forename: Zebunnissa
authors.initials: Z
authors.lastname: Ramtoola
mesh_terms: D000281:Administration, Intranasal; D061605:Administration, Intravenous; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000737:chemistry*; D002460:Cell Line; D002490:Central Nervous System; D003374:Coumarins / Q000008:administration & dosage; D004285:Dogs; D016503:Drug Delivery Systems; D005260:Female; D019344:Lactic Acid / Q000737:chemistry*; D008139:Loperamide / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D058726:Nanoconjugates / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D013844:Thiazoles / Q000008:administration & dosage
chemical_list: D000700:Analgesics; D003374:Coumarins; D058726:Nanoconjugates; D011091:Polyesters; D011108:Polymers; D013844:Thiazoles; C517282:coumarin 6; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D008139:Loperamide; D001120:Arginine
keywords: PLGA; central nervous system delivery; loperamide; nanoparticles; octa-arginine