title: Comparative evaluation of the degree of pegylation of poly(lactic-co-glycolic acid) nanoparticles in enhancing central nervous system delivery of loperamide.
abstract: OBJECTIVE
  In this study, we examined the relative cellular uptake of nanoparticles (NPs) formulated using poly(lactic-co-glycolic acid) (PLGA) polymers with increasing degree of pegylation (PLGA-PEG) and their potential to deliver loperamide to the brain of a mouse.
  
  
  METHODS
  NPs containing coumarin-6 or loperamide HCl were formulated using PLGA and PLGA-PEG, with PEG content of 5-15%, by the solvent evaporation method. NPs were characterised for size, surface charge, morphology, encapsulation efficiency and drug release. Cellular uptake of coumarin-6 NPs was examined in Caco-2 monolayers using confocal microscopy and central nervous system (CNS) delivery of loperamide HCl from the NPs was examined following intranasal administration in a mouse model.
  
  
  RESULTS
  No difference in NP characteristics was observed, irrespective of degree of pegylation, except for the surface charge which increased with increasing PEG content. PLGA-PEG NPs were found to have increased cellular uptake in comparison to PLGA NPs. Interestingly, this pattern was reflected in the CNS delivery of loperamide HCl in the mouse model.
  
  
  CONCLUSIONS
  The results from this study show that PLGA-PEG NPs have the potential to act as carriers for the noninvasive administration of therapeutic agents to the brain and possibly across other physiological barriers.
authors.affiliation: School of Pharmacy, Royal College of Surgeons in Ireland, Dublin, Ireland; Department of Pharmacology, PU-RCSI School of Medicine, Perdana University, Selangor, Malaysia.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kirby
authors.forename: Ritesh
authors.initials: R
authors.lastname: Pabari
authors.forename: Chi-Nan
authors.initials: CN
authors.lastname: Chen
authors.forename: Marwa
authors.initials: M
authors.lastname: Al Baharna
authors.forename: Jeremy
authors.initials: J
authors.lastname: Walsh
authors.forename: Zebunnissa
authors.initials: Z
authors.lastname: Ramtoola
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000378:metabolism*; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004705:Endocytosis; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008139:Loperamide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008139:Loperamide
keywords: CNS; biodegradable polymers; blood brain barrier; nanoparticles; pegylated PLGA