title: Ex vivo and In vivo Evaluation of Chitosan Coated Nanostructured Lipid Carriers for Ocular Delivery of Acyclovir.
abstract: BACKGROUND
  Herpes keratitis is the most common infectious cause of blindness in the developed world. It may be treated by acyclovir (ACV), however this antiviral drug is poorly soluble with low ocular bioavailability requiring high and frequent dosing. Nanostructured lipid carriers (NLCs) were investigated to improve the ocular bioavailability of ACV by enhancing corneal penetration as well as prolonging the exposure of infected cells to the antiviral agent.
  
  
  METHODS
  Cell uptake studies, ex vivo tolerance and cell uptake efficacy as well as in vivo corneal permeation of the developed lipid based formulations were investigated. NLCs were fabricated by the hot microemulsion technique and coated with 0.5% w/v chitosan. NLCs were capable of increasing the cell uptake of encapsulated fluorescein and ACV as examined by fluorescence microscopy and high performance liquid chromatography (HPLC) respectively.
  
  
  RESULTS
  When entrapped in NLCs, the antiviral efficacy of ACV was increased by 3.5 fold after 24 hrs of exposure. The in vivo corneal permeation of the formulation was studied on Albino rabbits with NLCs capable of increasing the corneal bioavailability by 4.5 fold when compared to a commercially available ACV ophthalmic ointment.
  
  
  CONCLUSIONS
  NLCs enhanced the ocular bioavailability and antiviral properties of ACV through cell internalisation, sustained release, and increased corneal permeation.
authors.affiliation: School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, P.O. Box: 92019, Auckland, New Zealand. ali.seyfoddin@aut.ac.nz.
authors.forename: Ali
authors.initials: A
authors.lastname: Seyfoddin
authors.forename: Trevor
authors.initials: T
authors.lastname: Sherwin
authors.forename: Dipika V
authors.initials: DV
authors.lastname: Patel
authors.forename: Charles N
authors.initials: CN
authors.lastname: McGhee
authors.forename: Ilva D
authors.initials: ID
authors.lastname: Rupenthal
authors.forename: John A
authors.initials: JA
authors.lastname: Taylor
authors.forename: Raida
authors.initials: R
authors.lastname: Al-Kassas
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D060433:Administration, Ophthalmic; D001682:Biological Availability; D048271:Chitosan / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003315:Cornea / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D048271:Chitosan; D000212:Acyclovir