title: In vitro evaluation of idebenone-loaded solid lipid nanoparticles for drug delivery to the brain.
abstract: BACKGROUND
  Solid lipid nanoparticles (SLN) are regarded as interesting drug delivery systems and their preparation techniques have gained a great deal of attention.
  
  
  OBJECTIVE
  To evaluate the feasibility of preparing idebenone (IDE) loaded SLN from O/W microemulsions by the phase-inversion temperature (PIT) method. Since SLN have been proposed to improve drug delivery to the brain, IDE was chosen as model drug due to its activity in the treatment of neurodegenerative diseases.
  
  
  METHODS
  Cetyl palmitate was used as solid lipid to prepare SLN containing two surfactant/cosurfactant mixtures, isoceteth-20/glyceryl oleate (SLN A) and ceteth-20/glyceryl oleate (SLN B) by the PIT method.
  
  
  CONCLUSIONS
  All the formulations tested showed a mean particle diameter ranging from 30 to 95 nm and a single peak in size distribution. Stability tests showed that SLN B were more stable than SLN A. IDE release was dependent both on the type of primary surfactant used and the amount of loaded drug. IDE-loaded SLN were effective in inhibiting 2,2'-azobis-(2-amidinopropane)dihydrochloride (APPH)-induced lactic dehydrogenase (LDH) release and reactive oxygen species (ROS) production in primary cultures of astrocytes obtained from rat cerebral cortex. It is noteworthy that SLN B2 (containing ceteth-20 as primary surfactant and 0.7% w/w IDE) were able to prevent entirely both the LDH release and ROS production induced by APPH.
  
  
  CONCLUSIONS
  The PIT method provided SLN with good technological properties. The tested SLN could be regarded as interesting carriers to overcome the blood brain barrier and increase the efficacy of the loaded drug.
authors.affiliation: Department of Pharmaceutical Sciences, University of Catania, Catania, Italy. lmontene@unict.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Montenegro
authors.forename: Agata
authors.initials: A
authors.lastname: Campisi
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Sarpietro
authors.forename: Claudia
authors.initials: C
authors.lastname: Carbone
authors.forename: Rosaria
authors.initials: R
authors.lastname: Acquaviva
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Raciti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Puglisi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002592:Cetomacrogol / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions; D005026:Ethylene Glycols / Q000737:chemistry; D005233:Fatty Alcohols / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry; D066298:In Vitro Techniques; D053758:Nanoparticles; D010168:Palmitates / Q000737:chemistry; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013501:Surface-Active Agents / Q000737:chemistry; D014018:Tissue Distribution; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004655:Emulsions; D005026:Ethylene Glycols; D005233:Fatty Alcohols; D005989:Glycerides; D010168:Palmitates; D017382:Reactive Oxygen Species; D013501:Surface-Active Agents; D014451:Ubiquinone; C006957:cetyl palmitate; D002592:Cetomacrogol; C005953:monoolein; C036619:idebenone; C560794:isoceteth 20