title: Use of PEGylated Immunoliposomes to Deliver Dopamine Across the Blood-Brain Barrier in a Rat Model of Parkinson's Disease.
abstract: To treat neurodegenerative disorders such as Parkinson's disease (PD), drugs must be able to cross the blood-brain barrier (BBB). Patients with PD are deficient in dopamine (DA), a neurotransmitter that cannot pass through the BBB. Liposomes modified by adding polyethylene glycol (PEGylated liposomes (PLs)) can be conjugated with antibody to form DA-PEGylated immunoliposomes (DA-PILs), and we tested their use as carriers of DA for treating PD.
  
  
  
  PEGylated liposomes (PLs) were prepared by evaporation method, and [(3) H]dopamine was encapsulated within the dried lipid film using a freeze/thaw cycle to form DA-PL. Thiolated OX26 MAb, an antitransferrin receptor monoclonal antibody, was then conjugated to 46-nm PEGylated liposomes. Particle size, zeta potential, and stability were assessed, and in vivo effects were determined after the intravenous injection of DA, DA-PL, and DA-PIL by examining brain tissue in normal rats and rats that underwent transection of the medial forebrain bundle to induce PD.
  
  
  
  The uptake of DA-PIL in the brains of this PD rat model increased about 8-fold compared with that of DA alone and about 3-fold compared with that of encapsulated DA-PEGylated liposomes (DA-PL). The volume of distribution of DA-PIL in the brain by the perfusion method was 4-fold higher than that of DA-PL, indicating that conjugation of OX26 MAb to the transferrin receptor of brain capillary endothelium mediated the effective delivery of DA to brain tissue.
  
  
  
  Dopamine can be effectively delivered to the brain by means of a PIL-based drug delivery system in PD rats.
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Science (RIPS) and Research Center for Cell Fate Control, Sookmyung Women's University Chungpa-dong 2-ga, Seoul, Korea. yskang@sm.ac.kr.
authors.forename: Young-Sook
authors.initials: YS
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Science (RIPS) and Research Center for Cell Fate Control, Sookmyung Women's University Chungpa-dong 2-ga, Seoul, Korea.
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Science (RIPS) and Research Center for Cell Fate Control, Sookmyung Women's University Chungpa-dong 2-ga, Seoul, Korea.
authors.forename: Ji-Suk
authors.initials: JS
authors.lastname: Oh
authors.affiliation: Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon, Korea.
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Song
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000008:administration & dosage* / Q000494:pharmacology; D015259:Dopamine Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016503:Drug Delivery Systems; D066298:In Vitro Techniques; D008081:Liposomes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008474:Medial Forebrain Bundle / Q000293:injuries; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D015259:Dopamine Agents; D008081:Liposomes; D011092:Polyethylene Glycols; D004298:Dopamine
keywords: Blood-brain barrier; Dopamine; OX26 monoclonal antibody; PEGylated immunoliposomes; Parkinson's disease