Young-Sook Kang1, Hyun-Joo Jung2, Ji-Suk Oh2, Dae-Yong Song3. 1. 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. 2. 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. 3. Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon, Korea.
Abstract
AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Dopamine can be effectively delivered to the brain by means of a PIL-based drug delivery system in PD rats.
AIM: 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. METHODS: 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. RESULTS: The uptake of DA-PIL in the brains of this PDrat 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. CONCLUSIONS:Dopamine can be effectively delivered to the brain by means of a PIL-based drug delivery system in PDrats.
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