Use of PEGylated Immunoliposomes to Deliver Dopamine Across the Blood–Brain Barrier in a Rat Model of Parkinson's Disease

CNS Neuroscience and Therapeutics - Tập 22 Số 10 - Trang 817-823 - 2016
Young‐Sook Kang1, Hyun‐Joo Jung1, Jung Jin Oh1, Dae‐Yong Song2
1College 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
2Department of Anatomy and Neuroscience Eulji University School of Medicine Daejeon Korea

Tóm tắt

SummaryAim

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 [3H]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.

Từ khóa


Tài liệu tham khảo

10.1177/096368979800700211

10.1172/JCI24761

10.1016/S0896-6273(03)00568-3

10.1016/j.expneurol.2008.09.025

10.2165/00003088-200241040-00003

10.1124/jpet.114.216317

10.1136/jnnp.68.6.685

10.1007/s00232-015-9778-9

10.1016/j.ijpharm.2005.03.031

10.1002/cncr.20073

10.1054/bjoc.2000.1459

10.1073/pnas.93.24.14164

10.1073/pnas.130187497

10.1023/A:1019842024814

10.1602/neurorx.2.1.129

10.1016/S0076-6879(03)73032-8

10.1002/jps.2600840808

Kang YS, 1994, Use of neutral avidin improves pharmacokinetics and brain delivery of biotin bound to an avidin‐monoclonal antibody conjugate, J Pharmacol Exp Ther, 269, 344

10.1097/00004647-199707000-00001

Yoshikawa T, 1992, Biotin delivery to brain with a covalent conjugate of avidin and a monoclonal antibody to the transferrin receptor, J Pharmacol Exp Ther, 263, 897

10.1073/pnas.86.12.4761

Marsh JW, 1988, Antibody‐mediated routing of diphtheria toxin in murine cells results in a highly efficacious immunotoxin, J Biol Chem, 263, 15993, 10.1016/S0021-9258(18)37547-1

10.1016/j.expneurol.2007.09.033

10.1186/1471-2202-14-112

10.1007/s00280-014-2439-3

10.1016/j.clinph.2013.01.021

10.1017/S146239940400746X

Kong P, 2015, Neuroprotection of MAO‐B inhibitor and dopamine agonist in Parkinson disease, Int J Clin Exp Med, 8, 431

10.3109/09687688.2014.937468

10.1002/med.21252

10.1016/j.progpolymsci.2007.05.014

10.1016/j.jconrel.2007.04.001

10.1046/j.1471-4159.2001.00222.x

10.1016/0006-8993(95)00363-U

10.1016/j.biomaterials.2007.05.014

10.1007/s00280-005-0076-6

10.1016/S0005-2736(01)00409-6

10.1080/10717540590889556

10.1602/neurorx.2.1.99

10.1073/pnas.88.24.11460

10.1126/science.7871422

Wu D, 1997, Blood‐brain barrier permeability to morphine‐6‐glucuronide is markedly reduced compared with morphine, Drug Metab Dispos, 25, 768

10.1126/science.6823561

10.1212/WNL.35.7.949

10.1111/j.1365-201X.1971.tb11001.x

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CNS Neuroscience and Therapeutics

Tập 22 Số 10

817-823

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