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

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 [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.