Effective delivery of dopamine to brain using pegylated immunoliposome in Parkinson's disease animal model

Abstract

The blood-brain barrier (BBB) restricts the brain uptake of manyimportant hydrophilic drugs and limits their efficacy in the treatmentof brain disease, such as Parkinson’s disease (PD) because of thepresence of tight junctions. Dopamine that has been widely used forthe treatment of PD has limitation that is difficult to transport on thebrain. Thus we examined the effectiveness of brain transport ofdopamine through BBB, using the OX26 mAb and liposomes.Dopamine was encapsulated in PEGylated liposome (PL) using thethin-film hydration method and PEGylated immunoliposome (PIL)is PL which was conjugated with OX26 mAb. The average diameterand zeta potential of the dopamine, PLs and PILs were measured bya laser-scattering technique. Pharmacokinetics of free dopamine,PLs and PILs after i.v. injection to the normal and PD rat inducedMFB transaction and brain uptakes of free dopamine, PLs and PILsusing internal carotid artery perfusion method (ICAP) in rats weredetermined. We used about 462 nm as mean diameter of PLsthat were made using the extruder and exhibited zeta potentials(61 mV). PILs were ranging in size from 42 to 50 nm. PLs andPILs contained dopamine were cleared slowly from plasmacompartment, compared to the free dopamine. The Vdssand CL of PILs in normal and PD rat were decreased and AUC of that wasincreased compared with free dopamine. Brain uptake of PILscontained dopamine was increased 7-fold compared with PLs in PDrats using ICAP method. In this study, dopamine-loaded PILsformulation showed a significantly longer stability and maintainedgood systematic effects to treat PD symptoms by performing anin vivobrain uptake and pharmacokinetic studies in PD rat models.Additionally, to transport of dopamine to the brain, it will be expectthat PILs are effective system for relieving the PD symptoms.