Transferrin Functionalized Liposomes Loading Dopamine HCl: Development and Permeability Studies across an In Vitro Model of Human Blood-Brain Barrier.

Antonio Lopalco,Massimo Franco,Angela Lopedota,Nunzio Denora,Valentino Laquintana,Annalisa Cutrignelli

doi:10.3390/nano8030178

Abstract

The transport of dopamine across the blood brain barrier represents a challenge for the management of Parkinson’s disease. The employment of central nervous system targeted ligands functionalized nanocarriers could be a valid tactic to overcome this obstacle and avoid undesirable side effects. In this work, transferrin functionalized dopamine-loaded liposomes were made by a modified dehydration–rehydration technique from hydrogenated soy phosphatidylcoline, cholesterol and 1,2-stearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(poly(ethylene glycol)-2000)]. The physical features of the prepared liposomes were established with successive determination of their endothelial permeability across an in vitro model of the blood-brain barrier, constituted by human cerebral microvascular endothelial cells (hCMEC/D3). Functionalized dopamine-loaded liposomes with encapsulation efficiency more than 35% were made with sizes in a range around 180 nm, polydispersity indices of 0.2, and positive zeta potential values (+7.5 mV). Their stability and drug release kinetics were also evaluated. The apparent permeability (Pe) values of encapsulated dopamine in functionalized and unfunctionalized liposomes showed that transferrin functionalized nanocarriers could represent appealing non-toxic candidates for brain delivery, thus improving benefits and decreasing complications to patients subjected to L-dopa chronical treatment.

Highlights

The delivery of active pharmaceutical ingredients to the central nervous system (CNS) represents the most important challenge for the management of the symptoms of Parkinson’s disease (PD) and other neurodegenerative disorders, because of the various defensive barriers surrounding the brain [1,2]
It is well established that many CNS-active molecules, such as dopamine (DA), do not penetrate across the blood–brain barrier (BBB) to enter the CNS, because of their high polarity, ionized state at physiological pH and/or the deficiency of endogenous cellular membrane transporters located within the brain endothelium, which forms the blood vessel walls [3,4,5]
Different methodologies have been developed to raise the delivery of therapeutics for CNS diseases, including the development of CNS-targeted pro-drugs or co-drugs [6,7,8,9] and functionalized nanocarriers with uptake-facilitating ligands [10,11,12]

Summary

Introduction

The delivery of active pharmaceutical ingredients to the central nervous system (CNS) represents the most important challenge for the management of the symptoms of Parkinson’s disease (PD) and other neurodegenerative disorders, because of the various defensive barriers surrounding the brain [1,2]. It is well established that many CNS-active molecules, such as dopamine (DA), do not penetrate across the blood–brain barrier (BBB) to enter the CNS, because of their high polarity, ionized state at physiological pH and/or the deficiency of endogenous cellular membrane transporters located within the brain endothelium, which forms the blood vessel walls [3,4,5]. Different methodologies have been developed to raise the delivery of therapeutics for CNS diseases, including the development of CNS-targeted pro-drugs or co-drugs [6,7,8,9] and functionalized nanocarriers with uptake-facilitating ligands [10,11,12]. CNS diseases, including the development of CNS-targeted pro-drugs or co-drugs [6,7,8,9] and functionalized nanocarriers with uptake-facilitating ligands [10,11,12]. UUnntitliltotoddaya,yt,htehme mosot sstuscucecscsefsuslfuthl etrhaepryapfoyrftohretmheanmaagneamgeenmt eonf tPoDf iPsDrepisrerseepnrteesdenbtyedL-bdyopLa-d(LoDpa), a(bLiDop),raecbuirosporreocfuDrsAor, tohfaDt cAro, sthseast tchreosBsBeBs tthheroBuBgBh tthheroaucgtihvethtreaancstpivoerttmraencshpaonritsmmefcohraanmisimnofaocridasmainndo, oancciedsinatnhde,broanince, isinmethtaeboblrizaeind, ainsdmtreatnasbfoolrimzeedd taondDAtrbaynstfhoermenezdymtoe dDoApabdyectahreboexnyzlaysme e[13d–o1p5a]

Methods

Results

Conclusion