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

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.

Transferrin‐bearing liposomes entrapping plumbagin for targeted cancer therapy

“…Transferrin was conjugated to the control liposomes using the thiol–maleimide “click” reaction, which is one of the most widely used thiol‐based bioconjugation techniques for grafting delivery systems with peptides, proteins, or antibodies, due to its high selectivity, rapid reaction (without heat or catalyst), and compatibility with aqueous condition (Stenzel, ; Ponte et al, ). Our results indicated high level of transferrin conjugation efficiency (50.7 ± 0.5% of the initial Tf added), which was similar to our previous conjugation rate of around 50% obtained when using dimethylsuberimidate as a crosslinking agent (Dufès et al, ) or as reported by Lopalco et al () when conjugating transferrin to dopamine‐loaded liposomes using ethyl(dimethylaminopropyl)carbodiimide coupling reagent.…”

Striking while the iron is hot: Iron metabolism and ferroptosis in neurodegeneration

“…AD and PD continue to be major health challenges with the situation set to worsen as global (Furtado et al, 2018, Lopalco et al, 2018, Bertrand et al, 2011, Huwyler et al, 1996. Iron chelators that can cross the BBB are under investigation in clinical settings now.…”

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

“…[55] The augmented retention has been confirmed by folate-, transferrin-, mannose-, and antibody-conjugated nanovehicles. [56][57][58][59] Likewise, cell-penetrating peptides (CPPs) have also been functionalized to create effective delivery nanovectors, such as TAT and iRGD. [60,61] For example, cRGD was introduced into the surface of red blood cell (RBC) membrane to achieve the targeted delivery of the anticancer drug and one photosensitizer into the tumor cells.…”

“…Although the EPR effect potentially conduces to tumor localization of nanoparticles, active cellular targeting has been developed as a complemental tactic for augmenting retention at the target sites . The augmented retention has been confirmed by folate‐, transferrin‐, mannose‐, and antibody‐conjugated nanovehicles . Likewise, cell‐penetrating peptides (CPPs) have also been functionalized to create effective delivery nanovectors, such as TAT and iRGD .…”