title: Improved paramagnetic liposomes for MRI visualization of pH triggered release.
abstract: This work aims at assessing the in vitro potential of paramagnetic pH sensitive liposomes as imaging tools for visualizing drug-delivery and release processes by Magnetic Resonance Imaging (MRI). pH sensitive liposomes (pSLs) were formulated using the fusogenic phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), the membrane stabilizer D-α-tocopherol-hemisuccinate (THS), and were loaded with several paramagnetic complexes including the clinically approved Gadoteridol (marketed as ProHance™). The proposed formulation allows the fast and full release of Gadoteridol at pH 5.5. The leakage of the imaging reporter from the vesicles was associated with a relaxivity enhancement that allowed its visualization by MRI. It was observed that the release mechanism implies the protonation of the THS basic sites that leads to vesicle aggregation, thus enabling the expression of the fusogenic property of POPE. Attempts for improving the MRI properties of pSLs were pursued through the encapsulation of imaging agents with higher relaxivity than Gadoteridol, but it was observed that the release kinetic can be significantly affected by the probe size. Aiming at preparing stealth pSLs, PEG chains were conjugated to the external surface of the vesicles via cleavable disulphide bridges. Such nanomedicines do not release their content at acidic pH as long as the coating polymer is not removed from the surface. The results obtained suggest that the liposomal formulation investigated in this work has the potential for visualizing drug-delivery and release processes by in vivo MRI preclinical studies.
authors.affiliation: Department of Chemistry IFM and Molecular & Preclinical Imaging Centers, University of Torino, Via Nizza 52, 10126, Torino, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Torres
authors.forename: Francesco
authors.initials: F
authors.lastname: Mainini
authors.forename: Roberta
authors.initials: R
authors.lastname: Napolitano
authors.forename: Franco
authors.initials: F
authors.lastname: Fedeli
authors.forename: Roberta
authors.initials: R
authors.lastname: Cavalli
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
authors.forename: Enzo
authors.initials: E
authors.lastname: Terreno
mesh_terms: D016503:Drug Delivery Systems / Q000379:methods* / Q000592:standards; D005682:Gadolinium; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000592:standards; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D006571:Heterocyclic Compounds; D008081:Liposomes; D009942:Organometallic Compounds; C062402:gadoteridol; D005682:Gadolinium