Non-ionic Gd-based MRI contrast agents are optimal for encapsulation into phosphatidyldiglycerol-based thermosensitive liposomes

Thermosensitive liposomes (TSL) with encapsulated magnetic resonance imaging (MRI) longitudinal relaxation time (T1) contrast agents (CAs) have been proposed for MRI assisted interventional thermotherapy in solid tumors. Here the feasibility of 6 clinically approved CAs (Gd-DTPA, Gd-BOPTA, Gd-DOTA,...

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Bibliographic Details
Published in:Journal of controlled release 2013-02, Vol.166 (1), p.22-29
Main Authors: Hossann, Martin, Wang, Tungte, Syunyaeva, Zulfiya, Wiggenhorn, Michael, Zengerle, Anja, Issels, Rolf D., Reiser, Maximilian, Lindner, Lars H., Peller, Michael
Format: Article
Language:English
Subjects:
1,2-Dipalmitoylphosphatidylcholine - analogs & derivatives
1,2-Dipalmitoylphosphatidylcholine - chemistry
Contrast media
Contrast Media - administration & dosage
Contrast Media - chemistry
Drug Carriers - chemistry
Drug Compounding
encapsulation
Gadolinium DTPA - administration & dosage
Gadolinium DTPA - chemistry
Gd-based contrast agent
heat
hydrolysis
Hyperthermia
immunoglobulin G
Liposomes
Magnetic Resonance Imaging
neoplasms
osmolality
Particle Size
permeability
phase transition
Phosphatidylcholines - chemistry
Phosphatidylglycerols - chemistry
Phosphatidyloligoglycerol
phospholipids
Proton magnetic resonance
shelf life
Surface Properties
temperature
Thermosensitive liposomes
thermotherapy
Transition Temperature
zeta potential
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Summary:Thermosensitive liposomes (TSL) with encapsulated magnetic resonance imaging (MRI) longitudinal relaxation time (T1) contrast agents (CAs) have been proposed for MRI assisted interventional thermotherapy in solid tumors. Here the feasibility of 6 clinically approved CAs (Gd-DTPA, Gd-BOPTA, Gd-DOTA, Gd-BT-DO3A, Gd-DTPA-BMA, and Gd-HP-DO3A) for formulation into TSL was investigated. CAs were passively encapsulated with 323mOskg−1 into 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-distearoyl-sn-glycero-3-phosphocholine/1,2-dipalmitoyl-sn-glycero-3-phosphodiglycerol 50/20/30 (mol/mol) TSL (DPPG2-TSL) to obtain stable formulations. T1 relaxivity (r1) and diffusive permeability to water (Pd) across the membrane were determined. Shelf life at 4°C was investigated by determining lysolipid content up to 10weeks after preparation. All preparations were monodispersed with comparable small vesicle sizes (~135nm). Neither zeta potential nor phase transition temperature (Tm) was affected by the CA. The formulations showed an increase in r1 in the temperature range between 38 and 44°C. This correlated with the phase transition. Change in r1 (Δr1=r1(45.3°C)−r1(37.6°C)) and r1 (T
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2012.12.003