PuSH - Publication Server of Helmholtz Zentrum München: Non-ionic Gd-based MRI contrast agents are optimal for encapsulation into phosphatidyldiglycerol-based thermosensitive liposomes.

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Hossann, M. ; Wang, T. ; Syunyaeva, Z.* ; Wiggenhorn, M.* ; Zengerle, A.* ; Issels, R.D. ; Reiser, M.* ; Lindner, L.H. ; Peller, M.*

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

J. Control. Release 166, 22-29 (2013)

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Thermosensitive liposomes (TSL) with encapsulated magnetic resonance imaging (MRI) longitudinal relaxation time (T-1) 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 323 mOs kg(-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 (DPPG(2)-TSL) to obtain stable formulations. T-1 relaxivity (r(1)) and diffusive permeability to water (P-d) across the membrane were determined. Shelf life at 4 degrees C was investigated by determining lysolipid content up to 10 weeks after preparation. All preparations were monodispersed with comparable small vesicle sizes (similar to 135 nm). Neither zeta potential nor phase transition temperature (T-m) was affected by the CA. The formulations showed an increase in r1 in the temperature range between 38 and 44 degrees C. This correlated with the phase transition.

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