MRI evaluation of the antitumor activity of paramagnetic liposomes loaded with prednisolone phosphate

作者：Cittadino Evelina; Ferraretto Marisa; Torres Elena; Maiocchi Alessandro; Crielaard Bart J; Lammers Twan; Storm Gert; Aime Silvio; Terreno Enzo^*

来源：European Journal of Pharmaceutical Sciences, 2012, 45(4): 436-441.

DOI：10.1016/j.ejps.2011.08.022

• MRI
• Liposomes
• Glucocorticoid
• Gd-based agent
• Image-guided drug delivery
• Theranostic agents

The design of long circulating liposomes co-loaded with the glucocorticoid prednisolone phosphate (PLP) and the amphiphilic paramagnetic contrast agent Gd-DOTAMA(C-18)(2) allowed the MRI-guided in vivo visualization of the delivery and biodistribution of PLP, as well as the monitoring of drug efficacy. The performance of this theranostic probe was investigated in a mouse model bearing a melanoma B16 syngeneic tumor. %26lt;br%26gt;The release kinetics of the drug were evaluated in vitro where it displayed a peculiar behavior characterized by a fast process (completed in few hours) involving only a small portion (%26lt;5%) of the drug. Interestingly, the incorporation of the amphiphilic imaging reporter in the liposomal bilayer slightly increased the amount of the fast-release portion (%26lt;10%), thus suggesting that it could be attributed to a drug fraction embedded in the liposomal bilayer. In fact, the release of a hydrophilic imaging probe encapsulated in the inner core of the same long circulating liposomes formulated for carrying the drug, displayed different, single-step, kinetics. %26lt;br%26gt;The in vivo monitoring of the antitumor activity of the nanomedicine revealed that the incorporation of the MRI probe into the liposome bilayer did not significantly affect the drug efficacy. %26lt;br%26gt;The in vivo experiments also indicated a relevant and fast liposome uptake from macrophage-rich organs like spleen and liver, which reduced the tumor accumulation of the liposomes. The accumulation of the amphipatic MRI label caused the occurrence of a long-term residual T-1 contrast still detectable 1 week after injection.

• 出版日期2012-3-12