Liposome unloaded

Ferrying of molecules into cells via entry through caveolae may represent a way to traffic specifically cytotoxic molecules to specific action sites. For example, elevating the intracellular level of the sphingolipid ceramide is known to exert antimitogenic and proapoptotic effects. While ceramide is cell-permeable and displays antiapoptotic properties in vitro, systemic in vivo use of ceramide is hampered by its hydrophobicity. Using a C6-ceramide formulation in pegylated liposomes was shown to elicit a sixfold reduction in solid phase tumors, when compared to unloaded liposomes in a mouse model of breast adenocarcinoma [68],... 

A solution of DOX (0.5-20 mM) was added to the liposome dispersion (1-120 mM phospholipids) after the creation of an AS gradient. The loading was performed above the Tm of the liposome PC (>65°C for HSPC). The percent loading was followed with incubation time at the desired temperature by mixing an aliquot of the incubation mixture with washed and cleaned Dowex (50mg/per mg total DOX) to remove the free (unloaded) DOX as described below (4). 

Figure S An electron micrograph of unloaded liposomes or liposomal topotecan stabilized in a SO4 complex following loading using MnS04 gradients in the presence of the ionophore A23187 at a ratio of topotecan-to-lipid of 0.2 (wt wt). Source From Ref. 35.

Acute hypersensitivity reactions have been reported with the first infusion of pegylated liposomal doxorubicin (14,15). The symptoms included flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest and throat, and hypotension. Similar reactions have been reported after the intravenous administration of colloid imaging agents and unloaded liposomes. 

---