Liposomes uptake affected

Liposomal size has a pivotal role in macrophage uptake as the size of the liposome increases, there is enhancement of liposome uptake by macrophages, as also reported by others previously (66,67). However, although the trend remains the same, the clearance of liposomes is affected to differing extents depending on the composition (75). 

The influence of incubation temperature on liposome uptake by CVl cells was examined. The cells were ineubated with either the pol5mier-modified or the unmodified EYPC liposomes containing a fluorescent lipid, NBD-PE, at 37 or 42°C for 3 h. The amount of liposomal lipid associated with the cells after the incubation was evaluated from the fluorescence intensity of NBD-PE in the cells (Fig. 6). For the unmodified liposome, approximately the same amount of liposome was taken up by the cell at both temperatures, indicating that temperature does not affect the liposome uptake in this temperature region. In the case of the polymer-modified liposome, the amount of liposome taken up by the cell at 37°C was slightly lower than that of the unmodified liposome at the same temperature. However, at 42°C the amount became two times higher than that of the unmodified liposome. In... 

Not only will the charge of a lipid and the composition of lipids affect the delivery of biomacromolecules, but the size of the liposome may alter the transport. Mixtures of insulin with three different diameter (1.98 pm, 0.4 pm, and 0.1 pm) neutral liposomes (DPPC Choi) resulted in similar overall hypoglycemic effects to insulin alone. Contrary to this finding is the fact that pulmonary absorption of liposomal [3H] terbutaline, a small molecule, has been reported to be dependent on both composition and size of the liposomes used (Abra et al. 1990). Differences in the absorption mechanism may be the explanation for this contradictory evidence further studies are needed to clarify this and other uncertainties about the uptake mechanism of macromolecules (Patton 1996). 

Allen, T.M., Hansen, C., and Rutledge, J. (1989) Liposomes with prolonged circulation times factors affecting uptake by reticuloendothelial and other tissiSachim. Biophys. Acta, 981 27-35. 

The combination of AM and PEG (PEG-AM liposomes) on the liposome surface adversely affected target-to-normal ratio. This ratio is lower than that of AM-liposomes because of higher nonspecific capture of PEG-AM liposomes in normal tissue. However, absolute uptake in the infarct of this combination was excellent (0.25 0.14% injected dose/g) it was twofold higher than that of short-circulating AM liposomes. The intense PEG-AM liposome accumulation in the infarcted tissue resulted from the synergistic accumulation of both specific and nonspecific mechanisms. 

As is seen in Figure 6, the cells took up the polymer-modified liposomes and the unmodified liposomes approximately to the same extent at 37°C. Nevertheless, MTX encapsulated in the polymer-modified liposomes was much less effective than that entrapped in the unmodified liposomes. Since MTX must be taken up in cytoplasm to be active, it might be necessary for the anionic MTX to be delivered into low-pH compartments, such as lysosome, where MTX should be protonated and thus diffuse into cytoplasm. O Brien and collaborators showed that attachment of polyethylene glycol chains to liposome surface reduces uptake of the liposome in low-pH compartments of HeLa cell. Thus, even though the same amount of liposome was taken up by CV1 cells during the incubation, a smaller fraction of the liposomes might be taken in low-pH compartments for the polymer-modified liposomes than for the unmodified liposomes. At present, the reason why the activities of these MTX-loaded liposomes are different is unclear. However, it seems that location of the liposomes in the cell affects the appearance of the MTX activity. 

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