Dm. Lidgate et al., CONDUCTIVITY MEASUREMENT AS A CONVENIENT TECHNIQUE FOR DETERMINATION OF LIPOSOME CAPTURE VOLUME, International journal of pharmaceutics, 96(1-3), 1993, pp. 51-58
The reduction in conductivity seen between a buffer solution and a lip
osome preparation in that buffer was evaluated as a means of measuring
liposome capture volume. Using DOPC and DOPG lipid to form negatively
charged liposomes, conductivity measurements showed that conductivity
of the liposome dispersion decreased as lipid concentrations of lipos
ome preparations increased. Independent measurement of capture volumes
by gel filtration chromatography showed that conductivity changes cor
related with a liposome concentration dependent increase in capture vo
lume. It is proposed that ions from the hydrating/suspending buffer no
rmally contributing to conductivity were trapped within liposomes upon
vesicle formation. These internalized and therefore shielded ions wer
e not able to effectively contribute to conductivity of the liposome d
ispersion. For multilamellar vesicles (MLVs), capture volume was deter
mined by reduction in conductivity over a large lipid concentration ra
nge and a broad buffer ionic strength range. Capture volume could also
be determined for small unilamellar vesicles (SUVs). However, the gre
ater number of exposed phospholipid head groups in high surface area S
UVs contributed to conductivity of the liposome dispersion thereby lim
iting range of utility. A much higher ionic strength buffer (relative
to MLVs) was required before conductivity of phospholipid no longer in
fluenced conductivity of the dispersion. To expand this study, multila
mellar vesicles having either neutral (DOPC) or positive (DOPC/stearyl
amine) charge were evaluated. Similar correlations were found between
reduction in conductivity and mannitol entrapment (capture volume). Th
ese studies have confirmed that measurement of reduction in conductivi
ty provides an easy and convenient method for determining liposome cap
ture volume.