Liposomes have been widely used delivery systems, particularly relevant to the development of
cancer therapeutics. Numerous
liposome-based drugs are in the clinic or in clinical trials today against multiple
tumor types; however, systematic studies of
liposome interactions with solid or metastatic
tumor nodules are scarce. This study is describing the in vitro interaction between
liposomes and avascular human prostate (LNCaP-LN3)
tumor spheroids. The ability of fluorescently labelled liposomal delivery systems of varying physicochemical characteristics to penetrate within multicellular
tumor spheroids has been investigated by confocal
laser scanning microscopy. A variety of
liposome characteristics and experimental parameters were investigated, including
lipid bilayer composition, duration of
liposome-spheroid interaction, mean
liposome size, steric stabilization of
liposomes. Electrostatic binding between cationic
liposomes and spheroids was very efficient; however, it impeded any significant penetration of the vesicles within deeper layers of the
tumor spheroid. Small
unilamellar liposomes of neutral surface character did not bind as efficiently but exhibited enhanced penetrative transport capabilities closer to the
tumor core.
Polymer-coated (sterically stabilised)
liposomes exhibited almost no interaction with the spheroid, indicating that their limited diffusion within avascular tissues may be a limiting step for their use against
micrometastases. Multicellular
tumor spheroids were used as models of solid
tumor interstitium relevant to delivery systems able to extravasate from the microcapillaries or as models of prevascularized
micrometastases. This study illustrates that interactions between
liposomes and other drug delivery systems with multicellular
tumor spheroids can offer critically important information with respect to optimizing solid or micrometastatic
tumor delivery and targeting strategies.