Liposome as a carrier of
topotecan (
TPT), a promising anticancer
drug, has been reported in attempt to improve the stability and antitumor activity of
TPT. However, the biodistribution pattern of
TPT liposome in vivo and PEG-modified
liposome containing
TPT have not been studied systemically. In this paper, the in vitro stability and in vivo biodistribution behavior of several
liposomes containing
TPT with different
lipid compositions and PEG-modification were studied. Compared with the 'fluid'
liposome (S-Lip) composed of soybean
phosphatidylcholine (SPC), the 'solid'
liposome (H-Lip) composed of hydrogenated soybean
phosphatidylcholine HSPC decreased the leaking efficiency of
TPT from
liposome and enhanced the stability of
liposome in
fetal bovine serum (FBS) or human blood plasma (HBP). The results of biodistribution studies in S180
tumor-bearing mice showed that liposomal encapsulation increased the concentrations of total
TPT and the ratio of
lactone form in plasma. Compared with free
TPT, S-Lip and H-Lip resulted in 5- and 19-fold increase in the area under the curve (AUC(0-->infinity)), respectively. PEG-modified H-Lip (H-PEG) showed 3.7-fold increase in AUC(0-->infinity) compared with H-Lip, but there was no significant increase in t(1/2) and AUC(0-->infinity) for PEG-modified S-Lip (S-PEG) compared with S-Lip. Moreover, the liposomal encapsulation changed the biodistribution behavior, and H-Lip and H-PEG dramatically increased the accumulation of
TPT in
tumor, and the relative
tumor uptake ratios were 3.4 and 4.3 compared with free
drug, respectively. There was also a marked increase in the distribution of
TPT in lung when the
drug was encapsulated into H-Lip and H-PEG. Moreover, H-PEG decreased the accumulation of
TPT in bone marrow compared with unmodified H-Lip. All these results indicated that the membrane fluidity of
liposome has an important effect on in vitro stability and in vivo biodistribution pattern of
liposomes containing
TPT, and PEG-modified 'solid'
liposome may be an efficient carrier of
TPT.