Pharmacokinetics and antitumor effect of doxorubicin carried by stealth and remote loading proliposome.

PURPOSE

The aim of the study was to prepare stealth and remote loading proliposome (SRP-L) to carry doxorubicin (DXR) and evaluate the pharmacokinetics, acute toxicity, and anticancer effect of DXR carried with SRP-L.

METHODS

SRP-L was transparent solution. When SRP-L was injected into 0.9%, NaCl aqueous solution containing DXR. liposomes formed and automatically loaded DXR (SRP-L-DXR). The long circulation of SRP-L-DXR was evaluated using the pharmacokinetics of SRP-L-DXR. cardiolipin liposomal DXR (CL-DXR) and free DXR (F-DXR). The acute toxicity and anticancer effect of SRP-L-DXR were evaluated in C57BL/6 mice and murine hystocytoma M5076 tumor model.

RESULTS

The average diameter of SRP-L-DXR in pure water was 112.9 +/- 8.6 (nm) and the encapsulation efficiency of SRP-L-DXR was 96.5 +/- 0.2% in pure water, 95.5 +/- 0.1% in 5% glucose and 98.01 +/- 0.6% in 0.9% NaCl. The plasma concentration of SRP-L-DXR was much higher than those of F-DXR and CL-DXR. Compared with that of F-DXR, the SRP-L-DXR had lower acute toxicity and its anticancer effects depended upon the therapeutic treatment.

CONCLUSIONS

A novel proliposome (SRP-L) was developed, which could automatically load DXR and form SRP-L-DXR with excellent characteristics. SRP-L-DXR had lower acute toxicity but was not always more effective for the treatment of the ascitic M5076 than F-DXR.