Influence of different doxorubicin-salt aggregates on the leakage of liposomal doxorubicin in vitro and long circulation in vivo

AimTo develop liposomes containing doxorubicin with different salts and to investigate their influence on the stability of liposomal doxorubicin in vitro and in vivo. MethodsLiposomes were prepared by the film method, treated further by extruded through nuclear membrane. The entrapment efficiency was determined by column chromatography. In vitro drug release experiments were carried out with a dialysis bag (m_w cut-off 12 000-14 000). Reverse-phase HPLC was used to study the pharmacokinetics of liposomal doxorubicin. ResultsThe particle size of liposomes with glycinate buffer, citrate buffer and ammonium sulfate as the inner water phase were (103±8), (102±12) and (97±8) nm. The ζ potential and the encapsulation ratio were (-21.3±0.5), (-21.7±0.4), (-20.9±0.7) mV and 47.8%, 96.7%, 98.6%, respectively. The leaking rate of doxorubicin from liposomes was related to the pH value of the release medium. The leaking rate increased at lowered pH. Pharmacokinetic study showed that the MRT(mean retention time)of liposomes with glycinate buffer, citrate buffer and ammonium sulfate as the inner water phase were 12.13, 23.31 and 29.79 h, respectively. Conclusion Doxorubicin showed different stability in liposomes with different inner water phases, the weaker the acid in the inner water phase, the stabler the liposome.