Title:A Novel Long-circulating DOX Liposome: Formulation and Pharmacokinetics Studies
VOLUME: 8 ISSUE: 5
Author(s):Peihong Xiao, Juan Zhao, Yi Huang, Rongrong Jin, Zhonglan Tang, Ping Wang, Xu Song*, Hongfei Zhu *, Zibin Yang and Nie Yu
Affiliation:College of Pharmacy and Chemistry, Dali University, Dali 671000, Yunnan Province, Institute of Regulatory Science for Medical Devices, National Engineering Research Center for Bio-materials, Sichuan University, No. 29 Wangjiang Road, Chengdu 610064, Institute of Regulatory Science for Medical Devices, National Engineering Research Center for Bio-materials, Sichuan University, No. 29 Wangjiang Road, Chengdu 610064, Institute of Regulatory Science for Medical Devices, National Engineering Research Center for Bio-materials, Sichuan University, No. 29 Wangjiang Road, Chengdu 610064, Institute of Regulatory Science for Medical Devices, National Engineering Research Center for Bio-materials, Sichuan University, No. 29 Wangjiang Road, Chengdu 610064, Institute of Regulatory Science for Medical Devices, National Engineering Research Center for Bio-materials, Sichuan University, No. 29 Wangjiang Road, Chengdu 610064, Institute of Regulatory Science for Medical Devices, National Engineering Research Center for Bio-materials, Sichuan University, No. 29 Wangjiang Road, Chengdu 610064, Beibei Traditional Chinese Medical Hospital, No. 380 Jiangjun Road, Chongqing 400700, College of Pharmacy and Chemistry, Dali University, Dali 671000, Yunnan Province, Institute of Regulatory Science for Medical Devices, National Engineering Research Center for Bio-materials, Sichuan University, No. 29 Wangjiang Road, Chengdu 610064
Keywords:DOX liposome, drug loading, entrapment efficiency, Kolliphor HS15, particle size, pharmacokinetics.
Abstract:
Background: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment
because of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first
FDA-approved PEG-liposomes of DOX for the treatment of over 600,000 cancer patients, and
it can overcome doxorubicin-induced cardiomyopathy and other side effects and prolong life
span. The addition of MPEG2000-DSPE could elevate the total cost of cancer treatment.
Objective: We intended to prepare a novel DOX liposome that was prepared with inexpensive
materials egg yolk lecithin and Kolliphor HS15, thus allowing it to be much cheaper for clinical
application.
Methods: DOX liposomes were prepared using the combination of thin-film dispersion ultrasonic
method and ammonium sulfate gradient method and the factors that influenced formulation
quality were optimized. After formulation, particle size, entrapment efficiency, drug loading,
stability, and pharmacokinetics were determined.
Results: DOX liposomes were near-spherical morphology with the average size of 90 nm and
polydispersity index (PDI) of less than 0.30. The drug loading was up to 7.5%, and the entrapment
efficiency was over 80%. The pharmacokinetic studies showed that free DOX could be
easily removed and the blood concentration of free DOX group was significantly lower than
that of DOX liposomes, which indicated that the novel DOX liposome had a certain sustainedrelease
effect.
Conclusion: In summary, DOX liposome is economical and easy-prepared with prolonged circulation
time.
Lay Summary: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment because
of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first FDAapproved
PEG-liposomes of DOX to treat over 600.000 cancer patients, overcoming doxorubicin-
induced cardiomyopathy and other side effects and prolonging life span. The addition of
MPEG2000-DSPE could elevate the total cost of cancer treatment. We intend to prepare a novel
DOX liposome prepared with inexpensive materials egg yolk lecithin and Kolliphor HS15, thus
allowing it to be much cheaper for clinical use. The novel DOX liposome is economical and
easy-prepared with prolonged circulation time.
