Development of a Liposomal Formulation of Acetyltanshinone IIA for Breast Cancer Therapy

Qi Wang, Man Luo, Na Wei, Alex Y Chang, Kathy Qian Luo

Research output: Contribution to journalArticle

Abstract

Acetyltanshinone IIA (ATA), synthesized in our group exhibiting good anti-breast cancer effects, is expected to replace the commonly used anti-ER+ breast cancer (breast cancer cells overexpressing the estrogen receptor) drug tamoxifen. To promote the clinical progress of ATA, polyethylene glycol (PEG)-modified liposomes were used to encapsulate ATA along with improving its bioavailability and in vivo anticancer efficiency. The resulting liposomal ATA exhibited a spherical shape with an average size of 188.5 nm. In vitro evaluations showed that liposomal ATA retained the anti-breast cancer efficacy of ATA while exerting much less cytotoxicity toward noncancerous cells. Significantly, pharmacokinetics analysis showed that the AUC0-24h of liposomal ATA was 59 times higher than that of free ATA, demonstrating increased bioavailability of ATA. Preclinical experiments demonstrated that liposomal ATA reduced the growth of ER-positive human breast tumor xenografts by 73% in nude mice, and the liposomal ATA exhibited a much lower level of toxicity than that of free ATA with respect to zebrafish larval mortality, body formation, and heart function during development. Moreover, 7-day and 21-day tissue toxicity levels were determined in mice by intravenous administration of a maximum dosage of liposomal ATA (120 mg/kg). The results showed no obvious tissue damage in major organs, including the heart, liver, spleen, kidney, and brain. In summary, we have developed a clinical formulation of liposomal ATA with the high bioavailability and potent efficacy for the treatment of ER-positive breast cancer.

Original languageEnglish (US)
JournalMolecular Pharmaceutics
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Breast Neoplasms
Therapeutics
Biological Availability
acetyltanshinone IIA
Zebrafish
Tamoxifen
Heterografts
Nude Mice
Liposomes
Estrogen Receptors
Intravenous Administration
Spleen
Pharmacokinetics
Kidney
Mortality
Liver
Brain
Growth

Keywords

  • acetyltanshinone IIA (ATA)
  • anti-breast cancer drugs
  • bioavailability
  • mPEG-liposomes
  • pharmacokinetics
  • toxicity study

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Development of a Liposomal Formulation of Acetyltanshinone IIA for Breast Cancer Therapy. / Wang, Qi; Luo, Man; Wei, Na; Chang, Alex Y; Luo, Kathy Qian.

In: Molecular Pharmaceutics, 01.01.2019.

Research output: Contribution to journalArticle

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