PUBLICATION
Development of a Liposomal Formulation of Acetyltanshinone IIA for Breast Cancer Therapy
- Authors
- Wang, Q., Luo, M., Wei, N., Chang, A., Luo, K.Q.
- ID
- ZDB-PUB-190808-15
- Date
- 2019
- Source
- Molecular pharmaceutics 16(9): 3873-3886 (Journal)
- Registered Authors
- Chang, Alex (Kuok Weai), Luo, Kathy Qian
- Keywords
- acetyltanshinone IIA (ATA), anti-breast cancer drugs, bioavailability, mPEG-liposomes, pharmacokinetics, toxicity study
- MeSH Terms
-
- Animals
- Antineoplastic Agents/chemistry*
- Antineoplastic Agents/pharmacokinetics
- Antineoplastic Agents/therapeutic use*
- Biological Availability
- Breast Neoplasms/drug therapy*
- Cell Survival/drug effects
- Drug Compounding/methods*
- Female
- Human Umbilical Vein Endothelial Cells
- Humans
- Larva/drug effects
- Liposomes/chemistry*
- MCF-7 Cells
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Phenanthrenes/chemistry*
- Phenanthrenes/pharmacokinetics
- Phenanthrenes/therapeutic use*
- Rats
- Rats, Sprague-Dawley
- Tumor Burden/drug effects
- Xenograft Model Antitumor Assays
- Zebrafish/embryology
- PubMed
- 31389706 Full text @ Mol. Pharm.
Citation
Wang, Q., Luo, M., Wei, N., Chang, A., Luo, K.Q. (2019) Development of a Liposomal Formulation of Acetyltanshinone IIA for Breast Cancer Therapy. Molecular pharmaceutics. 16(9):3873-3886.
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.
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