Microfluidic fabricated bisdemethoxycurcumin thermosensitive liposome with enhanced antitumor effect
Xia Cao1, Qi Liu1, Wenwan Shi1
1Department of Pharmaceutics, School of Pharmacy, Centre for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang, People's Republic of China; Medicinal Function Development of New Food Resources, Jiangsu Provincial Research Center, Jiangsu, People's Republic of China.
International Journal of Pharmaceutics
|May 24, 2023
Summary
Bisdemethoxycurcumin (BDMC) thermosensitive liposomes (TSL) were developed using microfluidics to overcome poor solubility. This formulation enhanced anti-tumor effects against liver cancer, particularly when combined with mild hyperthermia.
Area of Science:
- Pharmacology
- Biotechnology
- Materials Science
Background:
- Bisdemethoxycurcumin (BDMC), derived from Zingiberaceae plants, exhibits potent anti-tumor properties.
- The clinical utility of BDMC is significantly limited by its poor water solubility.
- Developing effective delivery systems is crucial for harnessing BDMC's therapeutic potential.
Purpose of the Study:
- To develop a novel thermosensitive liposome (TSL) formulation of BDMC using microfluidics.
- To enhance the solubility and anti-tumor efficacy of BDMC.
- To investigate the anti-cancer mechanisms of BDMC TSL, especially when combined with hyperthermia.
Main Methods:
- Fabrication of BDMC-loaded thermosensitive liposomes (BDMC TSL) utilizing a microfluidic chip device.
- Incorporation of glycyrrhizin as a surfactant to improve BDMC solubility.
- In vitro characterization of BDMC TSL particle size, distribution, and drug release kinetics.
- Assessment of anti-tumor effects on human hepatocellular carcinoma cells using MTT assay, live/dead staining, and flow cytometry.
- Evaluation of mechanistic pathways, including apoptosis induction via B-cell lymphoma protein level modulation, in conjunction with mild hyperthermia.
Main Results:
- Microfluidic fabrication yielded BDMC TSL with small, homogenous particle sizes and controlled release profiles.
- BDMC TSL demonstrated significant inhibition of hepatocellular carcinoma cell proliferation and migration in a dose-dependent manner.
- Combination therapy of BDMC TSL and mild hyperthermia synergistically induced cancer cell apoptosis by altering BCL-2 and BAX protein expression.
- The thermosensitive nature of the liposomes allowed for enhanced drug release and anti-tumor activity under mild hyperthermia.
Conclusions:
- Microfluidic-based formulation of BDMC TSL effectively overcomes the solubility limitations of BDMC.
- BDMC TSL exhibits potent anti-cancer activity against hepatocellular carcinoma, enhanced by mild hyperthermia.
- This approach holds promise for improving the clinical translation of BDMC as an anti-cancer therapeutic.
