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Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles
Published on: August 2, 2016
Construction of a two-in-one liposomal system (TWOLips) for tumor-targeted combination therapy
Tingting Su1, Yingying Long1, Chunyue Deng1
1College of Pharmaceutical Sciences, Key Laboratory of Luminescence and Real-time Analytical Chemistry, Ministry of Education, Southwest University, Chongqing 400715, China.
Abstract:
In oncology, there is a growing need for simpler, more selective methods to deliver drug therapies directly to the tumor site. For combination therapies, simultaneous targeted delivery of multiple drugs would represent a significant improvement. In contrast to previous work that took a de novo approach, we constructed a novel two-in-one liposomal system (TWOLips) from two single drug-loaded liposomes. Our results demonstrated that TWOLips could be prepared by a simple process, through silica coating of one liposome and incubation with the second liposome. TWOLips had a mean diameter of 100 nm, relatively high drug loading rates (96.8%±0.9% for doxorubicin and 78.4%±1.2% for combretastatin), and high storage stability. TWOLips modification by adding a targeting moiety, an all D-amino acid peptide derived from a natural vascular endothelial growth factor, resulted in strong, selective binding to vascular endothelial growth factor receptor 2, a tumorigenesis marker, in vitro and in vivo. TWOLips significantly inhibited tumor growth and angiogenesis and enhanced survival in mice with A375 melanoma xenografts. The TWOLips system had a low potential risk of toxicity. Since the stepwise assembly could be carried further (additional drug-loaded liposomes), TWOLips shows potential as a treatment for many cancers, especially those that require multiple drugs.
Insights
A novel two-in-one liposomal system (TWOLips) enables simultaneous targeted delivery of multiple cancer drugs. This innovative approach shows significant tumor inhibition and improved survival in preclinical models with low toxicity.
Area of Science:
- Nanotechnology in drug delivery
- Oncology therapeutics
- Lipid-based drug delivery systems
Background:
- Growing need for targeted drug delivery in oncology.
- Limitations of current combination therapies require improved delivery methods.
- Simultaneous delivery of multiple drugs to tumors is a significant challenge.
Purpose of the Study:
- To develop a novel two-in-one liposomal system (TWOLips) for simultaneous targeted delivery of multiple anticancer drugs.
- To evaluate the physicochemical properties, stability, and targeting efficacy of TWOLips.
- To assess the therapeutic potential of TWOLips in preclinical cancer models.
Main Methods:
- Constructed TWOLips by silica coating one liposome and incubating with a second drug-loaded liposome.
- Characterized TWOLips for size, drug loading efficiency (doxorubicin, combretastatin), and storage stability.
- Modified TWOLips with a vascular endothelial growth factor (VEGF) targeting moiety for receptor binding studies in vitro and in vivo.
- Evaluated tumor growth, angiogenesis inhibition, and survival in A375 melanoma xenograft mouse models.
Main Results:
- TWOLips were prepared via a simple process with a mean diameter of 100 nm.
- Achieved high drug loading rates (96.8%±0.9% doxorubicin, 78.4%±1.2% combretastatin) and good storage stability.
- Targeted TWOLips demonstrated selective binding to VEGF receptor 2.
- TWOLips significantly inhibited tumor growth and angiogenesis, enhancing survival in mice with low toxicity.
Conclusions:
- TWOLips represent a simple, stable, and effective platform for simultaneous delivery of multiple drugs in cancer therapy.
- Targeted TWOLips show promising efficacy in reducing tumor growth and angiogenesis, with potential for treating various cancers.
- The stepwise assembly allows for further modifications, highlighting TWOLips' versatility for combination cancer treatments.
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