Targeted Delivery of Doxorubicin Liposomes for Her-2+ Breast Cancer Treatment
| Autor: | Srikanta Dash, George Olverson, Nicholas Hall, Shanzay Chaudhry, Anup K. Kundu, Qian-Jin Zhang, Tarun K. Mandal, Nusrat Chowdhury |
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| Rok vydání: | 2020 |
| Předmět: |
Receptor
ErbB-2 Pharmaceutical Science Breast Neoplasms 02 engineering and technology Aquatic Science Pharmacology 030226 pharmacology & pharmacy Article Polyethylene Glycols 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems 0302 clinical medicine Breast cancer Cell Line Tumor Drug Discovery Zeta potential medicine Animals Humans Doxorubicin Cytotoxicity POPC Ecology Evolution Behavior and Systematics Liposome Antibiotics Antineoplastic Ecology Chemistry General Medicine 021001 nanoscience & nanotechnology medicine.disease Liposomes Cancer cell Nanoparticles Doxorubicin Hydrochloride Female 0210 nano-technology Agronomy and Crop Science medicine.drug |
| Zdroj: | AAPS PharmSciTech |
| ISSN: | 1530-9932 |
| Popis: | The adverse side effects and toxicity caused by the non-targeted delivery of doxorubicin has emphasized the demand of emerging a targeted delivery system. The goal of this study is to enhance the delivery of doxorubicin by formulating an aptamer-labeled liposomal nanoparticle delivery system that will carry and deliver doxorubicin specifically into Her-2+ breast cancer cells. Twelve liposomal batches were prepared using different saturated (HSPC and DPPC) and unsaturated (POPC and DOPC) lipids by thin film hydration. The liposomes were characterized for their particle size, zeta potential, and drug encapsulation efficiency. The particles were also assessed for in vitro toxicity and DOX delivery into the breast cancer cells. The formulations, F1 through F12, had a small particle size of less than 200 nm and a high entrapment efficiency of about 88 ± 5%. The best formulation, F5, had a particle size of 101 ± 14nm, zeta potential of + 5.63 ± 0.46 mV, and entrapment efficiency of ≈ 93%. The cytotoxicity studies show that the DOX-loaded liposomal formulations are more effective in killing cancer cells than the free DOX in both MCF-7 and SKBR-3 cells. The uptake studies show a significant increase in the uptake of the aptamer-labeled liposomes (i.e., F5) by more than 60% into Her-2+ MCF-7 and SKBR-3 breast cancer cells compare to non-aptamer-labeled nanoparticles. F5 also shows ≈ 1.79-fold increase in uptake of DOX in the Her-2+ cells compared to the Her-2- cells. This preliminary study indicates that aptamer-labeled F5 nanoparticles among several batches showed the highest uptake as well as the targeted delivery of doxorubicin into Her-2+ breast cancer cells. Thus, aptamer targeted approach results in substantial reduction in the dose of DOX and improves the therapeutic benefits by promoting the target specificity. |
| Databáze: | OpenAIRE |
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