Docetaxel-loaded polyglutamic acid-PEG nanocapsules for the treatment of metastatic cancer
| Autor: | Atenea Soto, Noemi Csaba, María J. Alonso, Anxo Vidal, Raquel Abellan-Pose, Marcos Garcia-Fuentes, Erea Borrajo |
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| Rok vydání: | 2016 |
| Předmět: |
Biodistribution
Doublecortin Protein Lung Neoplasms Pharmaceutical Science Antineoplastic Agents 02 engineering and technology Docetaxel Mice SCID Pharmacology Nanocapsules 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Animals Humans Lung Chemistry Cancer 021001 nanoscience & nanotechnology medicine.disease Lymphatic system Polyglutamic Acid 030220 oncology & carcinogenesis Lymphatic Metastasis Drug delivery Female Taxoids Lymph Lymph Nodes Nanocarriers 0210 nano-technology medicine.drug |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 238 |
| ISSN: | 1873-4995 |
| Popis: | The design of nanomedicines with suitable physicochemical characteristics for the lymphatic targeting of drugs is critical in order to reach the lymph nodes, where metastatic cells often accumulate. Based on the known effect of particle size and surface hydrophilicity on the capacity of nanocarriers to reach the lymph nodes, here we report the formation and characterization of 100 nm polyglutamic acid-polyethylene glycol (PGA-PEG) nanocapsules together with the assessment of their potential for the treatment of cancer with lymphatic metastatic spread. To this purpose, we first studied the biodistribution of fluorescently labeled PGA-PEG nanocapsules (100 nm), following, either intravenous or subcutaneous administration. The results confirmed the accumulation of nanocapsules in the lymphatic system, especially upon subcutaneous administration. Next, we evaluated the efficacy and toxicity of the docetaxel-loaded nanocapsules in an orthotopic lung cancer model that metastasizes to the lymph nodes. As expected from the rational design, DCX-loaded PGA-PEG nanocapsules exhibited a greatly enhanced antitumoral efficacy and a reduced toxicity when compared with the commercial formulation Taxotere®. Furthermore, the administration of DCX-loaded PGA-PEG nanocapsules resulted in the practical elimination of the metastatic load in the mediastinal lymph nodes, whereas the treatment with the commercial formulation had a minor effect. Overall, these findings underscore the potential of PGA-PEG nanocapsules for the delivery of anticancer drugs to both, the tumor tissue and the metastatic lymph nodes. Therefore, they represent a promising therapy for the treatment of lung metastatic cancer. |
| Databáze: | OpenAIRE |
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