1. Enhanced antitumor activity of doxorubicin in breast cancer through the use of poly(butylcyanoacrylate) nanoparticles
- Author
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Consolación Melguizo, José Manuel Entrena, Jose Prados, Laura Cabeza, Raquel Luque, Raúl Ortiz, María Adolfina Ruiz Martínez, José L. Arias, [Cabeza,L, Ortiz,R, Prados,J, Melguizo,C] Institute of Biopathology and Regenerative Medicine (IBIMER), Granada, Spain. [Ortiz,R] Department of Health Science, University of Jaén, Jaén, Spain. [Arias,JL, Ruiz Martínez,MA] Department of Pharmacy and Pharmaceutical Technology, University of Granada, Granada, Spain. [Prados,J, Melguizo,C] Biosanitary Institute of Granada (ibs GRANADA), SAS-Universidad de Granada, Granada, Spain. [Entrena,JM] Institute of Neuroscience, Biomedical Research Center. Animal Behavior Research Unit, Scientific Instrumentation Center, University of Granada, Armilla, Granada, Spain. [Luque,R] Service of Medical Oncology, Virgen de las Nieves Hospital, Granada, Spain., and This investigation was funded by FEDER, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III (FIS) through projects Nos PI11/01862 and PI11/02571, and by the Consejería de Salud de la Junta de Andalucía through project No PI-0338.
- Subjects
Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor [Medical Subject Headings] ,Nanopolymer ,Chemicals and Drugs::Pharmaceutical Preparations::Dosage Forms::Delayed-Action Preparations [Medical Subject Headings] ,Doxorrubicina ,Cytotoxicity ,Pharmaceutical Science ,Pharmacology ,carcinoma ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Mice ,International Journal of Nanomedicine ,Enbucrilato ,Drug Discovery ,Biodegradable polymer ,nanopolymer ,Organisms::Eukaryota::Animals [Medical Subject Headings] ,polycyclic compounds ,Medicine ,Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Acrylates::Cyanoacrylates [Medical Subject Headings] ,Adsorción ,Original Research ,Drug Carriers ,Preparaciones de acción retardada ,Nanopartículas ,General Medicine ,Enbucrilate ,Metastatic breast cancer ,Humanos ,Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Acrylates::Cyanoacrylates::Enbucrilate [Medical Subject Headings] ,Phenomena and Processes::Chemical Phenomena::Physicochemical Phenomena::Physicochemical Processes::Adsorption [Medical Subject Headings] ,Drug delivery ,Neoplasias de la mama ,cytotoxicity ,Female ,medicine.drug ,Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Polycyclic Hydrocarbons, Aromatic::Naphthacenes::Anthracyclines::Daunorubicin::Doxorubicin [Medical Subject Headings] ,Technology, Industry, Agriculture::Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanoparticles [Medical Subject Headings] ,Cell Survival ,Biophysics ,Bioengineering ,Antineoplastic Agents ,Breast Neoplasms ,macromolecular substances ,Biomaterials ,In vivo ,Cell Line, Tumor ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Toxicity Tests::Inhibitory Concentration 50 [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BL [Medical Subject Headings] ,Animals ,Humans ,Doxorubicin ,IC50 ,Chemotherapeutic drug ,Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings] ,chemotherapeutic drug ,Línea celular tumoral ,business.industry ,Concentración 50 inhibidora ,Organic Chemistry ,Carcinoma ,technology, industry, and agriculture ,biodegradable polymer ,Cianoacrilatos ,Ratones consanguíneos C57BL ,medicine.disease ,In vitro ,carbohydrates (lipids) ,Cancer cell ,Animales ,drug delivery ,Nanoparticles ,business - Abstract
The use of doxorubicin (DOX), one of the most effective antitumor molecules in the treatment of metastatic breast cancer, is limited by its low tumor selectivity and its severe side effects. Colloidal carriers based on biodegradable poly(butylcyanoacrylate) nanoparticles (PBCA NPs) may enhance DOX antitumor activity against breast cancer cells, thus allowing a reduction of the effective dose required for antitumor activity and consequently the level of associated toxicity. DOX loading onto PBCA NPs was investigated in this work via both drug entrapment and surface adsorption. Cytotoxicity assays with DOX-loaded NPs were performed in vitro using breast tumor cell lines (MCF-7 human and E0771 mouse cancer cells), and in vivo evaluating antitumor activity in immunocompetent C57BL/6 mice. The entrapment method yielded greater drug loading values and a controlled drug release profile. Neither in vitro nor in vivo cytotoxicity was observed for blank NPs. The 50% inhibitory concentration (IC50) of DOX-loaded PBCA NPs was significantly lower for MCF-7 and E0771 cancer cells (4 and 15 times, respectively) compared with free DOX. Furthermore, DOX-loaded PBCA NPs produced a tumor growth inhibition that was 40% greater than that observed with free DOX, thus reducing DOX toxicity during treatment. These results suggest that DOX-loaded PBCA NPs have great potential for improving the efficacy of DOX therapy against advanced breast cancers., This investigation was funded by FEDER, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III (FIS) through projects Nos PI11/01862 and PI11/02571, and by the Consejería de Salud de la Junta de Andalucía through project No PI-0338. The authors wish to express their gratitude to G Ortiz Ferron (CIC, University of Granada, Spain) for his skillful assistance with cytometry experiments.
- Published
- 2015