Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer
2-Amino-7-fluorophenazine 5,10-dioxide (FNZ) is a bioreducible prodrug, poorly soluble in water, with potential anticancer activity on hypoxic-tumors. This poor solubility limits its potential applications in clinic. Amphiphilic pristine polymeric micelles (PMs) based on triblock copolymers Pluronic...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | Polymers |
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| Online Access: | https://www.mdpi.com/2073-4360/14/1/71 |
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| author | Nicole Lecot Belén Dávila Carina Sánchez Marcelo Fernández Mercedes González Pablo Cabral Hugo Cerecetto Romina Glisoni |
| author_facet | Nicole Lecot Belén Dávila Carina Sánchez Marcelo Fernández Mercedes González Pablo Cabral Hugo Cerecetto Romina Glisoni |
| author_sort | Nicole Lecot |
| collection | DOAJ |
| description | 2-Amino-7-fluorophenazine 5,10-dioxide (FNZ) is a bioreducible prodrug, poorly soluble in water, with potential anticancer activity on hypoxic-tumors. This poor solubility limits its potential applications in clinic. Amphiphilic pristine polymeric micelles (PMs) based on triblock copolymers Pluronic<sup>®</sup> and Tetronic<sup>®</sup>, glycosylated derivatives and their mixtures with preformed-liposomes (LPS), were analyzed as strategies to improve the bioavailability of FNZ. FNZ encapsulations were performed and the obtaining nanostructures were characterized using UV-visible spectroscopy (UV-VIS), Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). The most promising nanoformulations were analyzed for their potential toxicity and pharmacologically, at 20 mg/kg FNZ-doses, in a stage-IV murine metastatic-breast tumor model. The results revealed that the solubility of the encapsulated-FNZ increased up to 14 times and the analysis (UV-VIS, DLS and TEM) confirmed the interaction between vehicles and FNZ. In all the cases appropriate encapsulation efficiencies (greater than 75%), monodisperse nanometric particle sizes (PDI = 0.180–0.335), adequate Z-potentials (−1.59 to −26.4 mV), stabilities and spherical morphologies were obtained. The in vitro profile of FNZ controlled releases corresponded mainly to a kinetic Higuchi model. The in vitro/in vivo biological studies revealed non-toxicity and relevant tumor-weight diminution (up to 61%). |
| first_indexed | 2024-03-10T03:25:30Z |
| format | Article |
| id | doaj.art-e0abbebe746f49b393297a78ab5526e8 |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-10T03:25:30Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-e0abbebe746f49b393297a78ab5526e82023-11-23T12:09:23ZengMDPI AGPolymers2073-43602021-12-011417110.3390/polym14010071Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast CancerNicole Lecot0Belén Dávila1Carina Sánchez2Marcelo Fernández3Mercedes González4Pablo Cabral5Hugo Cerecetto6Romina Glisoni7Laboratorio de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, Montevideo 11400, UruguayGrupo de Química Orgánica Medicinal, Instituto de Química Biológica, Facultad de Ciencias, Universidad de la República, Mataojo 2055, Montevideo 11400, UruguayGrupo de Química Orgánica Medicinal, Instituto de Química Biológica, Facultad de Ciencias, Universidad de la República, Mataojo 2055, Montevideo 11400, UruguayLaboratorio de Experimentación Animal, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, Montevideo 11400, UruguayGrupo de Química Orgánica Medicinal, Instituto de Química Biológica, Facultad de Ciencias, Universidad de la República, Mataojo 2055, Montevideo 11400, UruguayLaboratorio de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, Montevideo 11400, UruguayLaboratorio de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, Montevideo 11400, UruguayDepartamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, Buenos Aires C1113AAD, Argentina2-Amino-7-fluorophenazine 5,10-dioxide (FNZ) is a bioreducible prodrug, poorly soluble in water, with potential anticancer activity on hypoxic-tumors. This poor solubility limits its potential applications in clinic. Amphiphilic pristine polymeric micelles (PMs) based on triblock copolymers Pluronic<sup>®</sup> and Tetronic<sup>®</sup>, glycosylated derivatives and their mixtures with preformed-liposomes (LPS), were analyzed as strategies to improve the bioavailability of FNZ. FNZ encapsulations were performed and the obtaining nanostructures were characterized using UV-visible spectroscopy (UV-VIS), Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). The most promising nanoformulations were analyzed for their potential toxicity and pharmacologically, at 20 mg/kg FNZ-doses, in a stage-IV murine metastatic-breast tumor model. The results revealed that the solubility of the encapsulated-FNZ increased up to 14 times and the analysis (UV-VIS, DLS and TEM) confirmed the interaction between vehicles and FNZ. In all the cases appropriate encapsulation efficiencies (greater than 75%), monodisperse nanometric particle sizes (PDI = 0.180–0.335), adequate Z-potentials (−1.59 to −26.4 mV), stabilities and spherical morphologies were obtained. The in vitro profile of FNZ controlled releases corresponded mainly to a kinetic Higuchi model. The in vitro/in vivo biological studies revealed non-toxicity and relevant tumor-weight diminution (up to 61%).https://www.mdpi.com/2073-4360/14/1/71bioreductive-drugphenazine-5,10-dioxideamphiphilic pristine polymeric micelles4T1-tumor modelin vivo antitumoral activity |
| spellingShingle | Nicole Lecot Belén Dávila Carina Sánchez Marcelo Fernández Mercedes González Pablo Cabral Hugo Cerecetto Romina Glisoni Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer Polymers bioreductive-drug phenazine-5,10-dioxide amphiphilic pristine polymeric micelles 4T1-tumor model in vivo antitumoral activity |
| title | Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer |
| title_full | Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer |
| title_fullStr | Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer |
| title_full_unstemmed | Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer |
| title_short | Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer |
| title_sort | development and evaluation of 2 amino 7 fluorophenazine 5 10 dioxide polymeric micelles as antitumoral agents for 4t1 breast cancer |
| topic | bioreductive-drug phenazine-5,10-dioxide amphiphilic pristine polymeric micelles 4T1-tumor model in vivo antitumoral activity |
| url | https://www.mdpi.com/2073-4360/14/1/71 |
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