Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer

• DOI: 10.3390/polym14010071
• Publication Date: 2021-12-27T06:06:54Z
• Authors: Nicole Lecot; Belén Dávila; Carina Sánchez; Marcelo Fernández; Mercedes González; Pablo Cabral; Hugo Cerecetto; Romina Glisoni
• Keywords: 0301 basic medicine; 4T1-TUMOR MODEL; Phenazine-5,10-dioxide; 4T1-tumor mode; IN VIVO ANTITUMORAL ACTIVITY; bioreductive-drug; phenazine-5,10-dioxide; amphiphilic pristine polymeric micelles; 4T1-tumor model; in vivo antitumoral activity; Article; 3. Good health; PHENAZINE-5; 03 medical and health sciences; Amphiphilic pristine polymeric micelles; In vivo antitumoral activity; 10-DIOXIDE; https://purl.org/becyt/ford/2.10; https://purl.org/becyt/ford/2; AMPHIPHILIC PRISTINE POLYMERIC MICELLES; Bioreductive-drug; BIOREDUCTIVE-DRUG

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 applications clinic. Amphiphilic pristine polymeric micelles (PMs) based triblock copolymers Pluronic® and Tetronic®, glycosylated derivatives their mixtures preformed-liposomes (LPS), were analyzed as strategies to improve the bioavailability of FNZ. FNZ encapsulations performed obtaining nanostructures characterized using UV-visible spectroscopy (UV-VIS), Transmission Electron Microscopy (TEM) Dynamic Light Scattering (DLS). The most promising nanoformulations for toxicity pharmacologically, at 20 mg/kg FNZ-doses, stage-IV murine metastatic-breast tumor model. results revealed that encapsulated-FNZ increased up 14 times analysis (UV-VIS, DLS TEM) confirmed interaction between vehicles In all cases appropriate encapsulation efficiencies (greater than 75%), monodisperse nanometric particle sizes (PDI = 0.180-0.335), adequate Z-potentials (-1.59 -26.4 mV), stabilities spherical morphologies obtained. vitro profile controlled releases corresponded mainly kinetic Higuchi vitro/in vivo biological studies non-toxicity relevant tumor-weight diminution (up 61%).