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Updated: Oct 7, 2025
Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles
Published on: August 28, 2015
Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1
Nicole Lecot1,2, Belén Dávila2, Carina Sánchez2
1Laboratorio de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, Montevideo 11400, Uruguay.
Abstract:
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® and Tetronic®, 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%).
Insights
Polymeric micelles and liposomes significantly enhanced the solubility and bioavailability of 2-Amino-7-fluorophenazine (FNZ) prodrug. These nanoformulations demonstrated non-toxicity and reduced tumor weight by up to 61% in preclinical models.
Area of Science:
- Nanomedicine
- Drug Delivery
- Cancer Therapeutics
Background:
- 2-Amino-7-fluorophenazine (FNZ) is a bioreducible prodrug with potential anticancer activity against hypoxic tumors.
- Poor aqueous solubility of FNZ limits its clinical application.
- Novel nanoformulations are needed to improve FNZ bioavailability and efficacy.
Purpose of the Study:
- To develop and characterize amphiphilic polymeric micelles (PMs) and liposomes (LPS) for enhanced FNZ delivery.
- To evaluate the physicochemical properties, in vitro release, and in vivo therapeutic efficacy of FNZ-loaded nanoformulations.
- To assess the toxicity and anti-tumor effects of the optimized nanoformulations.
Main Methods:
- FNZ encapsulation into PMs (Pluronic®, Tetronic® derivatives) and LPS.
- Characterization using UV-VIS spectroscopy, Transmission Electron Microscopy (TEM), and Dynamic Light Scattering (DLS).
- In vitro drug release studies, toxicity assays, and in vivo pharmacological evaluation in a murine metastatic breast tumor model.
Main Results:
- FNZ solubility increased up to 14-fold with nanoformulation.
- Nanoformulations exhibited high encapsulation efficiency (>75%), monodisperse particle sizes (PDI 0.180-0.335), and adequate stability.
- In vitro release followed a Higuchi kinetic model; in vivo studies showed significant tumor weight reduction (up to 61%) with no observed toxicity.
Conclusions:
- Amphiphilic polymeric micelles and liposomes are effective carriers for improving FNZ solubility and bioavailability.
- These nanoformulations offer a promising strategy for enhancing the therapeutic efficacy of FNZ against hypoxic tumors.
- The developed FNZ nanoformulations are non-toxic and demonstrate significant tumor regression in vivo.
