Encapsulation of Antioxidant Gallate Derivatives in Biocompatible Poly(ε-caprolactone)-b-Pluronic-b-Poly(ε-caprolactone) Micelles

Abstract

Formulation of antioxidant agents is still a challenge that limits their application in the biomedical field. Pentablock copolymers obtained through modification of two common PEO-PPO-PEO copolymers (Pluronic F127 and F68) with poly(ε-carprolactone) (PCL) were evaluated regarding their capability to form nanocarriers suitable for gallic acid, methyl gallate, and ethyl gallate. Applying a dialysis method, PCL/F127/PCL and PCL/F68/PCL self-assembled into spherical micelles in 0.9% NaCl aqueous solution but notably differed in critical micellar concentration (CMC), micelle core hydrophobicity, and micelle size, as evidenced by pyrene fluorescence, transmission electron microscopy, and dynamic light scattering. Cytotoxicity studies showed that the copolymers were safe at concentrations well above the CMC. Transfer of gallic acid and derivatives from aqueous medium to the micelle phase was characterized in terms of distribution constant and free energy of transference, which were shown to be strongly dependent on the hydrophobicity of the gallate derivatives and the length of PCL in the pentablock copolymer. Antioxidant activity of gallates was challenged against DPPH previously loaded in PCL/F127/PCL and PCL/F68/PCL micelles. The more the hydrophobicity of the gallate derivative, the greater the capability to enter in the micelle and to consume free radicals. In vitro release studies of gallic acid, methyl gallate, and ethyl gallate from the pentablock copolymer micelles also evidenced the influence of the hydrophobicity of both the gallate derivative and the micelle core on release rate, recording a variety of release patterns. Overall, PCL/F127/PCL and PCL/F68/PCL appear as suitable nanocarriers of potent antioxidant agents in a wide range of polarities, which may be useful for diverse therapeutic applications.

Process conditions for preparing well-defined nano- and microparticles as delivery systems of alkyl gallates

“…In the second part of this study, the encapsulation efficiency of alkyl esters of gallic acid (AGs) as well as their release kinetics were evaluated and compared as a function of particle size distribution. AGs have potent therapeutic properties, including antitumoral, antimicrobial, and antiviral properties, and are also potent antioxidants, acting as scavengers of reactive oxygen species (Fuentes et al, 2016;Lacatelly, Filippin-Monteiro, & Creczynski-Pasa, 2013;Maldonado et al, 2011;Rosso et al, 2006;Sergediene et al, 1999;Velasco, Holgado, Dobarganes, & Marquez-Ruiz, 2009). However, to the best of our knowledge, there have been no reports of the encapsulation and release of AGs in nano-and microparticles, with the exception of our previous work on nanoparticles (Chebil et al, 2018b).…”

Polymeric Antioxidant Materials for Treatment of Inflammatory Disorders

“…The same authors have also investigated the delivery of gallic acid and its ester derivatives, other types of phenolic acids. [ 62 ] A PCL‐modified poloxamer was used as a micellar carrier for the antioxidants, and the antioxidant micelles showed notable antioxidant efficiency and release profile based on the hydrophobicity of the gallate derivatives. Meanwhile, Wang et al.…”

PEO-PPO-PEO Tri-Block Copolymers for Gene Delivery Applications in Human Regenerative Medicine—An Overview

“…PEO-PPO-PEO-based micelles have been used as potential delivery systems of multiple drugs and biomolecules to increase their stability and solubility and afford protection against fast degradation [ 7 , 18 , 19 , 20 , 21 ].…”