Enhanced Bioactivity of α‐Tocopheryl Succinate Based Block Copolymer Nanoparticles by Reduced Hydrophobicity

Abstract

Well-structured amphiphilic copolymers are necessary to obtain self-assembled nanoparticles (NPs) based on synthetic polymers. Highly homogeneous and monodispersed macromolecules obtained by controlled polymerization have successfully been used for this purpose. However, disaggregation of the organized macromolecules is desired when a bioactive element, such as α-tocopheryl succinate, is introduced in self-assembled NPs and this element must be exposed or released to exert its action. The aim of this work is to demonstrate that the bioactivity of synthetic NPs based on defined reversible addition-fragmentation chain transfer polymerization copolymers can be enhanced by the introduction of hydrophilic comonomers in the hydrophobic segment. The amphiphilic terpolymers are based on poly(ethylene glycol) (PEG) as hydrophilic block, and a hydrophobic block based on a methacrylic derivative of α-tocopheryl succinate (MTOS) and small amounts of 2-hydroxyethyl methacrylate (HEMA) (PEG-b-poly(MTOS-co-HEMA)). The introduction of HEMA reduces hydrophobicity and introduces “disorder” both in the homogeneous blocks and the compact core of the corresponding NPs. These NPs are able to encapsulate additional α-tocopheryl succinate (α-TOS) with high Efficiency and their biological activity is much higher than that described for the unmodified copolymers, proposedly due to more efficient degradation and release of α-TOS, demonstrating the importance of the hydrophilic–hydrophobic balance.

How the Physicochemical Properties of Manufactured Nanomaterials Affect Their Performance in Dispersion and Their Applications in Biomedicine: A Review

“…It was observed that the more-hydrophilic SMNPs disassembled and dispersed upon cellular uptake cell, whereas the hydrophobic ones remained intact within the cells [ 158 ]. It has been shown that the bioactivity of synthetic nanoparticles can be improved with the introduction of hydrophilic co-monomers in the hydrophobic segment; the introduction of 2-hydroxyethyl methacrylate in the hydrophobic block of a poly(ethylene glycol)-block-poly(α-tocopheryl succinate) reduces the hydrophobicity of the corresponding nanoparticles and increases their bioactivity [ 159 ]. TiO 2 nanoparticles, which are used in oral applications, were tested for their wetting behavior in relation to their cell–nanoparticle interactions.…”

Role of Hydrophilic Monomers in α‐Tocopherol‐Based Copolymers in Causing Cell Death by ROS Production

“…[6] Palao-Suay et al investigated polymer assembly as an extended application of TOS. [5,7,8] A methacrylated TOS (MTOS) was synthesized and its random co-polymers were prepared by copolymerization with the hydrophilic monomer N-vinylpyrrolidone (VP) in a phosphate buffer. The amphipathic polymer formed a polymeric micelle such that the passive targeting to the tumor sites became available due to enhanced permeability and retention (EPR) effect in a directed manner.…”

α-Tocopheryl Succinate-Based Polymeric Nanoparticles for the Treatment of Head and Neck Squamous Cell Carcinoma

“…Despite all these properties, the hydrophobic nature of the drug, which significantly reduces its bioavailability and therapeutic activity, is the main obstacle for the successful application of α-TOS-based clinical treatments. Our group has incorporated this molecule into nanovehicles of appropriate hydrodynamic properties in order to improve the biological activity of α-TOS [ 14 , 15 , 16 , 17 ]. In this sense, the methacrylic derivative of α-TOS was synthesized and copolymerized forming amphiphilic macromolecules that were able to self-assemble in aqueous media forming surfactant-free nanoparticles (NPs).…”