Stimuli-responsive properties of special micellar nanocarriers and their application for delivery of vitamin E and its analogues

Abstract

Stimuli-responsive micelles were formed by asymmetric diblock and triblock copolymers, which comprised chemically complementary (methoxy)poly(ethylene oxide) and poly(acrylic acid) blocks of different length. They were used as nanocarriers to encapsulate and deliver in vivo a poorly soluble homolog of α-tocopheryl acetate (α-TOCAh), commonly known as an analogue of vitamin E. Self-assembly of the copolymer macromolecules into special micellar structures in aqueous solutions depended on the solution pH. The micellar structures arising at pH < 5 due to hydrogen bonds between the blocks and the subsequent segregation of the hydrophobic bound segments in the aqueous medium were stable in the temperature range 20–60 °C and with dilution of the solution. The micelle formation/destruction in the copolymer solutions at pH alteration was shown to be an equilibrium process. Various morphological forms of micelles depending on the copolymer structure and the blocks’ asymmetry were revealed by the TEM method. All types of micelles showed high binding degrees (about 100%) of α-TOCAh, which did not depend on the encapsulation pathway (“in situ” or “ex situ”). Encapsulation of α-TOCAh resulted in hydrophobization of the micelle surface, thereby enhancing the aggregation of micelles in aqueous solution. Encapsulated α-tocopheryl acetate was in vivo fully digested by the animals (white mice) and showed increased biological activity, which allowed reducing its therapeutic dose by 25 times.