Composition of α-tocopheryl acetate with micellar nanocarriers and the possibility of its use as a biologically active additive

Abstract

Based on the asymmetric diblock copolymer (DBC) poly(ethylene oxide)/polyacrylic acid, effective, biocompatible and biodegradable micellar carriers were obtained for the delivery of vitamin E analogue, α-tocopheryl acetate (α-TOCA), in living organisms. The monitoring of the stability of micellar structures of the block copolymer and its composition with α-TOCA over time, in a saline solution and when the pH of the solution changes, was carried out. The stability of DBC micelles over time at pH = 3.5, partial disaggregation of micelles at pH = 9 and an increase in their aggregation in physiological solution were shown. The high stability of the α-TOCA/DBC composition formed in situ in time in the range of pH=3.5-9 and a significant decrease in its solutions of salting out effects in the presence of NaCl were established. The thermodynamic parameters of the process of the micelle formation of the pure α-TOCA in water/ethanol solution (95/5 v/v) as well as the size and morphology of its micellar structures were determined by light scattering and TEM methods. The initial α-TOCA micelles in water/ethanol solution were stable over a wide pH range, but their stability was much lower and the sensitivity to the presence of NaCl was much higher than that of DBC micelles. The dialysis method revealed the gradual release of the drug from the micellar carrier through a semipermeable membrane into the surrounding aqueous and aqueous-saline media. However, the rate and efficiency of α-TOCA release from the DBC micelles in an aqueous medium were significantly lower compared to a similar process of drug release from the pure α-TOCA dispersion. Thus, a possibility of providing of long-term controlled release of α-TOCA in the living organism due to the use of DBC micelles has been proven. Based on in vivo tests of the biological action of the composition on pregnant sows, its high bioavailability, rapid absorption, active participation in metabolic processes and positive effect on the reproductive qualities of sows compared to pure α-TOCA, were displayed, which improves the safety and productivity of newborn piglets. Key words: diblock copolymer, α-tocopheryl acetate, micellar carrier, encapsulation/release, biological action.