Synthesis of nanoparticles for biological applications: drug delivery and kinetic resolution of drug precursors

Abstract

This work aims the development new nanohybrids materials and it used for the first time to the kinetic resolution of secondary alcohols. The first nanobiocatalyst was composed by lipase from Pseudomonas fluorescens immobilized on superparamagnetic nanoparticles (SPMNPs). This system was used for the kinetic resolution of rac-indanol, rac-1-phenylethanol (rac-1), rac-1-(3-bromophenyl)-1-ethanol (rac-2), rac-1-(3-methylphenyl)-1-ethanol (rac-3) and rac- 1-methyl-2-(2,6-dimethylphenoxy)ethyl acetate. The high thermal stability is mainly related to the covalent bonding between enzymes and support. Immobilized lipase on magnetic support proved to be a robust biocatalyst in the kinetic resolution, leading to (S)-indanol with high selectivity (e.e. > 99%, E > 200) in 1.75 h at 50 ºC, being reused five times without significant loss of the activity and selectivity. The kinetic resolution of rac-1, via acetylation reaction led to (R)-acetate with enantiomeric excess > 99% and to the remaining (S)-alcohol with enantiomeric excess of 94%, conversion of 49% and E > 200, after 48 h of reaction at 40 ºC. Under the same reactions conditions, rac-2 and rac-3 were slightly less reactive, since the corresponding (R)-acetates were obtained with conversion values of 44%, but with high enantioselectivity (e.e. > 99%, E > 200). The second biocatalyst was formed by lipases from Thermomyces lanuginosus (TLL) immobilized on different support. The biocatalyst was used for the kinetic resolution of rac-1-methyl-2-(2,6-dimethylphenoxy)ethyl, obtained 50%(maximum conversion) and the e.ep. of 99%. Besides that, a second study was conducted in order to the development of styrene nanoparticles (STNPs) for the controlled drug delivery via folate receptor. Initially, studies were performed in order to synthesize STNPs via miniemulsion polymerization reaction using the polymers F127 as surfactant. The hydrophobic initiator V59 was introduced into the organic phase to prevent nucleation of hydrophilic monomers in the water phase. After that, In order to evaluate the FA influence on the uptake of STNPs in cells, folic acid (FA) was covalently linked to the F127 and the modified polymer (F127-FA) was used as surfactant during the polymerization reaction of styrene. In this case, five samples were prepared by increasing the percentage of F127-FA in the aqueous phase (ST@F127 – FA 0%, ST@F127 – FA 1 %, ST@F127 – FA 3 %, ST@F127 – FA 5 % and ST@F127 – FA)