A new method for the chemo-enzymatic Baeyer–Villiger oxidation of cyclic ketones to lactones has been developed. The influence of reaction parameters and the structure of various ionic liquids were studied. Free Candida antarctica lipase B or Novozyme-435 suspended in an ionic liquid was used as the catalytic phase. The reaction was carried out under mild conditions at room temperature using 30% aq. H2O2 as the oxidation agent. 1-Butyl-3-methyl bistriflimide was the most effective ionic liquid and increased the reaction rate compared to toluene. Lipase exhibited good stability, and the ionic liquid could be easily reused. Therefore, a general chemo-enzymatic method for the oxidation of cyclohexanones and cyclobutanones to obtain adequate lactones in high yields (79–95%) has been proposed.
New type of carriers based on grafted poly(ionic liquid)s was designed for delivery of ionically attached salicylates (Sal). Choline derived ionic liquid monomeric units were successfully introduced with various content in the side chains by the controlled radical polymerization. Properly high amounts of ionic pharmaceutics in the polymer systems were achieved by the well-fitted length and grafting degree of the side chains. In aqueous solution the graft copolymers were self-assembled into the spherical superstructures with sizes up to 73 nm. Delivery studies showed “burst” release within 4 h, after that it was slower yielding ~70% of released drug within 80 h. Proposed nanocarriers supported low toxicity against human cells (NHDF and BEAS-2B), anti-inflammation activity evaluated with the use of pro-inflammatory interleukins (IL-6 and IL-8) and antibacterial activities towards E. coli. Adjustment of ionic drug content by structural parameters of graft copolymers, including grafting degree and graft length, are advantageous to tailor nanocarriers with self-assembly properties in aqueous media. Effective release process by ionic exchange and biological activity with low toxicity are promising for further development of this type of drug delivery (DDS).
24 June 2016 in ACS Sustainable Chemistry & Engineering
Amphiphilic polymer carriers were designed for the delivery of ionically bonded drugs. The ionic liquid, trimethylammonium methacrylate monomer, containing biologically active salicylate anions was selected for the preparation of copolymers via atom transfer radical polymerization (ATRP) with methyl methacrylate (MMA) or methyl acrylate (MA). The resulting polymers varied in the content and arrangement of ionic units in the chain. The self-assembly of polymers in aqueous solution yielded particles at critical micelle concentration (CMC) values below 0.1 mg ml−1 and with hydrodynamic diameters in the range of 170–290 nm, which were also visualized by TEM. Drug release studies indicated the exchange of 42–52% of salicylate anions with phosphate anions using dialysis in PBS, which corresponded to 0.15–0.25 mg of salicylate released from 1 mg of polymeric carrier.