Indomethacin Nanoparticles for Applications in Liquid Ocular Formulations / Наночастицы С Индометацином Для Применения В Жидких Лекарственных Формах Для Глаз

Abstract

Abstract Studies in recent years have consistently shown that polymeric drug nanocarriers can be used in drug release and drug delivery systems to treat eye disorders. To achieve effective control over drug delivery, it is of crucial importance what kind of polymer and which method for drug inclusion in the nanoscale carrier we choose and what conditions are needed for the performance of this process. OBJECTIVE: The aim of this study was to produce poly(vinyl acetate) nanoparticles with indomethacin incorporated in them, assess the effect of time for dialysis of the residual monomer and initiator on the degree of incorporation of indomethacin in the nanoparticles and on the kinetics of its release, to include them in ophtalmic formulations. MATERIALS AND METHODS: Poly(vinyl acetate) nanoparticles with indomethacin were obtained by emulsion radical polymerization of vinyl acetate in the presence of indomethacin (in situ inclusion) and the absence of emulsifier. To release the residual monomer and initiator (ammonium persulfate) the obtained latexes were dialysed for 6, 9, 18 and 23 hours and then the nanoparticles were freeze-dried. Structural analysis was performed by transmission electronic microscopy, infrared spectroscopy, differential thermal analysis and thermogravimetry. Release of indomethacin was observed using ultraviolet spectroscopy. RESULTS: We proved the delayed release of indomethacin from the poly(vinyl acetate) nanocarrier and the lack of chemical interaction between the polymer and indomethacin. After 9-hour dialysis the initiator and the residual vinyl acetate were removed from the nanoparticles, while the entrapped indomethacin kept therapeutic concentrations. CONCLUSIONS: Dialysis for more than 6 and no more than 9 hours is recommended to remove the residual monomer and initiator when preparing indomethacin nanoparticles by in situ radical emulsion polymerization of vinyl acetate, for inclusion in liquid ocular formulations.