Hollow double-layered polymer microspheres with pH and thermo-responsive properties as nitric oxide-releasing reservoirs

Nitric oxide (NO)-releasing hollow double-layered polymer microspheres (HDPMs) with both pH- and thermo-responsive properties in aqueous media are designed and prepared by a multi-step process. Hollow double-shelled polymer microspheres with secondary amino groups are prepared by distillation precipitation copolymerization of N-isopropylacrylamide (NIPAAm) with 2-(dimethylamino)ethyl methacrylate (DMAEMA) and EGDMA in the presence of SiO2/P(2-(ethyl(boc)amino)ethyl methacrylate (bocAmEMA)-co-EGDMA) core–shell microspheres as seeds to obtain SiO2/P(bocAmEMA-co-EGDMA)/P(EGDMA-co-DMAEMA-co-NIPAAm) tri-layered microspheres with subsequent removal of the silica core by hydrogen fluoride aqueous solution and deprotection of secondary amino groups with CF3CO2H. Hollow polymer microspheres with N-diazeniumdiolated NO donors are prepared by the reaction between secondary amino groups of hollow P(AmEMA-co-EGDMA)/P(EGDMA-co-DMAEMA-co-NIPAAm) microspheres and high pressure of NO (5.0 atm) under basic conditions (CH3ONa). The resulting microspheres are systematically characterized by TEM, FT-IR, TGA, elemental analysis and dynamic laser scattering (DLS). The final N-diazeniumdiolated hollow double-shelled microspheres show a controlled NO release behavior dependent on pH and temperature in the environments.