Box-Behnken assisted development and validation of high-performance liquid chromatography method for the simultaneous determination of doxorubicin and vorinostat in polymeric nanoparticles

While histone deacetylase inhibitors, such as vorinostat, demonstrate a significant effect against hematological cancers, their application for solid tumor treatment is limited. However, there is strong evidence that combinatorial administration of vorinostat and genotoxic agents (e.g., doxorubicin) enhances the antitumoral action of both drugs against tumors. We developed a high-performance liquid chromatography method for the simultaneous determination of doxorubicin and vorinostat in polymeric nanoparticles designed to provide the parenteral administration of both drugs and increase their safety profile. We performed separation on Nucleodur C-18 Gravity column with a mixture of 10 mM potassium dihydrogen phosphate buffer pH 3.9:ACN (90:10 v/v) as mobile phase at 240 nm. The method was linear within the concentration range of 4.2–52.0 μg/ml for both drugs with limits of detection and quantification of 3.5 and 10.7 μg/ml for doxorubicin and 2.5 and 7.7 μg/ml for vorinostat, respectively. The method was precise and accurate over the concentration range of analysis. Drug loading was 5.4% for doxorubicin and 0.8% for vorinostat. Degradation of doxorubicin after irradiation was less than 5%, while the amount of vorinostat decreased at 88% under the same conditions. Thus, the validated method could be adopted for routine simultaneous analysis of doxorubicin and vorinostat in polymeric nanoparticles.     

Application of sensitive hydrogels in chemical and pH sensors

In the present work, pH-sensitive poly(vinyl alcohol)/poly(acrylic acid) (PVA/PAA) blends as well as hydrogels based on poly(N-isopropylacrylamide) (PNIPAAm), which are sensitive to organic solvent concentration in aqueous solutions, were used in silicon micromachined sensors. A sensitivity of approximately 15 mV/pH was obtained for a pH sensor with a 50 μm thick PVA/PAA hydrogel layer in a pH range above the acid exponent of acrylic acid (pK_a=4.7). The output voltage versus pH-value characteristics and the long-term signal stability of hydrogel-based sensors were investigated and the measurement conditions necessary for high signal reproducibility were determined. The influence of the preparation conditions of the hydrogel films on the sensitivity and response time of the chemical and pH sensors is discussed.