RESUMEN
Aberrant splicing and protein interaction of Ras binding domain (RBD) are associated with melanoma drug resistance. Here, cobalt or nickel doped zinc oxide (ZnO) physiometacomposite (PMC) materials bind to RNA and peptide shown by Ninhydrin staining, UV-vis, Fourier transform infrared, and circular dichroism spectroscopy. PMCs deliver splice switching oligomer (SSO) into melanoma cells or 3-D tumor spheroids shown by flow cytometry, fluorescence microscopy, and bioluminescence. Stability in serum, liver, or tumor homogenate up to 48 h and B16F10 melanoma inhibition ≥98-99% is shown. These data suggest preclinical potential of PMC for delivery of SSO, RBD, or other nucleic acid therapeutic and anticancer peptides.
RESUMEN
Developing a facile means of controlling drug release is of utmost interest in drug delivery systems. In this study, core-shell structured nanofibers containing a water-soluble porogen were fabricated via solution blow spinning, to be used as drug-loaded bioactive tissue scaffolds. Hydrophilic polyvinylpyrrolidone (PVP) and hydrophobic poly(ε-caprolactone) (PCL) were chosen to produce the core and the shell compartments of the fiber, respectively. In the core, a hydrophilic sulforhodamine B (SRB) dye was loaded as a model drug. In the PCL shell, two kinds of PVP with different molecular weights (40 kDa and 1300 kDa) were added, and the influence of PVP leaching on the SRB release and cell growth was investigated. The monolithic PCL-shelled fibers displayed a sustained SRB release with a weak burst effect. The addition of PVP in the shell induced a phase separation, forming microscale PVP domains. The PVP domain, acting as a porogen, was leached out in the medium and, as a result, the burst release of SRB was promoted. This burst effect was more prominent with the lower molecular weight PVP. The biocompatibility of the core-shell fibers was evaluated with human epidermal keratinocytes (HEK) by a cell viability assay and microscopic observation of cell proliferation. The HEK cells on fibers with a PVP/PCL composite shell formed self-assembled spherical clusters, displaying higher cell viability and proliferation than those on the monolithic PCL-shelled fibers that induced HEK cell growth in two-dimensional monolayers. The results demonstrate that the presence of hydrophilic porogens on tissue scaffolds can accelerate drug release and enhance cell proliferation by increasing surface wettability, roughness and porosity. The findings of this study provide a basic insight into the construction of bioactive three-dimensional tissue scaffolds.
RESUMEN
A novel strategy is demonstrated to improve the accuracy for determination of polyethylene (PE) density using Raman spectroscopy by optimizing the temperature of sample measurement. Spectral features associated with the conformation change of the polymer induced by temperature may provide valuable information to quantify important polymer properties such as density. To evaluate possible existence of an optimal temperature providing improved quantitative accuracy, Raman spectra of PE pellets with different densities were collected at eight different temperatures from 30 to 100 °C at 10 °C intervals. Using the spectral datasets collected at each temperature, partial least squares (PLS) models were developed using the reference PE density values determined by a standard density gradient method at 23 °C. Interestingly, the most accurate determination of density was realized at 70 °C. Multiple perturbation two-dimensional (MP2D) correlation analysis and differential scanning calorimetry (DSC) were used to examine the origin of improved accuracy at 70 °C. From these analyses, the pre-melt behavior of the PE samples was identified below their melting temperatures. Structural variations induced at the pre-melt stages enhance Raman spectral selectivity among the samples, thereby providing more accurate determination of PE density. The MP2D correlation analysis revealed the unforeseen thermal behavior of PE samples and successfully explained the improved accuracy at 70 °C.