Electrostatic Interaction on Loading of Therapeutic Peptide GLP‑1 into Porous Silicon Nanoparticles

Porous silicon (PSi) nanoparticles’ tunable properties are facilitating their use at highly challenging medical tasks such as peptide delivery. Because of many different mechanisms that are affecting the interaction between the peptide and the particle, the drug incorporation into the mesoporous delivery system is not straightforward. We have studied the adsorption and loading of incretin hormone glucagon like peptide 1 (GLP-1) on PSi nanoparticles. The results show that the highest loading degree can be achieved in pH values near the isoelectric point of peptide, and the phenomenon is independent of the surface’s zeta potential. In order to study the interaction between the peptide and the nanoparticle, we studied the adsorption with lower concentrations and noticed that also non-Coulombic forces have a big role in adsorption of GLP-1. Adsorption is effective and pH-independent especially on low peptide concentrations and onto more hydrophobic nanoparticles. Reversibility of adsorption was studied as a function of buffer pH. When the loading is compared to the total mass of the formulation, the loading degree is 29%, and during desorption experiments 25% is released in 4 h and can be considered as a reversible loading degree. Thus, the peptides adsorbed first seem to create irreversibly adsorbed layer that facilitates reversible adsorption of following peptides

Optimization of a Wet Flue Gas Desulfurization Scrubber through Mathematical Modeling of Limestone Dissolution Experiments

Dissolution rates of two very pure limestone samples were measured experimentally by means of the pH-stat method under conditions where mechanical stirring did not affect the rates considerably. The experimental results were modeled mathematically by considering the surface areas of the particles changing dynamically through the reaction; moreover, a surface factor was introduced in order to account for the nonsphericity of the particles. The surface areas were measured by means of gas adsorption and by particle size distribution (laser diffraction). Liquid-phase concentrations were measured by inductively coupled plasma optical emission spectrometry, and surface compositions were measured by X-ray spectroscopy. Furthermore, scanning electron microscope images of the samples are presented. Subsequently, an optimization model of a scrubber was developed by using the intrinsic parameters of the samples, which were determined experimentally. The optimization results indicate that up to 34–50% of the power required for milling can be saved by milling to a coarser particle size than the commonly used size of 44 μm, depending on the sample type. The present model of the lab-scale experimental study and the optimization model can be employed to estimate the actual impact that using different types of raw material would have in the operation of a wet flue gas desulfurization scrubber

Controlled Shape and Nucleation Switching of Interfacially Polymerizable Nanoassemblies by Methyl Substitution

Interfacial polymerization of uniform template-free nanostructures is very challenging since many factors play determinant roles in the final structure of the resulting nanoassemblies. Here, we present a single oxidative coupling method for the synthesis of different nanoshapes by addition or substitution of a methyl group on aniline monomers to freely alter the mechanism of monomer-to-polymer conversion. Well-defined nanotubes, nanohollows, and solid nanospheres are obtained from aniline, <i>N</i>-methylaniline, and 2-methylaniline polymerizations, respectively. We found that the extent of hydrophobicity and protonation under mild acidic conditions determines the monomers’ arrangement in micelle or droplet form, reactivity, and nucleation mechanism. These can subsequently affect the final morphology through a fusion process to form tubular structures, external flux of monomers to form nanohollows, and intradroplet oxidation to form solid nanospheres. Altered biological responses, such as cytocompatibility, redox response, hemocompatibility, and cell proliferation, are also found to be dependent on the position of the methyl group in the nanostructures

Cyclodextrin-Modified Porous Silicon Nanoparticles for Efficient Sustained Drug Delivery and Proliferation Inhibition of Breast Cancer Cells

Over the past decade, the potential of polymeric structures has been investigated to overcome many limitations related to nanosized drug carriers by modulating their toxicity, cellular interactions, stability, and drug-release kinetics. In this study, we have developed a successful nanocomposite consisting of undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) loaded with an anticancer drug, sorafenib, and surface-conjugated with heptakis­(6-amino-6-deoxy)-β-cyclodextrin (HABCD) to show the impact of the surface polymeric functionalization on the physical and biological properties of the drug-loaded nanoparticles. Cytocompatibility studies showed that the UnTHCPSi–HABCD NPs were not toxic to breast cancer cells. HABCD also enhanced the suspensibility and both the colloidal and plasma stabilities of the UnTHCPSi NPs. UnTHCPSi–HABCD NPs showed a significantly increased interaction with breast cancer cells compared to bare NPs and also sustained the drug release. Furthermore, the sorafenib-loaded UnTHCPSi–HABCD NPs efficiently inhibited cell proliferation of the breast cancer cells

Selective Optical Response of Hydrolytically Stable Stratified Si Rugate Mirrors to Liquid Infiltration

Stratified optical filters with distinct spectral features and layered surface chemistry were prepared on silicon substrates with stepwise anodic porosification and thermal carbonization. The use of differing parameters for successive carbonization treatments enabled the production of hydrolytically stable porous silicon-based layered optical structures where the adsorption of water to the lower layer is inhibited. This enables selective shifting of reflectance bands by means of liquid infiltration. The merit of using thermal carbonization for creating layered functionality was demonstrated by comparing the hydrolytic stability resulting from this approach to other surface chemistries available for Si. The functionality of the stratified optical structures was demonstrated under water and ethanol infiltration, and changes in the adsorption properties after 9 months of storage were evaluated. The changes observed in the structure were explained using simulations based on the transfer matrix method and the Bruggeman effective medium approximation. Scanning electron microscopy was used for imaging the morphology of the porous structure. Finally, the adaptability of the method for preparing complex structures was demonstrated by stacking superimposed rugate structures with several reflective bands

Versatile Cellulose-Based Carbon Aerogel for the Removal of Both Cationic and Anionic Metal Contaminants from Water

Hydrothermal carbonization of cellulose in the presence of the globular protein ovalbumin leads to the formation of nitrogen-doped carbon aerogel with a fibrillar continuous carbon network. The protein plays here a double role: (i) a natural source of nitrogen functionalities (2.1 wt %) and (ii) structural directing agent (<i>S</i>_BET = 38 m²/g). The applicability in wastewater treatment, namely, for heavy metal removal, was examined through adsorption of Cr­(VI) and Pb­(II) ion solely and in a mixed bicomponent aqueous solutions. This cellulose-based carbogel shows an enhanced ability to remove both Cr­(VI) (∼68 mg/g) and Pb­(II) (∼240 mg/g) from the targeted solutions in comparison to other carbon materials reported in the literature. The presence of competing ions showed little effect on the adsorption efficiency toward Cr­(VI) and Pb­(II)

Platelet Lysate-Modified Porous Silicon Microparticles for Enhanced Cell Proliferation in Wound Healing Applications

The new frontier in the treatment of chronic nonhealing wounds is the use of micro- and nanoparticles to deliver drugs or growth factors into the wound. Here, we used platelet lysate (PL), a hemoderivative of platelets, consisting of a multifactorial cocktail of growth factors, to modify porous silicon (PSi) microparticles and assessed both <i>in vitro</i> and <i>ex vivo</i> the properties of the developed microsystem. PL-modified PSi was assessed for its potential to induce proliferation of fibroblasts. The wound closure-promoting properties of the microsystem were then assessed in an <i>in vitro</i> wound healing assay. Finally, the PL-modified PSi microparticles were evaluated in an <i>ex vivo</i> experiment over human skin. It was shown that PL-modified PSi microparticles were cytocompatible and enhanced the cell proliferation in different experimental settings. In addition, this microsystem promoted the closure of the gap between the fibroblast cells in the wound healing assay, in periods of time comparable with the positive control, and induced a proliferation and regeneration process onto the human skin in an <i>ex vivo</i> experiment. Overall, our results show that PL-modified PSi microparticles are suitable microsystems for further development toward applications in the treatment of chronic nonhealing wounds

Delivery of Flightless I siRNA from Porous Silicon Nanoparticles Improves Wound Healing in Mice

Flightless I (Flii), a cytoskeletal actin remodelling protein, is elevated in wounds and is a negative regulator of wound healing. Gene silencing using small interfering RNA (siRNA) is an attractive approach to antagonize Flii, and therefore holds significant promise as a therapeutic intervention. The development of siRNA therapeutics has been limited by an inability of the siRNA to cross the cell surface plasma membrane of target cells and also by their degradation due to endogenous nuclease action. To overcome these limitations, suitable delivery vehicles are required. Porous silicon (pSi) is a biodegradable and high surface area material commonly used for drug delivery applications. Here we investigated the use of pSi nanoparticles (pSiNPs) for the controlled release of Flii siRNA to wounds. Thermally hydrocarbonized pSiNPs (THCpSiNPs) were loaded with Flii siRNA and then coated with a biocompatible chitosan layer. Loading regimens in the order of 50 μg of Flii siRNA per mg of pSi were achieved. The release rate of Flii siRNA was sustained over 35 h. With addition to keratinocytes <i>in vitro</i>, reduced Flii gene expression in conjunction with lowered Flii protein was observed, in concert with increased cell migration and proliferation. A significant improvement in the healing of acute excisional wounds compared to controls was observed from day 5 onward when Flii siRNA-THCpSiNPs were intradermally injected. THCpSiNPs therefore are an effective vehicle for delivering siRNA, and nanoparticle-based siRNA delivery represents a promising therapeutic approach to improve wound healing

Amine Modification of Thermally Carbonized Porous Silicon with Silane Coupling Chemistry

Thermally carbonized porous silicon (TCPSi) microparticles were chemically modified with organofunctional alkoxysilane molecules using a silanization process. Before the silane coupling, the TCPSi surface was activated by immersion in hydrofluoric acid (HF). Instead of regeneration of the silicon hydride species, the HF immersion of silicon carbide structure forms a silanol termination (Si–OH) on the surface required for silanization. Subsequent functionalization with 3-aminopropyltriethoxysilane provides the surface with an amine (−NH₂) termination, while the SiC-type layer significantly stabilizes the functionalized structure both mechanically and chemically. The presence of terminal amine groups was verified with FTIR, XPS, CHN analysis, and electrophoretic mobility measurements. The overall effects of the silanization to the morphological properties of the initial TCPSi were analyzed and they were found to be very limited, making the treatment effects highly predictable. The maximum obtained number of amine groups on the surface was calculated to be 1.6 groups/nm², corresponding to 79% surface coverage. The availability of the amine groups for further biofunctionalization was confirmed by successful biotinylation. The isoelectric point (IEP) of amine-terminated TCPSi was measured to be at pH 7.7, as opposed to pH 2.6 for untreated TCPSi. The effects of the surface amine termination on the cell viability of Caco-2 and HT-29 cells and on the in vitro fenofibrate release profiles were also assessed. The results indicated that the surface modification did not alter the loading of the drug inside the pores and also retained the beneficial enhanced dissolution characteristics similar to TCPSi. Cellular viability studies also showed that the surface modification had only a limited effect on the biocompatibility of the PSi