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

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

Controlled Dissolution of Griseofulvin Solid Dispersions from Electrosprayed Enteric Polymer Micromatrix Particles: Physicochemical Characterization and <i>in Vitro</i> Evaluation

The oral bio­avail­ability of a poorly water-soluble drug is often inadequate for the desired therapeutic effect. The bio­avail­ability can be improved by enhancing the physico­chemical properties of the drug (e.g., dissolution rate, permeation across the gastro­intestinal tract). Other approach include shielding the drug from the gastric metabolism and targeted drug release to obtain optimal drug absorption. In this study, a poorly water-soluble model drug, griseo­fulvin, was encapsulated as disordered solid dispersions into Eudragit L 100-55 enteric polymer micro­matrix particles, which were produced by electro­spraying. Similar micro­matrix particles were also produced with griseo­fulvin-loaded thermally oxidized mesoporous silicon (TOPSi) nanoparticles dispersed to the polymer micro­matrices. The <i>in vitro</i> drug dissolution at pH 1.2 and 6.8, and permeation at pH 7.4 across Caco-2/HT29 cell monolayers from the micro­matrix particles, were investigated. The micro­matrix particles were found to be gastro-resistant, while at pH 6.8 the griseo­fulvin was released very rapidly in a fast-dissolving form. Compared to free griseo­fulvin, the permeability of encapsulated griseo­fulvin across the intestinal cell monolayers was greatly improved, particularly for the TOPSi-doped micro­matrix particles. The griseo­fulvin solid dispersions were stable during storage for 6 months at accelerated conditions. Overall, the method developed here could prove to be a useful oral drug delivery solution for improving the bio­avail­ability of poorly water-soluble or otherwise problematic drugs

Additional file 1: of Size, Stability, and Porosity of Mesoporous Nanoparticles Characterized with Light Scattering

Contains following supplementary materials: fabrication of porous silicon nanoparticles, fabrication of silica nanoparticles, summary of silica nanoparticles' preparation conditions, summary of log-normal fitting results, absorbance of used nanoparticles, nitrogen sorption isotherms, additional TEM graphs from silica nanoparticles, fractal dimension analysis for SLS results and Kratky plots, all the studied correlations and measured zeta potential distributions. (DOCX 11779 kb

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

Inhibition of Influenza A Virus Infection <i>in Vitro</i> by Saliphenylhalamide-Loaded Porous Silicon Nanoparticles

Influenza A viruses (IAVs) cause recurrent epidemics in humans, with serious threat of lethal worldwide pandemics. The occurrence of antiviral-resistant virus strains and the emergence of highly pathogenic influenza viruses have triggered an urgent need to develop new anti-IAV treatments. One compound found to inhibit IAV, and other virus infections, is saliphenylhalamide (SaliPhe). SaliPhe targets host vacuolar-ATPase and inhibits acidification of endosomes, a process needed for productive virus infection. The major obstacle for the further development of SaliPhe as antiviral drug has been its poor solubility. Here, we investigated the possibility to increase SaliPhe solubility by loading the compound in thermally hydrocarbonized porous silicon (THCPSi) nanoparticles. SaliPhe-loaded nanoparticles were further investigated for the ability to inhibit influenza A infection in human retinal pigment epithelium and Madin-Darby canine kidney cells, and we show that upon release from THCPSi, SaliPhe inhibited IAV infection <i>in vitro</i> and reduced the amount of progeny virus in IAV-infected cells. Overall, the PSi-based nanosystem exhibited increased dissolution of the investigated anti-IAV drug SaliPhe and displayed excellent <i>in vitro</i> stability, low cytotoxicity, and remarkable reduction of viral load in the absence of organic solvents. This proof-of-principle study indicates that PSi nanoparticles could be used for efficient delivery of antivirals to infected cells