Biocompatibility of Thermally Hydrocarbonized Porous Silicon Nanoparticles and their Biodistribution in Rats

Peer reviewe

Stencil Printing-A Novel Manufacturing Platform for Orodispersible Discs

Stencil printing is a commonly used printing method, but it has not previously been used for production of pharmaceuticals. The aim of this study was to explore whether stencil printing of drug containing polymer inks could be used to manufacture flexible dosage forms with acceptable mass and content uniformity. Formulation development was supported by physicochemical characterization of the inks and final dosage forms. The printing of haloperidol (HAL) discs was performed using a prototype stencil printer. Ink development comprised of investigations of ink rheology in combination with printability assessment. The results show that stencil printing can be used to manufacture HAL doses in the therapeutic treatment range for 6-17 year-old children. The therapeutic HAL dose was achieved for the discs consisting of 16% of hydroxypropyl methylcellulose (HPMC) and 1% of lactic acid (LA). The formulation pH remained above pH 4 and the results imply that the drug was amorphous. Linear dose escalation was achieved by an increase in aperture area of the print pattern, while keeping the stencil thickness fixed. Disintegration times of the orodispersible discs printed with 250 and 500 mu m thick stencils were below 30 s. In conclusion, stencil printing shows potential as a manufacturing method of pharmaceuticals

Synthesis and Features of Luminescent Bromo- and Iodohectorite Nanoclay Materials

The smectites represent a versatile class of clay minerals with broad usage in industrial applications, e.g., cosmetics, drug delivery, bioimaging, etc. Synthetic hectorite Na-0.7(Mg5.5Li0.3)[Si8O20](OH)(4) is a distinct material from this class due to its low-cost production method that allows to design its structure to match better the applications. In the current work, we have synthesized for the first time ever nanoclay materials based on the hectorite structure but with the hydroxyl groups (OH-) replaced by Br- or I-, yielding bromohectorite (Br-Hec) and iodohectorite (I-Hec). It was aimed that these materials would be used as phosphors. Thus, OH- replacement was done to avoid luminescence quenching by multiphonon de-excitation. The crystal structure is similar to nanocrystalline fluorohectorite, having the d(001) spacing of 14.30 angstrom and 3 nm crystallite size along the 00l direction. The synthetic materials studied here show strong potential to act as host lattices for optically active species, possessing mesoporous structure with high specific surface area (385 and 363 m(2) g(-1) for Br-Hec and I-Hec, respectively) and good thermal stability up to 800 degrees C. Both materials also present strong blue-green emission under UV radiation and short persistent luminescence (ca. 5 s). The luminescence features are attributed to Ti3+/Ti-IV impurities acting as the emitting center in these materials

Influence of Surface Chemistry on Ibuprofen Adsorption and Confinement in Mesoporous Silicon Microparticles

The effect of adsorption and confinement on ibuprofen was studied by immersion loading the molecules into porous silicon (PSi) microparticles. The PSi micro particles were modified into thermally oxidized PSi (TOPSi) and thermally hydrocarbonized PSi (THCPSi) to evaluate the effects of the loading solvent and the surface chemistry on the obtainable drug payloads. The payloads, location, and the molecular state of the adsorbed drug were evaluated using thermal analysis. The results showed that after the adsorption of similar to 800 mg/cm(3) (w(drug)/v(pores)) of drug into the mesopores, depending on the solvent used in the immersion, the drug began to rapidly recrystallize on the external surface of the particles. Moderate concentrations, however, enabled payloads of 800-850 mg/cm(3) without excessive surface crystallization, and thus, there was no need for rinsing the samples to remove the externally crystallized portion. The results showed that the confined ibuprofen forms nanocrystals inside of the mesopores after approximately 200 mg/cm(3) payloads were obtained, accounting for half of the adsorbed drug amount. The presence of both crystalline and noncrystalline phases was further characterized using variable temperature solid-state nuclear magnetic resonance (NMR) measurements. The interactions between the drug molecules and the pore walls of TOPSi and THCPSi were observed using Fourier transform infrared and H-1 NMR spectroscopies, and the hydrogen bonding between the silanol groups of TOPSi and the adsorbed ibuprofen was confirmed, but having only limited effect on the overall state of the confined drug. In vitro drug permeation studies in Caco-2 and Caco-2/HT29 cocultures showed that the adsorption onto hydrophilic or hydrophobic PSi microparticles had no significant effects on the ibuprofen permeation, whether the drug was partially nanocrystalline or completely in a liquidlike state

Pretargeted PET Imaging of trans-Cyclooctene-Modified Porous Silicon Nanoparticles

Pretargeted positron emission tomography (PET) imaging based on bioorthogonal chemical reactions has proven its potential in immunoimaging. It may also have great potential in nanotheranostic applications. Here, we report the first successful pretargeted PET imaging of trans-cyclooctene-modified mesoporous silicon nanoparticles, using F-18-labeled tetrazine as a tracer. The inverse electron-demand Diels-Alder cycloaddition (IEDDA) reaction was fast, resulting in high radioactivity accumulation in the expected organs within 10 min after the administration of the tracer. The highest target-to-background ratio was achieved 120 min after the tracer injection. A clear correlation between the efficiency of the in vivo IEDDA labeling reaction and the injected amount of the tracer was observed. The radioactivity accumulation decreased with the increased amount of the co-injected carrier, indicating saturation in the reaction sites. This finding was supported by the in vitro results. Our study suggests that pretargeted imaging has excellent potential in nanotheranostic PET imaging when using high-specific-activity tracers

Multifunctional Biomimetic Nanovaccines Based on Photothermal and Weak-Immunostimulatory Nanoparticulate Cores for the Immunotherapy of Solid Tumors

An alternative strategy of choosing photothermal and weak-immunostimulatory porous silicon@Au nanocomposites as particulate cores to prepare a biomimetic nanovaccine is reported to improve its biosafety and immunotherapeutic efficacy for solid tumors. A quantitative analysis method is used to calculate the loading amount of cancer cell membranes onto porous silicon@Au nanocomposites. Assisted with foreign-body responses, these exogenous nanoparticulate cores with weak immunostimulatory effect can still efficiently deliver cancer cell membranes into dendritic cells to activate them and the downstream antitumor immunity, resulting in no occurrence of solid tumors and the survival of all immunized mice during 55 day observation. In addition, this nanovaccine, as a photothermal therapeutic agent, synergized with additional immunotherapies can significantly inhibit the growth and metastasis of established solid tumors, via the initiation of the antitumor immune responses in the body and the reversion of their immunosuppressive microenvironments. Considering the versatile surface engineering of porous silicon nanoparticles, the strategy developed here is beneficial to construct multifunctional nanovaccines with better biosafety and more diagnosis or therapeutic modalities against the occurrence, recurrence, or metastasis of solid tumors in future clinical practice.Peer reviewe

68Ga-DOTA-Siglec-9 – a new imaging tool to detect synovitistis

Conclusion: Ga-DOTA-Siglec-9 PET tracer detected VAP-1 positive vasculature in the mild synovitis of rabbits comparable with F-18-FDG, suggesting its potential for in vivo imaging of synovial inflammation in patients with rheumatic diseases.</p

Peatland Initiation, Carbon Accumulation, and 2 ka Depth in the James Bay Lowland and Adjacent Regions

Copyright © 2014 University of Colorado at Boulder, Institute of Arctic and Alpine ResearchPeatlands surrounding Hudson and James Bays form the second largest peatland complex in the world and contain major stores of soil carbon (C). This study utilized a transect of eight ombrotrophic peat cores from remote regions of central and northern Ontario to quantify the magnitude and rate of C accumulation since peatland initiation and for the past 2000 calendar years before present (2 ka). These new data were supplemented by 17 millennially resolved chronologies from a literature review covering the Boreal Shield, Hudson Plains, and Taiga Shield bordering Hudson and James Bays. Peatlands initiated in central and northern Ontario by 7.8 ka following deglaciation and isostatic emergence of northern areas to above sea level. Total C accumulated since inception averaged 109.7 ± (std. dev.) 36.2 kg C m–2. Approximately 40% of total soil C has accumulated since 2 ka at an average apparent rate of 20.2 ± 6.9 g C m–2 yr–1. The 2 ka depths correlate significantly and positively with modern gridded climate estimates for mean annual precipitation, mean annual air temperature, growing degree-days > 0 °C, and photosynthetically active radiation integrated over days > 0 °C. There are significantly shallower depths in permafrost peatlands. Vertical peat accumulation was likely constrained by temperature, growing season length, and photosynthetically active radiation over the last 2 ka in the Hudson Bay Lowlands and surrounding regions.US National Science Foundatio