The biorelated degradability and clearance of siliceous nanomaterials have been questioned worldwide, since they are crucial prerequisites for the successful translation in clinics. Typically, the degradability and biocompatibility of mesoporous silica nanoparticles (MSNs) have been an ongoing discussion in research circles. The reason for such a concern is that approved pharmaceutical products must not accumulate in the human body, to prevent severe and unpredictable side-effects. Here, the biorelated degradability and clearance of silicon and silica nanoparticles (NPs) are comprehensively summarized. The influence of the size, morphology, surface area, pore size, and surface functional groups, to name a few, on the degradability of silicon and silica NPs is described. The noncovalent organic doping of silica and the covalent incorporation of either hydrolytically stable or redox- and enzymatically cleavable silsesquioxanes is then described for organosilica, bridged silsesquioxane (BS), and periodic mesoporous organosilica (PMO) NPs. Inorganically doped silica particles such as calcium-, iron-, manganese-, and zirconium-doped NPs, also have radically different hydrolytic stabilities. To conclude, the degradability and clearance timelines of various siliceous nanomaterials are compared and it is highlighted that researchers can select a specific nanomaterial in this large family according to the targeted applications and the required clearance kinetics.

Degradability and Clearance of Silicon, Organosilica, Silsesquioxane, Silica Mixed Oxide, and Mesoporous Silica Nanoparticles.

Porous silicon nanoparticles for nanomedicine: preparation and biomedical applications.

Rapid immune recognition and subsequent elimination from the circulation hampers the use of many nanomaterials as carriers to targeted drug delivery and controlled release in the intravenous route. Here, we report the effect of a functional self-assembled protein coating on the intravenous biodistribution of 18F-labeled thermally hydrocarbonized porous silicon (THCPSi) nanoparticles in rats. 18F-Radiolabeling enables the sensitive and easy quantification of nanoparticles in tissues using radiometric methods and allows imaging of the nanoparticle biodistribution with positron emission tomography. Coating with Trichoderma reesei HFBII altered the hydrophobicity of 18F-THCPSi nanoparticles and resulted in a pronounced change in the degree of plasma protein adsorption to the nanoparticle surface in vitro. The HFBII-THCPSi nanoparticles were biocompatible in RAW 264.7 macrophages and HepG2 liver cells making their intravenous administration feasible. In vivo, the distribution of the nanoparticles between the l...

Intravenous delivery of hydrophobin-functionalized porous silicon nanoparticles: stability, plasma protein adsorption and biodistribution

A multifunctional nano-in-micro drug delivery platform is developed by conjugating the porous silicon nanoparticles with mucoadhesive polymers and subsequent encapsulation into a pH-responsive polymer using microfluidics. The multistage platform shows monodisperse size distribution and pH-responsive payload release, and the released nanoparticles are mucoadhesive. Moreover, this platform is capable of simultaneously loading and releasing multidrugs with distinct properties.

Fabrication of a multifunctional nano-in-micro drug delivery platform by microfluidic templated encapsulation of porous silicon in polymer matrix.

In the past two decades, porous silicon (PSi) has attracted increasing attention for its potential biomedical applications. With its controllable geometry, tunable nanoporous structure, large pore volume/high specific surface area, and versatile surface chemistry, PSi shows significant advantages over conventional drug carriers. Here, an overview of recent progress in the use of PSi in drug delivery and cancer immunotherapy is presented. First, an overview of the fabrication of PSi with various geometric structures is provided, with particular focus on how the unique geometry of PSi facilitates its biomedical applications, especially for drug delivery. Second, surface chemistry and modification of PSi are discussed in relation to the strengthening of its performance in drug delivery and bioimaging. Emerging technologies for engineering PSi-based composites are then summarized. Emerging PSi advances in the context of cancer immunotherapy are also highlighted. Overall, very promising research results encourage further exploration of PSi for biomedical applications, particularly in drug delivery and cancer immunotherapy, and future translation of PSi into clinical applications.

/pdf/tailoring-porous-silicon-for-biomedical-applications-from-4mn3de8z7b.pdf

Tailoring Porous Silicon for Biomedical Applications : From Drug Delivery to Cancer Immunotherapy

Functional hydrophobin-coating of thermally hydrocarbonized porous silicon microparticles

Introduction In patients with peripheral neuropathies (PNP), neuropathic pain is present in 50% of the cases, independent of the etiology. The pathophysiology of pain is poorly understood, and inflammatory processes have been found to be involved in neuro-degeneration, -regeneration and pain. While previous studies have found a local upregulation of inflammatory mediators in patients with PNP, there is a high variability described in the cytokines present systemically in sera and cerebrospinal fluid (CSF). We hypothesized that the development of PNP and neuropathic pain is associated with enhanced systemic inflammation. Methods To test our hypothesis, we performed a comprehensive analysis of the protein, lipid and gene expression of different pro- and anti-inflammatory markers in blood and CSF from patients with PNP and controls. Results While we found differences between PNP and controls in specific cytokines or lipids, such as CCL2 or oleoylcarnitine, PNP patients and controls did not present major differences in systemic inflammatory markers in general. IL-10 and CCL2 levels were related to measures of axonal damage and neuropathic pain. Lastly, we describe a strong interaction between inflammation and neurodegeneration at the nerve roots in a specific subgroup of PNP patients with blood-CSF barrier dysfunction. Conclusion In patients with PNP systemic inflammatory, markers in blood or CSF do not differ from controls in general, but specific cytokines or lipids do. Our findings further highlight the importance of CSF analysis in patients with peripheral neuropathies.

https://www.frontiersin.org/articles/10.3389/fimmu.2023.1067714/pdf

Systemic inflammatory markers in patients with polyneuropathies

Cannabis sativa plants contain a multitude of bioactive substances, which show broad variability between different plant strains. Of the more than a hundred naturally occurring phytocannabinoids, Δ9-Tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) have been the most extensively studied, but whether and how the lesser investigated compounds in plant extracts affect bioavailability or biological effects of Δ9-THC or CBD is not known. We therefore performed a first pilot study to assess THC concentrations in plasma, spinal cord and brain after oral administration of THC compared to medical marijuana extracts rich in THC or depleted of THC. Δ9-THC levels were higher in mice receiving the THC-rich extract. Surprisingly, only orally applied CBD but not THC alleviated mechanical hypersensitivity in the mouse spared nerve injury model, favoring CBD as an analgesic compound for which fewer unwanted psychoactive effects are to be expected.

/pdf/pharmacokinetics-of-orally-applied-cannabinoids-and-medical-n9lu6tlv.pdf

Katharina Strommer

Papers

Functional hydrophobin-coating of thermally hydrocarbonized porous silicon microparticles

Systemic inflammatory markers in patients with polyneuropathies

Pharmacokinetics of Orally Applied Cannabinoids and Medical Marijuana Extracts in Mouse Nervous Tissue and Plasma: Relevance for Pain Treatment