Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA.
Published: October 2023
AI Article Synopsis
Article Abstract
This white paper summarizes the recommendations of the absorption, distribution, metabolism, and excretion (ADME) Subcommittee of the Oligonucleotide Safety Working Group for the characterization of absorption, distribution, metabolism, and excretion of oligonucleotide (ON) therapeutics in nonclinical studies. In general, the recommended approach is similar to that for small molecule drugs. However, some differences in timing and/or scope may be warranted due to the greater consistency of results across ON classes as compared with the diversity among small molecule classes. For some types of studies, a platform-based approach may be appropriate; once sufficient data are available for the platform, presentation of these data should be sufficient to support development of additional ONs of the same platform. These recommendations can serve as a starting point for nonclinical study design and foundation for discussions with regulatory agencies.
Background: Retinal ganglion cell (RGC) death caused by acute ocular hypertension is an important characteristic of acute glaucoma. Receptor-interacting protein kinase 3 (RIPK3) that mediates necroptosis is a potential therapeutic target for RGC death. However, the current understanding of the targeting agents and mechanisms of RIPK3 in the treatment of glaucoma remains limited.
Ablative fractional laser-assisted drug delivery has gained attention as a promising method for enhancing dermal drug absorption and improving therapeutic outcomes in dermatological conditions, particularly for hypertrophic and keloid scars. However, despite the growing number of clinical trials and case reports supporting its efficacy, there remains a scarcity of robust evidence on the topical bioavailability and dermato-pharmacokinetics of drugs in human subjects. This study aimed to examine the enhancement of triamcinolone acetonide (TAC) bioavailability following treatment with a fractional Erbium-Doped Yttrium Aluminum Garnet (Er: YAG) laser.
Objective: To explore the possible mechanism of absorption of iron oxide nanoparticles into the human body through the gastrointestinal tract.
Methods: This article used Caco-2 monolayer cells as a cell model, prepared characterized iron oxide nanoparticles(Fe_2O_3 NPs) as suspensions, and intervened in Caco-2 cells. CCK-8 method, transwell method, and atomic spectrophotometer method were used to explore the effect of Fe_2O_3 NPs on the activity of Caco-2 cells and the absorption and transport of them through the Caco-2 monolayer cell model.
This study investigated the speciation and aqueous dissolution of macronutrients in fire ash from diverse ecosystems and speciation of ash and smoke from laboratory burning, exploring the variations and their causes. The speciation of phosphorus (P), calcium (Ca), and potassium (K) in fire ash from five globally distributed ecosystems was characterized by using X-ray absorption spectroscopy and sequential fractionation. Aqueous dissolution of the macronutrients was measured by batch experiments at acidic and alkaline pHs.
This study investigates the quantities of Rare Earth Elements (REEs) and Potentially Toxic Elements (PTEs) in Dong Nai Province's surface soils. Atomic Absorption Spectrometry (AAS) and Instrumental Neutron Activation Analysis (INAA) were used to determine element concentrations. To validate the concentration results, established reference materials (NIST 2711 and IAEA Soil-7) were used.
