Evaluating applicability domain of acute toxicity QSAR models for military and industrial chemical risk assessment.

Quantitative Structure-Activity Relationship (QSAR) models can be used to predict the risk of novel and emergent chemicals causing adverse health outcomes, avoidance of which is crucial for military operations. While QSAR modeling approaches have been proposed for military and industry risk assessment, the applicability of peer-reviewed tissue-specific QSAR models in military and industrial contexts remain largely unexplored, particularly with respect to specific organ toxicity. We investigated the applicability domain (AD) of acute and sub-chronic tissue-specific QSAR models to evaluate the coverage of military- and industrial-relevant chemicals.

A Comparative Evaluation of Desoximetasone Cream and Ointment Formulations Using Experiments and In Silico Modeling.

The administration of therapeutic drugs through dermal routes, such as creams and ointments, has emerged as an increasingly popular alternative to traditional delivery methods, such as tablets and injections. In the context of drug development, it is crucial to identify the optimal doses and delivery routes that ensure successful outcomes. Physiologically based pharmacokinetic (PBPK) models have been proposed to simulate drug delivery and optimize drug formulations, but the calibration of these models is challenging due to the multitude of variables involved and limited experimental data.

Quercetin and Related Analogs as Therapeutics to Promote Tissue Repair.

Quercetin is a polyphenol of the flavonoid class of secondary metabolites that is widely distributed in the plant kingdom. Quercetin has been found to exhibit potent bioactivity in the areas of wound healing, neuroprotection, and anti-aging research. Naturally found in highly glycosylated forms, aglycone quercetin has low solubility in aqueous environments, which has heavily limited its clinical applications.

Computational Model of In Vivo Corneal Pharmacokinetics and Pharmacodynamics of Topically Administered Ophthalmic Drug Products.

Introduction: Although the eye is directly accessible on the surface of the human body, drug delivery can be extremely challenging due to the presence of multiple protective barriers in eye tissues. Researchers have developed complex formulation strategies to overcome these barriers to ophthalmic drug delivery. Current development strategies rely heavily on in vitro experiments and animal testing to predict human pharmacokinetics (PK) and pharmacodynamics (PD).

A multi-organ chip with matured tissue niches linked by vascular flow.

Engineered tissues can be used to model human pathophysiology and test the efficacy and safety of drugs. Yet, to model whole-body physiology and systemic diseases, engineered tissues with preserved phenotypes need to physiologically communicate. Here we report the development and applicability of a tissue-chip system in which matured human heart, liver, bone and skin tissue niches are linked by recirculating vascular flow to allow for the recapitulation of interdependent organ functions.

Microneedle and iontophoresis mediated delivery of methotrexate into and across healthy and psoriatic skin.

Psoriasis is a condition of the skin which involves scales, dry patches, and inflammation. Methotrexate (logP: -1.8, MW:454.

Microneedle Mediated Iontophoretic Delivery of Tofacitinib Citrate.

Purpose: To investigate in vitro transdermal delivery of tofacitinib citrate across human skin using microporation by microneedles and iontophoresis alone and in combination.

Methods: In vitro permeation studies were conducted using vertical Franz diffusion cells. Microneedles composed of polyvinyl alcohol and carboxymethyl cellulose were fabricated and successfully characterized using scanning electron microscopy.

An integrated biophysical model for predicting the clinical pharmacokinetics of transdermally delivered compounds.

The delivery of therapeutic drugs through the skin is a promising alternative to oral or parenteral delivery routes because dermal drug delivery systems (DSs) offer unique advantages, such as controlled drug release over sustained periods and a significant reduction in first-pass effects, thus reducing the required dosing frequency and the level of patient noncompliance. Furthermore, DSs find applications in multiple therapeutic areas, including drug repurposing. This article presents an integrated biophysical model of dermal absorption for simulating the permeation and absorption of compounds delivered transdermally.

Computational framework for predictive PBPK-PD-Tox simulations of opioids and antidotes.

The primary goal of this work was to develop a computational tool to enable personalized prediction of pharmacological disposition and associated responses for opioids and antidotes. Here we present a computational framework for physiologically-based pharmacokinetic (PBPK) modeling of an opioid (morphine) and an antidote (naloxone). At present, the model is solely personalized according to an individual's mass.

Type of endothelial cells affects HepaRG cell acetaminophen metabolism in both 2D and 3D porous scaffold cultures.

Recent advances in developing in vitro tissue models show that function of hepatocytes is altered in when cultured in 3D configuration and co-culturing with various non-parenchymal cells. However, tissue source for such non-parenchymal cells on viability and metabolic products of hepatocytes have not been explored. In this study, we evaluated the effect of 2D and 3D cultures either with HepaRG cells alone or in combination with liver sinusoidal endothelial cells (LSECs) and human umbilical vein ECs (HUVECs).