Ability of mathematical models to predict human in vivo percutaneous penetration of steroids

Objectives: Liposomes are reported as penetration enhancers for dermal and transdermal delivery. However, little is known about their percutaneous penetration and as to at which level they deliver encapsulated drugs. The penetration of multilamellar vesicles (MLVs) and small unilamellar vesicles (SUVs), in comparison to one of their lipid components, was investigated. Methods: Using the fluorescent lipid, Lissamine Rhodamine B-PE (R), as a constituent, MLV and SUV liposomes were prepared, tested, and R, MLV, or SUV were applied in vivo on the back of hairless mice. Absorption of each was evaluated at the levels of stratum corneum, living skin, and blood by fluorometry. Results: Penetration of the lipid R in stratum corneum in the nonliposomal form exceeded that in the liposomal form and only R penetrates the living skin in a statistically significant manner. No statistical significant absorption into blood was observed with either form. Conclusions: Liposomes size did not play an important role in penetration to stratum corneum. The lipid constituent in the nonliposomal form penetrated at higher rates into stratum corneum and living skin. Even though these liposomes entered stratum corneum, they were not significantly absorbed into viable skin or blood.

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Various Mathematical Models Towards Assessment of the Cardiac Consequences of Drug Combinations and Multiple-currents Inhibition: In Silico Study to Predict In Vivo Effects

Journal of Pharmacological and Toxicological Methods ◽

10.1016/j.vascn.2017.09.140 ◽

2017 ◽

Vol 88 ◽

pp. 211

Author(s):

Barbara Wisniowska ◽

Jakub Szlek ◽

Aleksander Mendyk ◽

Sebastian Polak

Keyword(s):

Mathematical Models ◽

In Silico ◽

Drug Combinations ◽

In Silico Study ◽

In Vivo Effects

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Multi-scale modeling of drug binding kinetics to predict drug efficacy

Cellular and Molecular Life Sciences ◽

10.1007/s00018-019-03376-y ◽

2019 ◽

Vol 77 (3) ◽

pp. 381-394 ◽

Cited By ~ 4

Author(s):

Fabrizio Clarelli ◽

Jingyi Liang ◽

Antal Martinecz ◽

Ines Heiland ◽

Pia Abel zur Wiesch

Keyword(s):

Mathematical Models ◽

Drug Efficacy ◽

Drug Binding ◽

Binding Kinetics ◽

Multi Scale ◽

Drug Concentrations ◽

Body Compartments ◽

Target Binding

AbstractOptimizing drug therapies for any disease requires a solid understanding of pharmacokinetics (the drug concentration at a given time point in different body compartments) and pharmacodynamics (the effect a drug has at a given concentration). Mathematical models are frequently used to infer drug concentrations over time based on infrequent sampling and/or in inaccessible body compartments. Models are also used to translate drug action from in vitro to in vivo conditions or from animal models to human patients. Recently, mathematical models that incorporate drug-target binding and subsequent downstream responses have been shown to advance our understanding and increase predictive power of drug efficacy predictions. We here discuss current approaches of modeling drug binding kinetics that aim at improving model-based drug development in the future. This in turn might aid in reducing the large number of failed clinical trials.

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