arXiv subjects

Daniel Sebastia-Saez

Publications and source records attributed to Daniel Sebastia-Saez.

5 recordsLinked to original sources

arXiv2024

Advancing glaucoma research with multiphysics continuum mechanics modelling: Opportunities and open challenges

This review examines the emerging role of mechanistic mathematical models based on continuum mechanics to address current challenges in glaucoma research. At present, the advent of Artificial Intelligence and data-based models have resulted in significant progress in drug candidate screening, target identification and delivery optimization for glaucoma treatment. Physics-based models on the other hand offer mechanistic insight by modelling fundamental physical knowledge. Mechanistic models, and specifically those based on continuum mechanics, have the potential to contribute to a better understanding of glaucoma through the description of intraocular fluid dynamics, mass and heat transfer and other basic physical phenomena. So far, these models have expanded our understanding of ocular fluid dynamics, including descriptions of fluid flow profiles within the anterior chamber of the eye under glaucomatous conditions. With the ongoing development of multiphysics modelling frameworks, there is increasing potential to apply these tools to a wide range of current challenges within the field of glaucoma research. These challenges include glaucoma drainage devices, minimally invasive surgical procedures, therapeutic contact lenses, laser-based interventions like peripheral iridotomy, and the design and optimization of biodegradable drug-releasing intracameral implants, which support patient-specific strategies for glaucoma diagnosis and treatment

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arXiv2024

Comparative CFD modelling of the interplay between aqueous humour hydrodynamics and drug and nanocarrier transport for glaucoma drug delivery via intracameral injection, drug-eluting implants and contact lenses

Glaucoma is the leading cause of irreversible blindness worldwide and often requires long-term administration of intraocular pressure-lowering agents. The effectiveness of ocular drug delivery depends not only on the delivery route but also on the transport mechanisms governing drug distribution within the eye. In this study, a computational fluid dynamics (CFD) framework was developed to investigate the influence of aqueous humour hydrodynamics on the transport of dissolved drugs and nanocarriers delivered by three clinically relevant strategies: intracameral injection, drug-eluting implants and contact lenses. An idealised three-dimensional model of the anterior segment was implemented in COMSOL Multiphysics v6.4, incorporating aqueous humour flow, thermal convection, drug transport, saccadic eye movements and particle tracing. This framework enabled direct comparison of molecular diffusion- and particle-mediated delivery. Simulations revealed substantial differences in intraocular transport among the delivery strategies. Contact-lens delivery produced the most homogeneous drug distributions, whereas implant-based delivery generated persistent concentration gradients associated with localised release. Intracameral injection exhibited intermediate behaviour, with rapid redistribution by aqueous humour circulation. Nanocarrier transport showed greater spatial heterogeneity than dissolved-drug transport owing to reduced diffusivity and consequently stronger advection-dominated transport. These findings demonstrate that aqueous humour hydrodynamics are an independent determinant of ocular drug transport and should be considered in the design of sustained ophthalmic drug delivery systems. The proposed framework provides a versatile computational tool for the optimisation of both dissolved-drug and nanocarrier-based glaucoma therapies.

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arXiv2024

In silico study on the contribution of the follicular route to dermal permeability of small molecules

Purpose. This study investigates in silico the contribution of the hair follicle to the overall dermal permeability of small molecules, as published experimental work provides inconclusive information on whether the follicular route favours the permeation of hydrophobic or hydrophilic permeants. Method. A study is conducted varying physico-chemical parameters of permeants such as lipophilicity, molecular weight and protein binding. The simulated data is compared to published experimental data to discuss how those properties can modulate the contribution of the hair follicle to the overall dermal permeation. Results. The results indicate that the contribution of the follicular route to dermal permeation can range from negligible to notable depending on the combination of lipophilic/hydrophilic properties of the substance filling the follicular route and the permeant. Conclusion. Characterisation of the substance filling the follicular route is required for analysing the experimental data of dermal permeation of small molecules, as changes between in vivo and in vitro due to handling of samples and cessation of vital functions can modify the contribution of the follicular route to overall dermal permeation, hence hindering data interpretation.

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arXiv2020

Numerical analysis of the strain distribution in skin domes formed upon the application of hypobaric pressure

Suction cups are widely used in applications such as in measurement of mechanical properties of skin in vivo, in drug delivery devices or in acupuncture treatment. Understanding the mechanical response of skin under hypobaric pressure are of great importance for users of suction cups. The aims of this work are to assess the capability of linear elasticity (Young's modulus) or hyperelasticity in predicting hypobaric pressure induced 3D stretching of the skin. Using experiments and computational Finite Element Method modelling, this work demonstrated that although it was possible to predict the suction dome apex height using both linear elasticity and hyperelasticity for the typical range of hypobaric pressure in medical applications (up to -10 psi), linear elasticity theory showed limitations when predicting the strain distribution across the suction dome. The reason is that the stretch ratio reaches values exceeding the initial linear elastic stage of the stress-strain characteristic curve for skin. As a result, the linear elasticity theory overpredicts the stretch along the rim of domes where there is stress concentration. In addition, the modelling showed that the skin was compressed consistently along the thickness direction, leading to reduced thickness. Using hyperelasticity modelling to predict the 3D strain distribution paves the way to accurately design safe commercial products that interface with skin.

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arXiv2019

New trends in mechanistic transdermal drug delivery modelling: Towards an accurate description of skin microstructure

Interest for in silico modelling of the absorption of xenobiotics into the skin has been growing in the last years, owing to their lower cost compared to experimental alternatives, and the desire to avoid animal experimentation. This review presents an overview of Physiologically-Based Pharmacokinetic (PBPK) models and focuses on recent, modelling approaches, such as Finite Element and Lattice Boltzmann. These methods allow for a detailed geometric representation of the skin microstructure, in contrast to classic QSPR and compartmental models. Morphological features of the skin such as the bricks and mortar description of the stratum corneum, hair follicles, and the pilosebaceous unit can therefore be represented more accurately, allowing a better description of the interaction of cosmetics with the skin. This review also highlights several perspectives to further develop these models in directions relevant to industry.

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