Journal of Chromatography B, Год журнала: 2025, Номер unknown, С. 124695 - 124695
Опубликована: Июнь 1, 2025
Язык: Английский
ACS Nano, Год журнала: 2023, Номер 17(15), С. 14205 - 14228
Опубликована: Июль 27, 2023
The use of nanoparticles (NPs) in nanomedicine holds great promise for the treatment diseases which conventional therapies present serious limitations. Additionally, NPs can drastically improve early diagnosis and follow-up many disorders. However, to harness their full capabilities, they must be precisely designed, produced, tested relevant models. Microfluidic systems simulate dynamic fluid flows, gradients, specific microenvironments, multiorgan complexes, providing an efficient cost-effective approach both synthesis screening. technologies allow under controlled conditions, enhancing batch-to-batch reproducibility. Moreover, due versatility microfluidic devices, it is possible generate customize endless platforms rapid vitro vivo screening NPs' performance. Indeed, devices show potential as advanced small organism manipulation immobilization. In this review, first we summarize major that synthesis. Next, will discuss most innovative enable mimicking environments well give insights into organism-on-a-chip promising application We conclude review with a critical assessment current challenges future directions impact field nanomedicine.
Язык: Английский
Процитировано
126
Materials Today Bio, Год журнала: 2024, Номер 27, С. 101143 - 101143
Опубликована: Июль 2, 2024
Recent FDA modernization act 2.0 has led to increasing industrial R&D investment in advanced
Язык: Английский
Процитировано
11
PLoS ONE, Год журнала: 2025, Номер 20(1), С. e0314083 - e0314083
Опубликована: Янв. 9, 2025
Digital twins, driven by data and mathematical modelling, have emerged as powerful tools for simulating complex biological systems. In this work, we focus on modelling the clearance a liver-on-chip digital twin that closely mimics functionality of human liver. Our approach involves creation compartmental physiological model liver using ordinary differential equations (ODEs) to estimate pharmacokinetic (PK) parameters related on-chip clearance. The objectives study were twofold: first, predict values, second, propose framework bridging gap between in vitro findings their clinical relevance. methodology integrated quantitative Organ-on-Chip (OoC) cell-based assay analyses drug depletion kinetics is further enhanced incorporating an OoC-digital simulate humans. 32 drugs was predicted digital-twin vivo extrapolation (IVIVE) assessed time series PK data. Three ODEs define concentrations media, interstitium intracellular compartments based biological, hardware, physicochemical information. A key issue determining appears be insufficient concentration within compartment. establishes connection hardware chip structure advanced mapping underlying biology, specifically focusing offers following benefits: i ) better prediction intrinsic compared conventional ii )explainability behaviour parameters. Finally, illustrate significance applying humans, utilising propranolol proof-of-concept example. This stands out biggest cross-organ-on-chip platform investigation date, systematically analysing predicting values obtained from various Accurate important inadequate understanding compound can lead unexpected undesirable outcomes trials, ranging underdosing toxicity. Physiologically (PBPK) estimation explored. aim develop twins capable predictions outcomes, ultimately reducing time, cost, patient burden associated with development. Various hepatic systems are effectiveness investigated. developed tool, DigiLoCs, focuses explicitly accurately describing processes liver-chip ODE-constrained optimisation applied compounds. DigiLoCs enable differentiation active (metabolism) passive (permeability partitioning) detailed information compound-specific characteristics hardware-specific These signify significant stride towards more accurate efficient development methodologies.
Язык: Английский
Процитировано
2
Lab on a Chip, Год журнала: 2022, Номер 22(15), С. 2853 - 2868
Опубликована: Янв. 1, 2022
Microphysiological systems (MPS) consisting of multiple linked organ-on-a-chip (OoC) components are highly promising tools with potential to provide more relevant in vitro vivo translation drug disposition, efficacy and toxicity. A gut-liver OoC system was employed Caco2 cells co-culture HT29 the intestinal compartment single donor primary hepatocytes hepatic for investigation permeability, metabolism (intestinal hepatic) interplay those processes. The prodrug mycophenolate mofetil tested quantitative evaluation due contribution both gut liver its metabolism. Conversion active mycophenolic acid further a glucuronide metabolite assessed over time apical, basolateral compartments. Mechanistic modelling experimental data performed estimate clearance permeability parameters prodrug, metabolite. Integration silico allowed complex combination processes, which is not possible standard tissue systems. comprehensive mechanistic model, including structural model parameter identifiability global sensitivity analysis, enabled robust design estimation pharmacokinetic parameters. We propose that similar methodologies may be applied other multi-organ microphysiological used studies or wherever knowledge changing concentration enables better understanding biological effect.
Язык: Английский
Процитировано
38
AJP Gastrointestinal and Liver Physiology, Год журнала: 2022, Номер 323(3), С. G188 - G204
Опубликована: Июль 12, 2022
Physiologically relevant and broadly applicable liver cell culture platforms are of great importance in both drug development disease modeling. Organ-on-a-chip systems offer a promising alternative to conventional, static two-dimensional (2-D) cultures, providing much-needed cues such as perfusion, shear stress, three-dimensional (3-D) cell-cell communication. However, devices cover broad range complexity manufacture implementation. In this review, we summarize the key features human that should be reflected physiologically liver-on-a-chip model. We also discuss different material properties producing recent current progress field, highlighting types at levels complexity.
Язык: Английский
Процитировано
30
Pharmacological Research, Год журнала: 2023, Номер 195, С. 106853 - 106853
Опубликована: Июль 18, 2023
Organ-on-chip (OoC) technology has led to in vitro models with many new possibilities compared conventional and vivo models. In this review, the potential of OoC improve prediction human oral bioavailability intrinsic clearance is discussed, a focus on functionality application current drug development practice. Multi-OoC demonstrating for pharmacokinetic (PK) studies are summarized existing challenges identified. Physiological parameters minimal viable platform multi-OoC model study PK provided, together specific read-outs recommendations relevant reference compounds validate model. Finally, translation profiles which will be required routinely apply during development.
Язык: Английский
Процитировано
18
Micromachines, Год журнала: 2024, Номер 15(7), С. 873 - 873
Опубликована: Июнь 30, 2024
The evolution in the biomedical engineering field boosts innovative technologies, with microfluidic systems standing out as transformative tools disease diagnosis, treatment, and monitoring. Numerical simulation has emerged a tool of increasing importance for better understanding predicting fluid-flow behavior microscale devices. This review explores fabrication techniques common materials devices, focusing on soft lithography additive manufacturing. Microfluidic applications, including nucleic acid amplification protein synthesis, well point-of-care diagnostics, DNA analysis, cell cultures, organ-on-a-chip models (e.g., lung-, brain-, liver-, tumor-on-a-chip), are discussed. Recent studies have applied computational such ANSYS Fluent 2024 software to numerically simulate flow behavior. Outside study cases, this work reports fundamental aspects simulations, fluid flow, mass transport, mixing, diffusion, highlights emergent simulations. Additionally, it takes into account application geometries improve mixing samples, surface wettability modification. In conclusion, present summarizes most relevant contributions their numerical modeling engineering.
Язык: Английский
Процитировано
8
Frontiers in Pharmacology, Год журнала: 2025, Номер 16
Опубликована: Фев. 12, 2025
Background Pregnant women represent a vulnerable group in pharmaceutical research due to limited knowledge about drug metabolism and safety of commonly used corticosteroids like prednisone ethical practical constraints. Current preclinical models, including animal studies, fail accurately replicate human pregnancy conditions, resulting gaps pharmacokinetics predictions. To address this issue, we three-organ microphysiological system (MPS) combined with digital twin framework, predict fetal exposure. Methods The here shown MPS integrated gut, liver, placenta interconnected via the corresponding vasculature. Using as model compound, simulate oral administration track its transplacental transfer. translate generated data from physiology, computational modelling techniques were developed. Results Our results demonstrate that maintains cellular integrity mimics vivo dynamics, predictions closely matching clinical pregnant women. Digital twinning aligned experimental data. Long-term exposure simulations confirmed value for predicting non-toxic metabolization prednisone. Conclusion This approach may provide potential non-animal alternative could contribute our understanding behavior during support early-stage assessment populations.
Язык: Английский
Процитировано
1
The AAPS Journal, Год журнала: 2023, Номер 25(6)
Опубликована: Окт. 27, 2023
Abstract A crucial step in lead selection during drug development is accurate estimation and optimization of hepatic clearance using vitro methods. However, current methods are limited by factors such as lack physiological relevance, short culture/incubation times that not consistent with exposure patterns patients, use absorbing materials, evaporation long-term incubation. To address these technological needs, we developed a novel milli-fluidic human liver tissue chip (LTC) was designed continuous media recirculation optimized for cultures primary hepatocytes. Here, characterized the LTC series physiologically relevant metrics test compounds to demonstrate could accurately predict PK both low- high-clearance compounds. The non-biological characterization indicated cyclic olefin copolymer (COC)–based exhibited negligible minimal non-specific binding drugs varying ionic states lipophilicity. Biologically, functional polarized culture sustained metabolic CYP activity at least 15 days. This then used studies 12 days, estimated range high - vivo correlation (IVIVC). We also demonstrated can be induced rifampicin, age had insignificant effect on depletion kinetic predicted value. Thus, advances bioengineering develop purpose-built platform reproducibility variability unmet needs applications. Graphical
Язык: Английский
Процитировано
16
Biofabrication, Год журнала: 2024, Номер 16(4), С. 042006 - 042006
Опубликована: Авг. 27, 2024
Abstract Recent years have seen the creation and popularization of various complex in vitro models (CIVMs), such as organoids organs-on-chip, a technology with potential to reduce animal usage pharma while also enhancing our ability create safe efficacious drugs for patients. Public awareness CIVMs has increased, part, due recent passage FDA Modernization Act 2.0. This visibility is expected spur deeper investment adoption models. Thus, end-users model developers alike require framework both understand readiness current enter drug development process, assess upcoming same. review presents selection based on comparative -omics data (which we term model-omics), metrics qualification specific test assays that may support context-of-use (COU) assays. We surveyed existing healthy tissue ten development-critical organs body, provide evaluations suggestions improving model-omics COU each. In whole, this comes from perspective, seeks an evaluation where are poised maximum impact roadmap realizing potential.
Язык: Английский
Процитировано
6