Simulation-based approaches for drug delivery systems: Navigating advancements, opportunities, and challenges

Journal of Molecular Liquids, Journal Year: 2023, Volume and Issue: 395, P. 123888 - 123888

Published: Dec. 27, 2023

Efficient drug delivery systems (DDSs) play a pivotal role in ensuring pharmaceuticals' targeted and effective administration. However, the intricate interplay between formulations poses challenges their design optimization. Simulations have emerged as indispensable tools for comprehending these interactions enhancing DDS performance to address this complexity. This comprehensive review explores latest advancements simulation techniques provides detailed analysis. The encompasses various methodologies, including molecular dynamics (MD), Monte Carlo (MC), finite element analysis (FEA), computational fluid (CFD), density functional theory (DFT), machine learning (ML), dissipative particle (DPD). These are critically examined context of research. article presents illustrative case studies involving liposomal, polymer-based, nano-particulate, implantable DDSs, demonstrating influential simulations optimizing systems. Furthermore, addresses advantages limitations It also identifies future directions research development, such integrating multiple techniques, refining validating models greater accuracy, overcoming limitations, exploring applications personalized medicine innovative DDSs. employing like MD, MC, FEA, CFD, DFT, ML, DPD offer crucial insights into behaviour, aiding Despite advantages, rapid cost-effective screening, require validation addressing limitations. Future should focus on models, enhance outcomes. paper underscores contribution emphasizing providing valuable facilitating development optimization ultimately patient As we continue explore impact advancing discovery improving DDSs is expected be profound.

Language: Английский

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Removal of ciprofloxacin lactate by phosphoric acid activated biochar: Urgent consideration of new antibiotics for human health

Chemical Engineering Science, Journal Year: 2023, Volume and Issue: 283, P. 119403 - 119403

Published: Oct. 17, 2023

Language: Английский

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A guide to the use of bioassays in exploration of natural resources

Biotechnology Advances, Journal Year: 2024, Volume and Issue: 71, P. 108307 - 108307

Published: Jan. 5, 2024

Bioassays are the main tool to decipher bioactivities from natural resources thus their selection and quality critical for optimal bioprospecting. They used both in early stages of compounds isolation/purification/identification, later evaluate safety efficacy. In this review, we provide a comprehensive overview most common bioassays discovery development new bioactive with focus on marine bioresources. We present list practical considerations selecting appropriate discuss detail typically explore antimicrobial, antibiofilm, cytotoxic, antiviral, antioxidant, anti-ageing potential. The concept control bioassay validation introduced, followed by considerations, which advancing higher stage development. conclude providing an application-oriented view focused pharmaceuticals, food supplements, cosmetics, industrial pipelines where currently known products hold highlight importance gaining reliable results, as these serve starting point application-based further testing, well consideration regulatory authorities.

Language: Английский

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Chemical risk assessment in food animals via physiologically based pharmacokinetic modeling − Part I: Veterinary drugs on human food safety assessment

Environment International, Journal Year: 2025, Volume and Issue: 197, P. 109339 - 109339

Published: Feb. 18, 2025

Language: Английский

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Nuclear hormone receptors control fundamental processes of human fetal neurodevelopment: Basis for endocrine disruption assessment

Environment International, Journal Year: 2025, Volume and Issue: 198, P. 109400 - 109400

Published: March 21, 2025

Despite growing awareness of endocrine disrupting chemicals (EDCs), knowledge gaps remain regarding their effects on human brain development. EDC risk assessment focuses primarily EATS modalities (estrogens, androgens, thyroid hormones, and steroidogenesis), overlooking the broader range hormone receptors expressed in developing brain. This limits evaluation for potential to cause disruption-mediated developmental neurotoxicity (ED-DNT). The Neurosphere Assay, an vitro test method (DNT) evaluation, is integral component DNT testing battery, which has been used screen a broad domain environmental chemicals. Here, we define endocrine-related applicability Assay by assessing impact specificity 14 seven key neurodevelopmental processes (KNDPs), neural progenitor cell (NPC) proliferation, migration radial glia, neurons, oligodendrocytes, neurite outgrowth, differentiation neurons oligodendrocytes. Comparative analyses rat NPCs both sexes revealed species- sex-specific responses. Mechanistic insights were obtained through RNA sequencing agonist/antagonist co-exposures. Most receptor agonists modulated KNDPs at concentrations physiologically relevant concentrations. Phenotypic induced glucocorticoid (GR), liver X (LXR), peroxisome proliferator-activated beta/delta (PPARβδ), retinoic acid (RAR) retinoid (RXR) activation counteracted antagonists, confirming specificity. Transcriptomics highlighted crosstalk involvement conserved pathways (e.g. Notch Wnt). Species comparisons identified limited concordance receptor-regulated between NPCs. study presents novel findings cellular molecular actions fetal NPCs, highlights major species differences, illustrates Assay's relevance detecting MoAs, supporting its application human-based ED-DNT assessment.

Language: Английский

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Next Generation Risk Assessment of Hair Dye HC Yellow No. 13: Ensuring Protection From Liver Steatogenic Effects

Regulatory Toxicology and Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 105794 - 105794

Published: Feb. 1, 2025

This study employs animal-free Next Generation Risk Assessment (NGRA) principles to evaluate the safety of repeated dermal exposure 2.5% (w/w) HC Yellow No. 13 (HCY13) hair dye. As multiple in silico tools consistently flagged hepatotoxic potential, likely due HCY13's trifluoromethyl group, which is known interfere with hepatic lipid metabolism, liver steatosis was chosen as primary mode action for evaluation. AOP-guided vitro tests were conducted, exposing human stem cell-derived cells varying HCY13 concentrations over 72 hours. The expression 11 metabolism-related marker genes (AHR, PPARA, LXRA, APOB, ACOX1, CPT1A, FASN, SCD1, DGAT2, CD36, and PPARG) triglyceride accumulation, a phenotypic hallmark steatosis, measured. PROAST software used calculate Points Departure (PoDNAM) each biomarker. Using GastroPlus 9.9, physiologically-based pharmacokinetic (PBPK) models estimated internal (Cmax liver) HCY13, ranging from 4 20 pM. All PoDNAM values significantly exceeded predicted Cmax liver, indicating that at unlikely induce under assumed conditions. research demonstrates utility NGRA, integrating AOP-based assays computational protect health support regulatory decision-making without animal testing.

Language: Английский

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Utility of life stage-specific chemical risk assessments based on New Approach Methodologies (NAMs)

Food and Chemical Toxicology, Journal Year: 2024, Volume and Issue: 190, P. 114789 - 114789

Published: June 5, 2024

Language: Английский

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Worldwide serum concentration-based probabilistic mixture risk assessment of perfluoroalkyl substances among pregnant women, infants, and children

Ecotoxicology and Environmental Safety, Journal Year: 2023, Volume and Issue: 268, P. 115712 - 115712

Published: Nov. 24, 2023

Pregnant women, infants, and children are particularly vulnerable to perfluoroalkyl substances (PFASs), yet little is known about related health risks. Here, we aimed study the four main PFASs: perfluorooctanesulfonic acid (PFOS), perfluorooctanoic (PFOA), perfluorononanoic (PFNA), perfluorohexanesulfonic (PFHxS), assess mixture risks of co-exposure PFASs for pregnant women as well infants associated with maternal PFAS exposure at national global scales, based on biomonitoring data serum. We conducted a literature search aggregated 69 sources across 22 countries/regions from 2010 2020 profile serum concentrations these in children. Based toxicity assessments by regulatory authorities, determined conservative reference levels (RfLs) primary adverse effects PFASs, including hepatic, developmental, immune effects. The cumulative hazard quotient (HQ) was combined probabilistic analysis compare RfLs quantify Our revealed that PFOS dominant child worldwide, median 2.5-10 times higher than those PFOA, PFNA, PFHxS. estimated were 6.17 ng/mL 4.85 children, their concerning HQs could exceed 1. For both developmental also be > 1, suggesting during pregnancy breastfeeding may pose concerns infant development immunity. database risk assessment offer additional insights into exposures susceptible populations, serving evaluating effectiveness ongoing mitigation measures.

Language: Английский

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Recent Progress on Physiologically Based Pharmacokinetic (PBPK) Model: A Review Based on Bibliometrics

Toxics, Journal Year: 2024, Volume and Issue: 12(6), P. 433 - 433

Published: June 14, 2024

Physiologically based pharmacokinetic/toxicokinetic (PBPK/PBTK) models are designed to elucidate the mechanism of chemical compound action in organisms on physiological, biochemical, anatomical, and thermodynamic properties organisms. After nearly a century research practice, good results have been achieved fields medicine, environmental science, ecology. However, there is currently lack more systematic review progress main directions PBPK models, especially comprehensive understanding application aquatic research. In this review, total 3974 articles related from 1996 24 March 2024 were collected. Then, areas model categorized keyword co-occurrence maps cluster obtained by CiteSpace. The showed that medicine area PBPK. Four major included medical field “drug assessment”, “cross-species prediction”, “drug–drug interactions”, “pediatrics pregnancy drug development”, which assessment” accounted for 55% publication volume. addition, bibliometric analyses indicated rapid growth trend research, predicting residual levels revealing relationship between internal external exposure. Despite facing limitation insufficient species-specific parameters, still an effective tool improving chemical–biological effectiveness will provide theoretical basis accurately assessing potential risks ecosystems human health. combination with quantitative structure–activity model, Bayesian method, machine learning technology solutions previous gaps.

Language: Английский

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Toxicokinetics and Modeling

Elsevier eBooks, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

Language: Английский

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