Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy
Introduction: Preterm birth rates and maternal and neonatal mortality remain concerning global health issues, necessitating improved strategies for testing therapeutic compounds during pregnancy. Current 2D or 3D cell models and animal models often fail to provide data that can effectively translate...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1241815/full |
| _version_ | 1828717490980519936 |
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| author | Ananth K. Kammala Lauren S. Richardson Enkhtuya Radnaa Arum Han Arum Han Ramkumar Menon |
| author_facet | Ananth K. Kammala Lauren S. Richardson Enkhtuya Radnaa Arum Han Arum Han Ramkumar Menon |
| author_sort | Ananth K. Kammala |
| collection | DOAJ |
| description | Introduction: Preterm birth rates and maternal and neonatal mortality remain concerning global health issues, necessitating improved strategies for testing therapeutic compounds during pregnancy. Current 2D or 3D cell models and animal models often fail to provide data that can effectively translate into clinical trials, leading to pregnant women being excluded from drug development considerations and clinical studies. To address this limitation, we explored the utility of in silico simulation modeling and microfluidic-based organ-on-a-chip platforms to assess potential interventional agents.Methods: We developed a multi-organ feto-maternal interface on-chip (FMi-PLA-OOC) utilizing microfluidic channels to maintain intercellular interactions among seven different cell types (fetal membrane-decidua-placenta). This platform enabled the investigation of drug pharmacokinetics in vitro. Pravastatin, a model drug known for its efficacy in reducing oxidative stress and inflammation during pregnancy and currently in clinical trials, was used to test its transfer rate across both feto-maternal interfaces. The data obtained from FMi-PLA-OOC were compared with existing data from in vivo animal models and ex vivo placenta perfusion models. Additionally, we employed mechanistically based simulation software (Gastroplus®) to predict pravastatin pharmacokinetics in pregnant subjects based on validated nonpregnant drug data.Results: Pravastatin transfer across the FMi-PLA-OOC and predicted pharmacokinetics in the in silico models were found to be similar, approximately 18%. In contrast, animal models showed supraphysiologic drug accumulation in the amniotic fluid, reaching approximately 33%.Discussion: The results from this study suggest that the FMi-PLA-OOC and in silico models can serve as alternative methods for studying drug pharmacokinetics during pregnancy, providing valuable insights into drug transport and metabolism across the placenta and fetal membranes. These advanced platforms offer promising opportunities for safe, reliable, and faster testing of therapeutic compounds, potentially reducing the number of pregnant women referred to as “therapeutic orphans” due to the lack of consideration in drug development and clinical trials. By bridging the gap between preclinical studies and clinical trials, these approaches hold great promise in improving maternal and neonatal health outcomes. |
| first_indexed | 2024-03-12T14:28:09Z |
| format | Article |
| id | doaj.art-31e0bc1b54344874854f1e6c97a1f68f |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-12T14:28:09Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-31e0bc1b54344874854f1e6c97a1f68f2023-08-17T19:28:10ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-08-011410.3389/fphar.2023.12418151241815Microfluidic technology and simulation models in studying pharmacokinetics during pregnancyAnanth K. Kammala0Lauren S. Richardson1Enkhtuya Radnaa2Arum Han3Arum Han4Ramkumar Menon5Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, United StatesDivision of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, United StatesDivision of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, United StatesDepartment of Electrical and Computer Engineering, Texas A&M University, College Station, TX, United StatesDepartment of Biomedical Engineering, Texas A&M University, College Station, TX, United StatesDivision of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, United StatesIntroduction: Preterm birth rates and maternal and neonatal mortality remain concerning global health issues, necessitating improved strategies for testing therapeutic compounds during pregnancy. Current 2D or 3D cell models and animal models often fail to provide data that can effectively translate into clinical trials, leading to pregnant women being excluded from drug development considerations and clinical studies. To address this limitation, we explored the utility of in silico simulation modeling and microfluidic-based organ-on-a-chip platforms to assess potential interventional agents.Methods: We developed a multi-organ feto-maternal interface on-chip (FMi-PLA-OOC) utilizing microfluidic channels to maintain intercellular interactions among seven different cell types (fetal membrane-decidua-placenta). This platform enabled the investigation of drug pharmacokinetics in vitro. Pravastatin, a model drug known for its efficacy in reducing oxidative stress and inflammation during pregnancy and currently in clinical trials, was used to test its transfer rate across both feto-maternal interfaces. The data obtained from FMi-PLA-OOC were compared with existing data from in vivo animal models and ex vivo placenta perfusion models. Additionally, we employed mechanistically based simulation software (Gastroplus®) to predict pravastatin pharmacokinetics in pregnant subjects based on validated nonpregnant drug data.Results: Pravastatin transfer across the FMi-PLA-OOC and predicted pharmacokinetics in the in silico models were found to be similar, approximately 18%. In contrast, animal models showed supraphysiologic drug accumulation in the amniotic fluid, reaching approximately 33%.Discussion: The results from this study suggest that the FMi-PLA-OOC and in silico models can serve as alternative methods for studying drug pharmacokinetics during pregnancy, providing valuable insights into drug transport and metabolism across the placenta and fetal membranes. These advanced platforms offer promising opportunities for safe, reliable, and faster testing of therapeutic compounds, potentially reducing the number of pregnant women referred to as “therapeutic orphans” due to the lack of consideration in drug development and clinical trials. By bridging the gap between preclinical studies and clinical trials, these approaches hold great promise in improving maternal and neonatal health outcomes.https://www.frontiersin.org/articles/10.3389/fphar.2023.1241815/fullorgan on chipsimulation modeldrug transportation and pregnancy pharmacokineticsPBPKpregnancy modeling pregnancy pharmacokinetics by microfluidicssimulation |
| spellingShingle | Ananth K. Kammala Lauren S. Richardson Enkhtuya Radnaa Arum Han Arum Han Ramkumar Menon Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy Frontiers in Pharmacology organ on chip simulation model drug transportation and pregnancy pharmacokinetics PBPK pregnancy modeling pregnancy pharmacokinetics by microfluidics simulation |
| title | Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy |
| title_full | Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy |
| title_fullStr | Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy |
| title_full_unstemmed | Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy |
| title_short | Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy |
| title_sort | microfluidic technology and simulation models in studying pharmacokinetics during pregnancy |
| topic | organ on chip simulation model drug transportation and pregnancy pharmacokinetics PBPK pregnancy modeling pregnancy pharmacokinetics by microfluidics simulation |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1241815/full |
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