Exosomal delivery of IL-10: Biodistribution, pharmacokinetics, and preterm birth prevention strategies
This study investigates the potential of extracellular vesicles (EVs) loaded with interleukin-10 (IL-10) to reduce infection-induced preterm birth (PTB). IL-10 has shown promise in reducing PTB by dampening inflammatory responses, but challenges exist with intraamniotic administration. The study eva...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Extracellular Vesicle |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2773041725000022 |
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| author | Brinley Harrington Tilu Jain Thomas Madhuri Tatiparthy Awanit Kumar Lauren Richardson Ramkumar Menon Ananth Kumar Kammala |
| author_facet | Brinley Harrington Tilu Jain Thomas Madhuri Tatiparthy Awanit Kumar Lauren Richardson Ramkumar Menon Ananth Kumar Kammala |
| author_sort | Brinley Harrington |
| collection | DOAJ |
| description | This study investigates the potential of extracellular vesicles (EVs) loaded with interleukin-10 (IL-10) to reduce infection-induced preterm birth (PTB). IL-10 has shown promise in reducing PTB by dampening inflammatory responses, but challenges exist with intraamniotic administration. The study evaluates IL-10 gene-transfected cell-produced EVs containing IL-10 (tIL-10), comparing them with recombinant IL-10 (rIL-10) and rIL-10 incorporated in EVs via electroporation (eIL-10). Characterization of tIL-10 includes size, shape, and molecular markers. Functional assays demonstrate tIL-10's ability to reduce pro-inflammatory cytokine production and extend half-life, with biodistribution in maternal and fetal tissues. The study findings indicate that tIL-10 displays an average size of 108.7 ± 20.5 nm, round with a diameter of ∼0.12 μm, and expresses EV markers CD9 and CD81, containing IL-10 cargo. In vitro, LPS stimulation demonstrates that tIL-10 significantly reduces the production of pro-inflammatory cytokines IL-6 and IL-8 from maternal decidual cells. Biodistribution studies reveal tIL-10 presence in placental and fetal membranes within 5 min, persisting for up to 3 h. Pharmacokinetic studies using non-compartmental analysis of plasma data, and the linear trapezoidal method establish key pharmacologic parameters for each drug. Pharmacological findings establish eIL-10 and tIL-10's ability to significantly delay PTB onset after E. coli exposure. These findings underscore the potential of tIL-10 as an effective therapeutic agent for PTB, with implications for clinical practice and further research in reproductive pharmacology. |
| format | Article |
| id | doaj-art-eefeb972211a4ddda4620f7b22a27fc1 |
| institution | OA Journals |
| issn | 2773-0417 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Extracellular Vesicle |
| spelling | doaj-art-eefeb972211a4ddda4620f7b22a27fc12025-08-20T02:06:12ZengElsevierExtracellular Vesicle2773-04172025-06-01510006610.1016/j.vesic.2025.100066Exosomal delivery of IL-10: Biodistribution, pharmacokinetics, and preterm birth prevention strategiesBrinley Harrington0Tilu Jain Thomas1Madhuri Tatiparthy2Awanit Kumar3Lauren Richardson4Ramkumar Menon5Ananth Kumar Kammala6Division of Basic Science and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, TX, USADivision of Basic Science and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, TX, USADivision of Basic Science and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, TX, USADivision of Basic Science and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, TX, USADivision of Basic Science and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, TX, USACorresponding author. Department of Obstetrics and Gynecology, Mildred Harvey and Phyllis Hankins Maternal Fetal Medicine Distinguished Chair, Division of Basic Science and Translational Research, The University of Texas Medical Branch at Galveston, MRB 11-138, 301, University Blvd, Galveston, TX, 77555, USA.; Division of Basic Science and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, TX, USACorresponding author. Department of Obstetrics and Gynecology, Division of Basic Science and Translational Research, The University of Texas Medical Branch at Galveston, MRB 11-138, 301, University Blvd, Galveston, TX, 77555, USA.; Division of Basic Science and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, TX, USAThis study investigates the potential of extracellular vesicles (EVs) loaded with interleukin-10 (IL-10) to reduce infection-induced preterm birth (PTB). IL-10 has shown promise in reducing PTB by dampening inflammatory responses, but challenges exist with intraamniotic administration. The study evaluates IL-10 gene-transfected cell-produced EVs containing IL-10 (tIL-10), comparing them with recombinant IL-10 (rIL-10) and rIL-10 incorporated in EVs via electroporation (eIL-10). Characterization of tIL-10 includes size, shape, and molecular markers. Functional assays demonstrate tIL-10's ability to reduce pro-inflammatory cytokine production and extend half-life, with biodistribution in maternal and fetal tissues. The study findings indicate that tIL-10 displays an average size of 108.7 ± 20.5 nm, round with a diameter of ∼0.12 μm, and expresses EV markers CD9 and CD81, containing IL-10 cargo. In vitro, LPS stimulation demonstrates that tIL-10 significantly reduces the production of pro-inflammatory cytokines IL-6 and IL-8 from maternal decidual cells. Biodistribution studies reveal tIL-10 presence in placental and fetal membranes within 5 min, persisting for up to 3 h. Pharmacokinetic studies using non-compartmental analysis of plasma data, and the linear trapezoidal method establish key pharmacologic parameters for each drug. Pharmacological findings establish eIL-10 and tIL-10's ability to significantly delay PTB onset after E. coli exposure. These findings underscore the potential of tIL-10 as an effective therapeutic agent for PTB, with implications for clinical practice and further research in reproductive pharmacology.http://www.sciencedirect.com/science/article/pii/S2773041725000022IL-10BioequivalencePregnancyAscending infectionTransfectionElectroporation |
| spellingShingle | Brinley Harrington Tilu Jain Thomas Madhuri Tatiparthy Awanit Kumar Lauren Richardson Ramkumar Menon Ananth Kumar Kammala Exosomal delivery of IL-10: Biodistribution, pharmacokinetics, and preterm birth prevention strategies Extracellular Vesicle IL-10 Bioequivalence Pregnancy Ascending infection Transfection Electroporation |
| title | Exosomal delivery of IL-10: Biodistribution, pharmacokinetics, and preterm birth prevention strategies |
| title_full | Exosomal delivery of IL-10: Biodistribution, pharmacokinetics, and preterm birth prevention strategies |
| title_fullStr | Exosomal delivery of IL-10: Biodistribution, pharmacokinetics, and preterm birth prevention strategies |
| title_full_unstemmed | Exosomal delivery of IL-10: Biodistribution, pharmacokinetics, and preterm birth prevention strategies |
| title_short | Exosomal delivery of IL-10: Biodistribution, pharmacokinetics, and preterm birth prevention strategies |
| title_sort | exosomal delivery of il 10 biodistribution pharmacokinetics and preterm birth prevention strategies |
| topic | IL-10 Bioequivalence Pregnancy Ascending infection Transfection Electroporation |
| url | http://www.sciencedirect.com/science/article/pii/S2773041725000022 |
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