Assessing gut barrier integrity and reproductive performance following pre-mating oral administration of solid-lipid-nanoparticles designed for drug delivery
Solid lipid nanoparticles (SLNs) have gained interest as drug delivery carriers due to their efficient cellular internalization and increased therapeutic effect of the loaded drug, with minimal side effects. Although recently several studies have shown the possibility to administer SLNs during pregn...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Toxicology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/ftox.2024.1508598/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841556879852961792 |
|---|---|
| author | Valentina Lacconi Valentina Lacconi Micol Massimiani Micol Massimiani Giulia Antonello Paolo Gasco Roberta Bernardini Cristiana Ferrari Lorenzo Ippoliti Gina La Sala Antonio Pietroiusti Ivana Fenoglio Chiara Riganti Luisa Campagnolo |
| author_facet | Valentina Lacconi Valentina Lacconi Micol Massimiani Micol Massimiani Giulia Antonello Paolo Gasco Roberta Bernardini Cristiana Ferrari Lorenzo Ippoliti Gina La Sala Antonio Pietroiusti Ivana Fenoglio Chiara Riganti Luisa Campagnolo |
| author_sort | Valentina Lacconi |
| collection | DOAJ |
| description | Solid lipid nanoparticles (SLNs) have gained interest as drug delivery carriers due to their efficient cellular internalization and increased therapeutic effect of the loaded drug, with minimal side effects. Although recently several studies have shown the possibility to administer SLNs during pregnancy to vehicle mRNA to the placenta, data about the effect of premating exposure to SLNs on pregnancy outcome are scant. Considering that assumption of drug-delivering nanocarriers in reproductive age may potentially affect women’s reproductive health, the aim of the present study was to evaluate whether repeated oral administration of SLNs to female mice prior to mating would influence key pregnancy outcomes. For this purpose, SLNs melatonin loaded (SLN + mlt) or unloaded were orally administered to CD1 female mice at two different dosages—low (7.5 mg/kg) and high (750 mg/kg) —three times a week for 6 weeks. Females mice were mated and pregnancy was monitored from conception to delivery. All the assessed pregnancy parameters, including time to pregnancy, pregnancy duration, litter size, and the presence of any gross anomalies in the pups, and maternal key biochemical parameters were not significantly affected by SLN administration. Embryonic development was also evaluated and no effects on the number of implantation sites, fetus numbers, incidence of fetal resorptions, and measurements of crown-rump length, as well as fetal and placental weights, were observed in the treated mothers. The impact of SLNs on maternal intestinal barrier integrity and inflammation was assessed both in vivo in mice and in vitro using an intestinal epithelial barrier model by qRT-PCR. Results showed that unloaded SLNs, but not the SLN + mlt, affected intestinal barrier integrity. Although variation in the expression of inflammatory cytokines was recorded, this did not reflect in significant histological alterations and the integrity of the intestinal barrier was maintained. The in vitro model further confirmed the biocompatibility of SLNs, showing that both loaded and unloaded SLNs did not affect the integrity of the simulated intestinal epithelial barrier. In conclusion, these data suggest that administering SLNs, as a drug delivery vehicle, prior to conception does not affect either maternal health or fetal development, posing no risk to future pregnancy. |
| format | Article |
| id | doaj-art-989e5e2e1a5e4433aa37f108b5dfde24 |
| institution | Kabale University |
| issn | 2673-3080 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Toxicology |
| spelling | doaj-art-989e5e2e1a5e4433aa37f108b5dfde242025-01-07T05:24:11ZengFrontiers Media S.A.Frontiers in Toxicology2673-30802025-01-01610.3389/ftox.2024.15085981508598Assessing gut barrier integrity and reproductive performance following pre-mating oral administration of solid-lipid-nanoparticles designed for drug deliveryValentina Lacconi0Valentina Lacconi1Micol Massimiani2Micol Massimiani3Giulia Antonello4Paolo Gasco5Roberta Bernardini6Cristiana Ferrari7Lorenzo Ippoliti8Gina La Sala9Antonio Pietroiusti10Ivana Fenoglio11Chiara Riganti12Luisa Campagnolo13Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, ItalyDepartmental Faculty of Medicine, Saint Camillus International University of Health Sciences, Rome, ItalyDepartment of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, ItalyDepartmental Faculty of Medicine, Saint Camillus International University of Health Sciences, Rome, ItalyDepartment of Chemistry, University of Torino, Torino, ItalyNanovector S.r.l., Torino, ItalyDepartment of Translational Medicine and Centro Interdipartimentale di Medicina Comparata, Tecniche Alternative ed Acquacoltura (CIMETA), University of Rome “Tor Vergata”, Rome, ItalyDepartment of Occupational Medicine, University of Rome Tor Vergata, Rome, ItalyDepartmental Faculty of Medicine, Saint Camillus International University of Health Sciences, Rome, ItalyInstitute of Biochemistry and Cell Biology, Italian National Research Council (CNR), Monterotondo Scalo, ItalyDepartmental Faculty of Medicine, Saint Camillus International University of Health Sciences, Rome, ItalyDepartment of Chemistry, University of Torino, Torino, ItalyDepartment of Oncology, University of Torino, Torino, ItalyDepartment of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, ItalySolid lipid nanoparticles (SLNs) have gained interest as drug delivery carriers due to their efficient cellular internalization and increased therapeutic effect of the loaded drug, with minimal side effects. Although recently several studies have shown the possibility to administer SLNs during pregnancy to vehicle mRNA to the placenta, data about the effect of premating exposure to SLNs on pregnancy outcome are scant. Considering that assumption of drug-delivering nanocarriers in reproductive age may potentially affect women’s reproductive health, the aim of the present study was to evaluate whether repeated oral administration of SLNs to female mice prior to mating would influence key pregnancy outcomes. For this purpose, SLNs melatonin loaded (SLN + mlt) or unloaded were orally administered to CD1 female mice at two different dosages—low (7.5 mg/kg) and high (750 mg/kg) —three times a week for 6 weeks. Females mice were mated and pregnancy was monitored from conception to delivery. All the assessed pregnancy parameters, including time to pregnancy, pregnancy duration, litter size, and the presence of any gross anomalies in the pups, and maternal key biochemical parameters were not significantly affected by SLN administration. Embryonic development was also evaluated and no effects on the number of implantation sites, fetus numbers, incidence of fetal resorptions, and measurements of crown-rump length, as well as fetal and placental weights, were observed in the treated mothers. The impact of SLNs on maternal intestinal barrier integrity and inflammation was assessed both in vivo in mice and in vitro using an intestinal epithelial barrier model by qRT-PCR. Results showed that unloaded SLNs, but not the SLN + mlt, affected intestinal barrier integrity. Although variation in the expression of inflammatory cytokines was recorded, this did not reflect in significant histological alterations and the integrity of the intestinal barrier was maintained. The in vitro model further confirmed the biocompatibility of SLNs, showing that both loaded and unloaded SLNs did not affect the integrity of the simulated intestinal epithelial barrier. In conclusion, these data suggest that administering SLNs, as a drug delivery vehicle, prior to conception does not affect either maternal health or fetal development, posing no risk to future pregnancy.https://www.frontiersin.org/articles/10.3389/ftox.2024.1508598/fullsolid-lipid-nanoparticlespregnancygut barrier integrityplacentaembryooral administration |
| spellingShingle | Valentina Lacconi Valentina Lacconi Micol Massimiani Micol Massimiani Giulia Antonello Paolo Gasco Roberta Bernardini Cristiana Ferrari Lorenzo Ippoliti Gina La Sala Antonio Pietroiusti Ivana Fenoglio Chiara Riganti Luisa Campagnolo Assessing gut barrier integrity and reproductive performance following pre-mating oral administration of solid-lipid-nanoparticles designed for drug delivery Frontiers in Toxicology solid-lipid-nanoparticles pregnancy gut barrier integrity placenta embryo oral administration |
| title | Assessing gut barrier integrity and reproductive performance following pre-mating oral administration of solid-lipid-nanoparticles designed for drug delivery |
| title_full | Assessing gut barrier integrity and reproductive performance following pre-mating oral administration of solid-lipid-nanoparticles designed for drug delivery |
| title_fullStr | Assessing gut barrier integrity and reproductive performance following pre-mating oral administration of solid-lipid-nanoparticles designed for drug delivery |
| title_full_unstemmed | Assessing gut barrier integrity and reproductive performance following pre-mating oral administration of solid-lipid-nanoparticles designed for drug delivery |
| title_short | Assessing gut barrier integrity and reproductive performance following pre-mating oral administration of solid-lipid-nanoparticles designed for drug delivery |
| title_sort | assessing gut barrier integrity and reproductive performance following pre mating oral administration of solid lipid nanoparticles designed for drug delivery |
| topic | solid-lipid-nanoparticles pregnancy gut barrier integrity placenta embryo oral administration |
| url | https://www.frontiersin.org/articles/10.3389/ftox.2024.1508598/full |
| work_keys_str_mv | AT valentinalacconi assessinggutbarrierintegrityandreproductiveperformancefollowingprematingoraladministrationofsolidlipidnanoparticlesdesignedfordrugdelivery AT valentinalacconi assessinggutbarrierintegrityandreproductiveperformancefollowingprematingoraladministrationofsolidlipidnanoparticlesdesignedfordrugdelivery AT micolmassimiani assessinggutbarrierintegrityandreproductiveperformancefollowingprematingoraladministrationofsolidlipidnanoparticlesdesignedfordrugdelivery AT micolmassimiani assessinggutbarrierintegrityandreproductiveperformancefollowingprematingoraladministrationofsolidlipidnanoparticlesdesignedfordrugdelivery AT giuliaantonello assessinggutbarrierintegrityandreproductiveperformancefollowingprematingoraladministrationofsolidlipidnanoparticlesdesignedfordrugdelivery AT paologasco assessinggutbarrierintegrityandreproductiveperformancefollowingprematingoraladministrationofsolidlipidnanoparticlesdesignedfordrugdelivery AT robertabernardini assessinggutbarrierintegrityandreproductiveperformancefollowingprematingoraladministrationofsolidlipidnanoparticlesdesignedfordrugdelivery AT cristianaferrari assessinggutbarrierintegrityandreproductiveperformancefollowingprematingoraladministrationofsolidlipidnanoparticlesdesignedfordrugdelivery AT lorenzoippoliti assessinggutbarrierintegrityandreproductiveperformancefollowingprematingoraladministrationofsolidlipidnanoparticlesdesignedfordrugdelivery AT ginalasala assessinggutbarrierintegrityandreproductiveperformancefollowingprematingoraladministrationofsolidlipidnanoparticlesdesignedfordrugdelivery AT antoniopietroiusti assessinggutbarrierintegrityandreproductiveperformancefollowingprematingoraladministrationofsolidlipidnanoparticlesdesignedfordrugdelivery AT ivanafenoglio assessinggutbarrierintegrityandreproductiveperformancefollowingprematingoraladministrationofsolidlipidnanoparticlesdesignedfordrugdelivery AT chiarariganti assessinggutbarrierintegrityandreproductiveperformancefollowingprematingoraladministrationofsolidlipidnanoparticlesdesignedfordrugdelivery AT luisacampagnolo assessinggutbarrierintegrityandreproductiveperformancefollowingprematingoraladministrationofsolidlipidnanoparticlesdesignedfordrugdelivery |