Forough Parhizkar, Mehdi Yousefi, Mohammad Sadegh Soltani-Zangbar, Zahra Parhizkar, Leili Aghebati-Maleki, Soheil Abbaspour-Ravasjani, Roza Motavalli, Amin Alizadegan, Maryam Mojahedi, Sina Baharaghdam, Amin Kamrani, Shahla Danaii, Mehdi Talebi, Farhad Jadidi-Niaragh, Hamed Hamishehkar, Hossein Samadi Kafil, Ata Mahmoodpoor, Javad Ahmadian Heris
{"title":"含有西罗莫司和环孢素的纳米结构脂质载体:开发、表征和体外评估复发性妊娠失败患者的 T 细胞特征。","authors":"Forough Parhizkar, Mehdi Yousefi, Mohammad Sadegh Soltani-Zangbar, Zahra Parhizkar, Leili Aghebati-Maleki, Soheil Abbaspour-Ravasjani, Roza Motavalli, Amin Alizadegan, Maryam Mojahedi, Sina Baharaghdam, Amin Kamrani, Shahla Danaii, Mehdi Talebi, Farhad Jadidi-Niaragh, Hamed Hamishehkar, Hossein Samadi Kafil, Ata Mahmoodpoor, Javad Ahmadian Heris","doi":"10.1002/rmb2.12509","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>The authors developed nanostructured lipid carriers (NLCs) loaded with sirolimus (SRL) and cyclosporine (CsA) to improve their therapeutic efficacy in recurrent pregnancy loss (RPL) patients.</p><p><strong>Methods: </strong>Mono-delivery and co-delivery of SRL and CsA by NLCs (S-NLCs, C-NLCs, and S-C-NLCs) were developed. The MTT assay was used to study the optimum dose of formulations. PCR, Western blotting, and ELISA were also conducted.</p><p><strong>Results: </strong>Well-designed nanodrugs with a suitable size, zeta potential, desirable encapsulation efficiency drug loading, and cellular uptake confirmed optimum formulations. Based on cell viability, the amounts of SRL and CsA could be reduced greatly due to the co-delivery by NLCs. Following S-NLCs and C-NLCs interventions in T cells of patients with RPL and immune abnormality, a significant difference was observed in transcription factors and cytokine levels of Th1, Th17, and Tregs compared with healthy samples. Thus, a higher level of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-17, and IL-21) and their regulators (T-bet and RORγt), as well as a lower level of an anti-inflammatory cytokine (IL-10) and its regulatory (Foxp3), were observed. However, no significant difference was found following the S-C-NLCs intervention.</p><p><strong>Conclusions: </strong>S-C-NLCs effectively balance the immune responses in peripheral T cells in RPL patients to induce maternal immune tolerance.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2023-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/55/c5/RMB2-22-e12509.PMC10026110.pdf","citationCount":"0","resultStr":"{\"title\":\"Sirolimus- and cyclosporine-loaded nanostructured lipid carriers: Development, characterization, and in vitro evaluation in T-cell profiles of patients with a history of recurrent pregnancy loss.\",\"authors\":\"Forough Parhizkar, Mehdi Yousefi, Mohammad Sadegh Soltani-Zangbar, Zahra Parhizkar, Leili Aghebati-Maleki, Soheil Abbaspour-Ravasjani, Roza Motavalli, Amin Alizadegan, Maryam Mojahedi, Sina Baharaghdam, Amin Kamrani, Shahla Danaii, Mehdi Talebi, Farhad Jadidi-Niaragh, Hamed Hamishehkar, Hossein Samadi Kafil, Ata Mahmoodpoor, Javad Ahmadian Heris\",\"doi\":\"10.1002/rmb2.12509\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>The authors developed nanostructured lipid carriers (NLCs) loaded with sirolimus (SRL) and cyclosporine (CsA) to improve their therapeutic efficacy in recurrent pregnancy loss (RPL) patients.</p><p><strong>Methods: </strong>Mono-delivery and co-delivery of SRL and CsA by NLCs (S-NLCs, C-NLCs, and S-C-NLCs) were developed. The MTT assay was used to study the optimum dose of formulations. PCR, Western blotting, and ELISA were also conducted.</p><p><strong>Results: </strong>Well-designed nanodrugs with a suitable size, zeta potential, desirable encapsulation efficiency drug loading, and cellular uptake confirmed optimum formulations. Based on cell viability, the amounts of SRL and CsA could be reduced greatly due to the co-delivery by NLCs. Following S-NLCs and C-NLCs interventions in T cells of patients with RPL and immune abnormality, a significant difference was observed in transcription factors and cytokine levels of Th1, Th17, and Tregs compared with healthy samples. Thus, a higher level of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-17, and IL-21) and their regulators (T-bet and RORγt), as well as a lower level of an anti-inflammatory cytokine (IL-10) and its regulatory (Foxp3), were observed. However, no significant difference was found following the S-C-NLCs intervention.</p><p><strong>Conclusions: </strong>S-C-NLCs effectively balance the immune responses in peripheral T cells in RPL patients to induce maternal immune tolerance.</p>\",\"PeriodicalId\":21116,\"journal\":{\"name\":\"Reproductive Medicine and Biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2023-03-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/55/c5/RMB2-22-e12509.PMC10026110.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Reproductive Medicine and Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/rmb2.12509\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"OBSTETRICS & GYNECOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive Medicine and Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/rmb2.12509","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
Sirolimus- and cyclosporine-loaded nanostructured lipid carriers: Development, characterization, and in vitro evaluation in T-cell profiles of patients with a history of recurrent pregnancy loss.
Purpose: The authors developed nanostructured lipid carriers (NLCs) loaded with sirolimus (SRL) and cyclosporine (CsA) to improve their therapeutic efficacy in recurrent pregnancy loss (RPL) patients.
Methods: Mono-delivery and co-delivery of SRL and CsA by NLCs (S-NLCs, C-NLCs, and S-C-NLCs) were developed. The MTT assay was used to study the optimum dose of formulations. PCR, Western blotting, and ELISA were also conducted.
Results: Well-designed nanodrugs with a suitable size, zeta potential, desirable encapsulation efficiency drug loading, and cellular uptake confirmed optimum formulations. Based on cell viability, the amounts of SRL and CsA could be reduced greatly due to the co-delivery by NLCs. Following S-NLCs and C-NLCs interventions in T cells of patients with RPL and immune abnormality, a significant difference was observed in transcription factors and cytokine levels of Th1, Th17, and Tregs compared with healthy samples. Thus, a higher level of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-17, and IL-21) and their regulators (T-bet and RORγt), as well as a lower level of an anti-inflammatory cytokine (IL-10) and its regulatory (Foxp3), were observed. However, no significant difference was found following the S-C-NLCs intervention.
Conclusions: S-C-NLCs effectively balance the immune responses in peripheral T cells in RPL patients to induce maternal immune tolerance.
期刊介绍:
Reproductive Medicine and Biology (RMB) is the official English journal of the Japan Society for Reproductive Medicine, the Japan Society of Fertilization and Implantation, the Japan Society of Andrology, and publishes original research articles that report new findings or concepts in all aspects of reproductive phenomena in all kinds of mammals. Papers in any of the following fields will be considered: andrology, endocrinology, oncology, immunology, genetics, function of gonads and genital tracts, erectile dysfunction, gametogenesis, function of accessory sex organs, fertilization, embryogenesis, embryo manipulation, pregnancy, implantation, ontogenesis, infectious disease, contraception, etc.