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.

The Impact of New Immunological Therapeutic Strategies on Recurrent Miscarriage and Recurrent Implantation Failure.

Maternal-fetal immune dysregulation is one of the risk factors that increases the probability of embryo rejection and reproductive failure. The stimulation of immunological tolerance and suppression of immunological rejection are prerequisites for protecting embryos and preventing immunological attacks. Hence, it appears that immunomodulatory and immunosuppressive therapies can manage reproductive failures by controlling immune cells. The current medical literature has shown that immunotherapy approaches and cell therapy have promising results in improving pregnancy outcomes and live birth rates. These outcomes are obtained by regulating maternal immune responses, and exerting positive effects on human reproductive processes.