Exosomal delivery of IL-10: Biodistribution, pharmacokinetics, and preterm birth prevention strategies

Abstract

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.