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Steinman, D.

Publications and source records attributed to Steinman, D..

2 recordsLinked to original sources
bioRxiv2025

Bacterial extracellular vesicles as a tunable platform for vaginal drug delivery

There is a critical gap in the development of new therapeutic platforms designed to treat gynecologic and obstetric diseases. Compared to systemic drug delivery, vaginal drug administration of nanoparticle formulations limits off-target side effects while increasing therapeutic concentration in target tissues, showing promise for clinical translation. However, these formulations suffer from limited scalability, high-cost reagents, and long optimization timelines. Recent work highlights the potential of bacterial extracellular vesicles (bEVs) as a low-cost, tunable platform for therapeutic applications. Here, we evaluate bEVs as a therapeutic carrier for vaginal drug delivery. We demonstrate the loading of the model protein moxNeonGreen into Escherichia coli Nissle 1917 bEVs. By optimizing growth parameters, we increase protein loading into bEVs. We evaluate the effect of bEVs on the vaginal microenvironment, and observe no negative impact on vaginal epithelial cells, endocervical cells, or vaginal bacteria in vitro. Additionally, we observe the retention of bEVs in the murine female reproductive tract for more than six hours. This study provides a framework for using genetically engineered bEVs to rapidly generate customizable therapies for a range of gynecologic and obstetric conditions, addressing longstanding challenges in womens health therapeutics. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=50 SRC="FIGDIR/small/658669v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@e483d2org.highwire.dtl.DTLVardef@8a6d2corg.highwire.dtl.DTLVardef@5756borg.highwire.dtl.DTLVardef@5fdb67_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗
bioRxiv2025

Vaginal bacteria-derived extracellular vesicles diffuse through human cervicovaginal mucus to enable bacterial signaling to upper female reproductive tract tissues

The composition of the vaginal microenvironment has significant implications for gynecologic and obstetric outcomes. Where a Lactobacillus-dominated microenvironment is typically considered optimal, a polymicrobial environment is associated with increased risk for female reproductive diseases. Recent work has examined bacteria-derived extracellular vesicles (bEVs) as an important mode of microbe-host communication in the female reproductive tract, with bEVs exhibiting unique species- and strain-level functions that may influence womens health outcomes. However, in order to communicate with female reproductive tissues, bEVs must be able to penetrate the protective cervicovaginal mucus barrier. As the first line of defense against bacteria and pathogens, cervicovaginal mucus protects against infection in the female reproductive tract through steric, hydrophobic, and electrostatic interactions with foreign pathogens. Here, we hypothesize that the physical properties of bacteria-derived extracellular vesicles enable their mobility through cervicovaginal mucus and permit interactions with upper female reproductive tract tissues. We demonstrate that the barrier properties of mucus allow increased diffusion of bEVs, compared to whole bacteria. We evaluate the uptake of bEVs by, and the resulting effects on, human vaginal epithelial, endometrial, and placental cells, highlighting potential mechanisms of action by which vaginal dysbiosis contributes to gynecologic and obstetric diseases. Our work demonstrates the ability of bEVs to mediate female reproductive diseases and highlights their potential as therapeutic modalities for treating dysbiosis and dysbiosis-associated diseases in the female reproductive tract.

bioengineering↗