Feasibility of engineered Bacillus subtilis for use as a microbiome‐based topical drug delivery platform

Non‐adherence to medication is a major challenge in healthcare that results in worsened treatment outcomes for patients. Reducing the frequency of required administrations could improve adherence but is challenging for topical drug delivery due to the generally short residence time of topical formul...

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Bibliographic Details
Published in:Bioengineering & translational medicine 2024-07, Vol.9 (4), p.e10645-n/a
Main Authors: Montgomery, Veronica A., Wood‐Yang, Amy J., Styczynski, Mark P., Prausnitz, Mark R.
Format: Article
Language:English
Subjects:
Acne
Antibiotics
Bacillus subtilis
Bacteria
Biocompatibility
Cell growth
Dermatology
Design of experiments
E coli
engineered live biotherapeutics
Experiments
Feasibility studies
Fluorescence
Genetic engineering
In vivo methods and tests
Pigskins
Plasmids
Proteins
Side effects
Simulation
Skin
skin microbiome
topical drug delivery
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Summary:Non‐adherence to medication is a major challenge in healthcare that results in worsened treatment outcomes for patients. Reducing the frequency of required administrations could improve adherence but is challenging for topical drug delivery due to the generally short residence time of topical formulations on the skin. In this study, we sought to determine the feasibility of developing a microbiome‐based, long‐acting, topical delivery platform using Bacillus subtilis for drug production and delivery on the skin, which was assessed using green fluorescent protein as a model heterologous protein for delivery. We developed a computational model of bacteria population dynamics on the skin and used its qualitative predictions to guide experimental design choices. Using an ex vivo pig skin model and a human skin tissue culture model, we saw persistence of delivered bacteria for multiple days and observed little evidence of cytotoxicity to human keratinocyte cells in vitro. Finally, using an in vivo mouse model, we found that the delivered bacteria persisted on the skin for at least 1 day during every‐other‐day application and did not appear to present safety concerns. Taken together, our results support the feasibility of using engineered B. subtilis for topical drug delivery.
ISSN:2380-6761
2380-6761
DOI:10.1002/btm2.10645