Feasibility of engineered Bacillus subtilis for use as a microbiome-based topical drug delivery platform.
Bioeng Transl Med
; 9(4): e10645, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-39036074
ABSTRACT
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.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Bioeng Transl Med
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Estados Unidos