将工程枯草芽孢杆菌用作微生物局部给药平台的可行性

IF 6.1 2区 医学 Q1 ENGINEERING, BIOMEDICAL Bioengineering & Translational Medicine Pub Date : 2024-01-02 DOI:10.1002/btm2.10645
Veronica A. Montgomery, Amy J. Wood-Yang, Mark P. Styczynski, Mark R. Prausnitz
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引用次数: 0

摘要

不坚持用药是医疗保健领域的一大挑战,会导致患者的治疗效果恶化。减少用药次数可以提高用药依从性,但由于外用制剂在皮肤上的停留时间通常较短,因此对于外用给药来说具有挑战性。在本研究中,我们试图确定利用枯草芽孢杆菌开发一种基于微生物组的长效局部给药平台的可行性,以绿色荧光蛋白作为给药的异源蛋白模型。我们开发了皮肤上细菌种群动态的计算模型,并利用其定性预测来指导实验设计选择。通过使用猪体外皮肤模型和人体皮肤组织培养模型,我们发现递送的细菌可持续存在多天,并且在体外几乎没有观察到对人体角质细胞产生细胞毒性的证据。最后,通过使用体内小鼠模型,我们发现在隔天一次的施用过程中,递送的细菌在皮肤上至少能持续存在 1 天,似乎不存在安全问题。综上所述,我们的研究结果支持使用工程化枯草杆菌进行局部给药的可行性。
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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 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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来源期刊
Bioengineering & Translational Medicine
Bioengineering & Translational Medicine Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
8.40
自引率
4.10%
发文量
150
审稿时长
12 weeks
期刊介绍: Bioengineering & Translational Medicine, an official, peer-reviewed online open-access journal of the American Institute of Chemical Engineers (AIChE) and the Society for Biological Engineering (SBE), focuses on how chemical and biological engineering approaches drive innovative technologies and solutions that impact clinical practice and commercial healthcare products.
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