Montgomery Veronica A, Wood-Yang Amy J, Styczynski Mark P, Prausnitz Mark R
Wallace H. Coulter Department of Biomedical Engineering at Emory University and Georgia Tech Georgia Institute of Technology Atlanta Georgia USA.
School of Chemical and Biomolecular Engineering Georgia Institute of Technology Atlanta Georgia USA.
Bioeng Transl Med. 2024 Jan 2;9(4):e10645. doi: 10.1002/btm2.10645. eCollection 2024 Jul.
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 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 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 . 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 for topical drug delivery.
不遵医嘱用药是医疗保健中的一项重大挑战，会导致患者的治疗效果恶化。减少所需给药频率可提高依从性，但对于局部给药来说具有挑战性，因为局部制剂在皮肤上的停留时间通常较短。在本研究中，我们试图确定开发一种基于微生物群的长效局部给药平台用于在皮肤上生产和递送药物的可行性，该平台以绿色荧光蛋白作为用于递送的模型异源蛋白进行评估。我们建立了皮肤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。使用猪皮模型和人皮肤组织培养模型，我们观察到递送的细菌持续存在数天，并且几乎没有证据表明对人角质形成细胞具有细胞毒性。最后，使用体内小鼠模型，我们发现每隔一天给药时，递送的细菌在皮肤上持续存在至少1天，并且似乎不存在安全问题。综上所述，我们的结果支持使用工程化细菌进行局部给药的可行性。
