4.8 Article

Hydrogel microcapsules containing engineered bacteria for sustained production and release of protein drugs

Journal

BIOMATERIALS
Volume 287, Issue -, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2022.121619

Keywords

Synthetic biology; Hydrogel microcapsules; Sustained release; Bacterial microcomponents; Optogenetics

Funding

  1. National Key Research and Development Program of China [2019YFA0906500]
  2. National Natural Science Foundation of China [32122047, 31971300]
  3. Key> Research and Development Program of Tianjin [19YFZCSY00190]

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Engineered bacterial microcapsules show potential for durable release of protein drugs, with applications in treating diabetes and preventing tumor growth.
Subcutaneous administration of sustained-release formulations is a common strategy for protein drugs, which avoids first pass effect and has high bioavailability. However, conventional sustained-release strategies can only load a limited amount of drug, leading to insufficient durability. Herein, we developed microcapsules based on engineered bacteria for sustained release of protein drugs. Engineered bacteria were carried in microcapsules for subcutaneous administration, with a production-lysis circuit for sustained protein production and release. Administrated in diabetic rats, engineered bacteria microcapsules was observed to smoothly release Exendin-4 for 2 weeks and reduce blood glucose. In another example, by releasing subunit vaccines with bacterial microcomponents as vehicles, engineered bacterial microcapsules activated specific immunity in mice and achieved tumor prevention. The engineered bacteria microcapsules have potential to durably release protein drugs and show versatility on the size of drugs. It might be a promising design strategy for long-acting in situ drug

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