Abstract
The oral delivery of macromolecules is quite challenging due to environmental insults and biological barriers encountered along the gastrointestinal (GI) tract. Benefiting from their living characteristics, diverse bacterial species have been engineered as intelligent platforms to deliver various therapeutics. To tackle difficulties in oral delivery, innovative bacteria-based microdevices have been developed by virtue of advancements in synthetic biology and nanotechnology, with aims to overcome the instability and short half-life of macromolecules in the GI tract. In this review, we summarize the main classes of macromolecules that are produced and delivered through the oral ingestion of bacteria and bacterial derivatives. Furtherly, we discuss the engineering strategies and biomedical applications of these living microdevices in disease diagnosis, bioimaging, and treatment. Finally, we highlight the advantages as well as the limitations of these engineered bacteria used as platforms for the oral delivery of macromolecules and also propose their potential for clinical translation. The results summarized in this review article would contribute to the invention of next-generation bacteria-based systems for the oral delivery of macromolecules.
Highlights
Biologics, known as biomacromolecular pharmaceuticals, including peptides, proteins, antibodies, polysaccharides, and nucleic acids, produced from various biological systems, such as microorganisms, mammalian cells, and animal- or human-derived tissues via biotechnological means [1]
Biologicals provide high specificity and activity thanks to their large and complex structures, there are problems and obstacles that need to be solved for the use of these drugs as most of them suffer from low stability, short half-life, and limited penetration across biological barriers [2,8]
Despite a remarkable progress has been made in this field, the oral delivery of therapeutic biomacromolecular drugs by bacteria-based microdevices faces a couple of substantial obstacles that are needed to be overcome urgently
Summary
Known as biomacromolecular pharmaceuticals, including peptides, proteins, antibodies, polysaccharides, and nucleic acids, produced from various biological systems, such as microorganisms, mammalian cells, and animal- or human-derived tissues via biotechnological means [1]. Compared to conventional drug livery systems for the oral delivery of macromolecules, bacterial microdevices exhibit the delivery systems for the oral delivery of macromolecules, bacterial microdevices exhibit advantages of the in situ production of biologicals, long-term colonization in the intesthe advantages of the in situ production of biologicals, long-term colonization in the intine, targeting ability, and review, we we testine, targeting ability, andversatility versatilitytotoload loaddiverse diversedrugs drugs [24,25] In this this review, mainly focus focus on on bacteria-based bacteria-based microdevices microdevices and and summarize summarize their their current current progress progress and and mainly future prospects prospectsfor forthe theoral oraldelivery delivery biomacromolecules
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