Bacteria-Induced Colloidal Encapsulation for Probiotic Oral Delivery

Abstract

Probiotic oral delivery has crucial implications in biomedical engineering, but its oral bioavailability remains unsatisfactory because of the limited survival and colonization of probiotics in the harsh gastrointestinal tract. Here, a bacteria-induced encapsulation strategy is achieved by assembling metastable colloids to enhance the oral bioavailability of probiotics. The colloids (NTc) composed of amino-modified poly-β-cyclodextrin and tannic acid are formed based on the balance of host−guest interaction-driven attraction and electrostatic repulsion between colloids. Negatively charged probiotics electrostatically attract positively charged NTc to break the balance and induce further assembly surrounding the probiotics. Through a facile one-step mixing, 97% of bacteria are rapidly encapsulated into NTc shells within 10 s, with a high utilization rate of feeding colloids of 91%. More importantly, we show that the compact, thick, and positively charged NTc shells synergistically endow the encapsulated probiotics with strong resistance against simulated gastric fluid with an excellent survival rate of up to 19%, 7500 times superior to the commercial enteric material L100. Moreover, owing to the dynamically noncovalent and selfadaptive nature of host−guest interactions, NTc shells support the proliferation of the encapsulated EcN comparable with that of the naked EcN. In vitro and in vivo experiments also confirm that the NTc-encapsulated probiotics possess durable intestinal adhesion, continuous proliferation activity, enhanced oral bioavailability, good oral biosafety, and excellent therapeutic efficacy in a colitis mouse model. This facile bacteria-induced colloidal encapsulation strategy may extend to various microbes as oral bioagents for treating various diseases.

Biomaterials and Encapsulation Techniques for Probiotics: Current Status and Future Prospects in Biomedical Applications

“…Jia Lingyun et al used positively charged colloids (NTc) composed of amino-modified poly-β-cyclodextrin and tannic acid to encapsulate negatively charged probiotics, showing strong resistance to simulated gastric acid with a survival rate of up to 19%, which is 7500 times higher than that of the commercial enteric material L100. The encapsulated probiotics showed good therapeutic effects in a colitis mouse model [184]. Chen Qian et al utilized electrostatic self-assembly to encapsulate E. coli strains expressing catalase and superoxide dismutase with chitosan and sodium alginate as effective biofilms.…”

“…This is 7500 times higher than commercial entericcoated material L100. The oral availability of encapsulated probiotics increased by about five times compared to non-encapsulated probiotics [184].…”

Bacteria‐Based Living Probes: Preparation and the Applications in Bioimaging and Diagnosis

“…Han et al reported a SYTO-9-labeled bacteriabased probe that could be electrostatically encased in a colloidal shell composed of amino-modified poly-𝛽-cyclodextrin and tannic acid, which enhanced oral availability and prolonged the intestinal adhesion duration, showing by in vivo imaging. [164] Liu et al encapsulated GFP-expressing bacteria with a lipid membrane coating through interfacial supramolecular self-assembly [161] Copyright 2019, American Chemical Society. b) 18 F-FDS-assisted PET imaging of E. coli MG1655 in tumor-bearing mice.…”

“…reported a SYTO‐9‐labeled bacteria‐based probe that could be electrostatically encased in a colloidal shell composed of amino‐modified poly‐β‐cyclodextrin and tannic acid, which enhanced oral availability and prolonged the intestinal adhesion duration, showing by in vivo imaging. [ 164 ] Liu et al encapsulated GFP‐expressing bacteria with a lipid membrane coating through interfacial supramolecular self‐assembly to build a bacteria‐based probe, with abilities to fight against various harsh environments, such as gastric acid and antibiotics, as well as to visualize the colonization of bacteria in the intestinal tract in vivo via fluorescent imaging. [ 40 ] H. pylori is a bacterium with high adaptability in extreme environments and can cause different diseases, such as peptic ulcers, gastric ulcers, and gastric cancer.…”

Preparation of Polysaccharide–Protein Hydrogels with an Ultrafast Self-Healing Property as a Superior Oral Delivery System of Probiotics

“…Ultimately, probiotics show very limited bioavailability, and they can hardly function properly in the intestine. Therefore, it is of great significance for researchers to establish new probiotic delivery strategies that can improve the oral probiotics’ bioavailability and intestinal colonization rate. , …”