A Double-Layer Polysaccharide Hydrogel (DPH) for the Enhanced Intestine-Targeted Oral Delivery of Probiotics
Wen-Can Huang,
Wenjie Wang,
Wei Wang,
Yanan Hao,
Changhu Xue,
Xiangzhao Mao
Affiliations
Wen-Can Huang
State Key Laboratory of Marine Food Processing and Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266404, China.; Qingdao Key Laboratory of Food Biotechnology, Qingdao 266404, China; Key Laboratory of Biological Processing of Aquatic Products, China National Light Industry, Qingdao 266404, China
Wenjie Wang
State Key Laboratory of Marine Food Processing and Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266404, China.; Qingdao Key Laboratory of Food Biotechnology, Qingdao 266404, China; Key Laboratory of Biological Processing of Aquatic Products, China National Light Industry, Qingdao 266404, China
Wei Wang
State Key Laboratory of Marine Food Processing and Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266404, China.; Qingdao Key Laboratory of Food Biotechnology, Qingdao 266404, China; Key Laboratory of Biological Processing of Aquatic Products, China National Light Industry, Qingdao 266404, China
Yanan Hao
State Key Laboratory of Marine Food Processing and Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266404, China.; Qingdao Key Laboratory of Food Biotechnology, Qingdao 266404, China; Key Laboratory of Biological Processing of Aquatic Products, China National Light Industry, Qingdao 266404, China
Changhu Xue
State Key Laboratory of Marine Food Processing and Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266404, China.; Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China; Corresponding authors.
Xiangzhao Mao
State Key Laboratory of Marine Food Processing and Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266404, China.; Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China; Qingdao Key Laboratory of Food Biotechnology, Qingdao 266404, China; Key Laboratory of Biological Processing of Aquatic Products, China National Light Industry, Qingdao 266404, China; Corresponding authors.
Transplantation of probiotics to the intestine can positively regulate the gut microbiota, thereby promoting the immune system and treating various diseases. However, the harsh gastrointestinal environment and short retention time in the gastrointestinal tract significantly limit the bioavailability and intestinal colonization of probiotics. Herein, we present a double-layer polysaccharide hydrogel (DPH) in the form of a double-layer structure composed of a carboxymethyl cellulose (CMCL) supramolecular inner layer and a dialdehyde alginate (DAA) cross-linked carboxymethyl chitosan (CMCS) outer layer. This double-layer structure allows DPH to encapsulate and deliver probiotics in a targeted manner within the body. In the stomach, the cage structure of the DPH is closed, and the outer layer absorbs surrounding liquids to form a barrier to protect the probiotics from gastric fluids. In the intestine, the cage structure opens and disintegrates, releasing the probiotics. Thus, DPH endows probiotics with excellent intestine-targeted delivery, improved oral bioavailability, enhanced gastrointestinal tract tolerance, and robust mucoadhesion capacity. The encapsulated probiotics exhibit almost unchanged bioactivity in the gastrointestinal tract before release, as well as improved oral delivery. In particular, probiotics encapsulated by DPH exhibit 100.1 times higher bioavailability and 10.6 times higher mucoadhesion than free probiotics in an animal model 48 h post-treatment. In addition, with a remarkable ability to survive and be retained in the intestine, probiotics encapsulated by DPH show excellent in vitro and in vivo competition with pathogens. Notably, DAA-mediated dynamic crosslinking not only maintains the overall integrity of the hydrogels but also controls the release timing of the probiotics. Thus, it is expected that encapsulated substances (probiotics, proteins, etc.) can be delivered to specific sites of the intestinal tract by means of DPH, by controlling the dynamic covalent crosslinking.
