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Acid-resistant chemotactic DNA micromotors for probiotic delivery in inflammatory bowel disease
Zinan Zhao1, Yao Xu1, Yong Hu2
1Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai, 201804, P. R. China.
Abstract:
Microcapsules composed of synthetic polymeric matrices have attracted considerable attention in delivering oral probiotics. However, existing polymeric microcapsules demonstrate inadequate acid resistance and adaptability, as well as deficiency in the inflamed colon-specificity and uncontrolled release of probiotics therein. Herein, a DNA microcapsule is prepared as a probiotic-transporting micromotor through photo-crosslinking of hyaluronic acid methacrylate and acrydite-modified A-/C-rich oligomers within the microfludically generated droplets in the presence of nitric oxide-cleavable crosslinker and gas donor manganese carbonyl (MnCO). As the microcapsules traverse stomach, duodenum, and ultimately colon, the formation and dissociation of A-motif and i-motif structures instigate a reversible shrinking-swelling transition of microcapsules to preserve probiotic viability. Subsequently, the microcapsules exhibit chemotaxis towards inflamed colon site, driven by a gas-generating reaction between MnCO and elevated reactive oxygen species. Following disintegration of the microcapsules, triggered by endogenous nitric oxide, probiotics are released to reshape the dysbiosis of intestinal microflora. This advanced delivery system offers significant promise for the effective clinical management of inflammatory bowel disease.
Insights
New DNA microcapsules offer improved oral probiotic delivery for inflammatory bowel disease (IBD). These micromotors protect probiotics and target the inflamed colon, enhancing therapeutic potential.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Gastroenterology
Background:
- Synthetic polymeric microcapsules are used for oral probiotic delivery but lack acid resistance, colon specificity, and controlled release.
- Existing systems fail to adequately protect probiotics in the harsh gastrointestinal environment and target inflamed colonic sites.
Purpose of the Study:
- To develop advanced DNA microcapsules as micromotors for enhanced oral probiotic delivery.
- To improve probiotic viability, achieve inflamed colon-specificity, and enable controlled release for inflammatory bowel disease (IBD) management.
Main Methods:
- Fabrication of DNA microcapsules via photo-crosslinking of hyaluronic acid methacrylate and A-/C-rich oligomers.
- Incorporation of nitric oxide-cleavable crosslinkers and manganese carbonyl (MnCO) as a gas donor.
- Utilizing reversible A-motif and i-motif structural transitions for shrinking-swelling behavior and chemotaxis towards reactive oxygen species (ROS) in inflamed colons.
Main Results:
- The DNA microcapsules demonstrated a reversible shrinking-swelling transition, preserving probiotic viability throughout gastrointestinal transit.
- The microcapsules exhibited chemotaxis towards inflamed colon sites, driven by MnCO reaction with elevated ROS.
- Nitric oxide triggered microcapsule disintegration, facilitating controlled probiotic release.
Conclusions:
- The developed DNA microcapsule system shows significant promise as an advanced delivery vehicle for oral probiotics.
- This technology offers a potential strategy for reshaping intestinal microflora and managing inflammatory bowel disease (IBD).
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