Single-dose oral administration of drug-loaded magnetic 3D-printed microbullets for eradication of Helicobacter pylori

Abstract

Infections of Helicobacter pylori (H. pylori) affect 42.1% of Chinese and 43.1% of the world population. H. pylori inhabits the mucous sublayer at the pylorus, leading to gastric ulcers, gastritis, and even cancer. Oral antibiotics are usually used to treat H. pylori infections, whereas traditional quadruple therapy has side effects including headaches, nausea, diarrhea, intestinal dysbacteriosis, antibiotic resistance, and repeat infections. Here, a drug-loaded magnetic microbullet was designed to realize long-term retention in the stomach for one-shot treatment for H. pylori infections. It comprises a hollow cylinder wherein eight microneedles homogenously distribute at the top and several round pores located at the bottom. It was three-dimensional (3D)-printed by stereolithography. A clarithromycin (CAM) ground mixture (CGM) was prepared to improve solubility. Enough CGM powders were filled into the cylinder, covered by a small round magnet, and sealed to form a CAM-loaded magnetic microbullet (CMMB). CAM continually released from CMMBs for >24 h. With outside magnetic guidance, an oral CMMB targeted the pylorus site and the microneedles immediately headed into the mucosa followed by long-term local drug release. The in vitro and in vivo safety of CMMBs was confirmed, where their swelling rates were low, and the oral CMMB was finally completely evacuated. An oral CMMB was administered to H. pylori-infected mice and maintained in the stomach for 36 h with magnetic guidance, and the successful eradication of H. pylori was confirmed after single-dose administration. Oral CMMBs are a convenient medication for the eradication of H. pylori.

Keywords

3D printing / Helicobacter pylori / Magnetic guidance / Clarithromycin / Drug delivery system / Microbullet

Conflicts of interest

The authors declare that they have no conflict of interest.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (82073791).

Supplementary materials

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.ajps.2024.101013. The figures and tables with "S" before the serial number are included in the Supplementary material.

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