Infection with Helicobacter pylori (Hp) is one of the leading causes of stomach cancer. The ability to treat Hp infection is hampered by a lack of stomach gastric acid environment. This work introduces a nanoliposome that can rapidly adjust the gastric acid environment to ensure a drug’s optimal efficacy. We introduce CaCO3@Fe–TP@EggPC nanoliposomes (CTE NLs) that are composed of Fe3+ and tea polyphenols (TPs) forming complexes on the surface of internal CaCO3 and then with lecithin producing a phospholipid bilayer on the polyphenols’ outer surface. Through the action of iron–TP chelate, the phospholipid layer can fuse with the bacterial membrane to eliminate Hp. Furthermore, CaCO3 can promptly consume the excessive gastric acid, ensuring an ideal operating environment for the chelate. TPs, on the other hand, can improve the inflammation and gut microbes in the body. The experimental results show that CTE NLs can quickly consume protons in the stomach and reduce the bacterial burden by 1.2 orders of magnitude while reducing the inflammatory factors in the body. The biosafety evaluation revealed that nanoliposomes have good biocompatibility and provide a new strategy for treating Hp infection.
Destruction of insulin caused by the gastric microenvironment and rapid deactivation pose inevitable barriers to oral macromolecular absorption, especially for most peptide and protein drugs. In this study, we developed high-density sodium alginate microspheres composed of magnesium oxide and urease to address these challenges. These microspheres aim to anchor the gastric mucus layer and induce microenvironmental liquefaction, thereby enhancing gastric retention and the protection of insulin. The sedimentation test confirmed the capability of the Ins/Ur/MgO@SA microsphere to rapidly traverse the gastric juice under the influence of gravity. Additionally, the urease immobilized on the Ins/Ur/MgO@SA microspheres catalyzes the hydrolysis of urea in the gastric mucus and promotes the liquefaction of mucus, which is beneficial for microsphere retention. The inclusion of MgO particles and urease, acting as pHM modifiers, helps in adjusting the local pH to avoid gastric acid-induced damage. Subsequently, an in vivo pharmacokinetic experiment verified that the relative bioavailability of the p.o. Ins/Ur/MgO@SA treated group was 15-fold higher than that of the p.o.insulin treated group. Meanwhile, satisfactory blood glucose level (BGL) reduction was observed in diabetic animals. In conclusion, Ins/Ur/MgO@SA microspheres demonstrate high biocompatibility as insulin carriers with prolonged drug release time and increased gastric retention properties, showing a far-reaching strategy for oral macromolecular drug delivery.
Xiaonan Chen,Yiqing Zou,Shuqi Zhang,Pengchao Fang,Shuxuan Li,Pengyu Li,Yingying Sun,Gang Yuan,Haiyan Hu
Helicobacter pylori ( H. pylori ), creating a global infection rate over 50%, presents great challenges in clinical therapies due to its complex pathological microenvironment in vivo . To improve the eradication efficacy, herein we fabricated a pharmaceutical vesicle RHL/Cl-Ch-cal where cholesterol-PEG, calcitriol and first-line antibiotic clarithromycin were co-loaded in the rhamnolipid-composed outer lipid layer. RHL/Cl-Ch-cal could quickly penetrate through gastric mucus layer to reach H. pylori infection sites, and then effectively destroyed the architecture of H. pylori biofilms, killed dispersed H. pylori and inhibited the re-adhesion of residual bacteria (called biofilms eradication tetralogy). Moreover, RHL/Cl-Ch-cal activated the host immune response to H. pylori by replenishing cholesterol to repair lipid raft on the cell membrane of host epithelial cells. Finally, RHL/Cl-Ch-cal killed the intracellular H. pylori through recovering the lysosomal acidification and assisting degradation. In experiments, RHL/Cl-Ch-cal demonstrated prominent anti- H. pylori efficacy in the classical H. pylori -infected mice model. Therefore, the study provides a “comprehensive attack” strategy for anti- H. pylori therapies including biofilms eradication tetralogy, immune activation and intracellular bacteria killing.
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