Development and Evaluation of Novel Amoxicillin and Phytic Acid-Loaded Gastro-Retentive Mucoadhesive Pectin Microparticles for the Management of Helicobacter pylori Infections

Amoxicillin, a treatment option widely employed against H. pylori infection, is becoming ineffective due to the rising antimicrobial resistance. The poor stability of amoxicillin in gastric juice, as well as amoxicillin resistance in H. pylori, has a negative impact on amoxicillin’s therapeutic efficacy. Because of its metal chelating capacity, phytic acid has been shown to improve the antibacterial effectiveness of adjunct antimicrobials. Gastroretentive drug delivery carriers present a viable approach for treating gastric conditions owing to their higher gastric residence time and controlled drug release properties.

In the current investigation, amoxicillin and phytic acid loaded benzalkonium chloride (BAC) cross-linked pectin microparticles were prepared via ionic gelation technique with 83.65 ± 3.12% yield. Microparticles were evaluated based on drug release profile, drug degradation, permeation, mucoadhesion, β-lactamase inhibition, in vitro antimicrobial activity, in vivo gastro retention, in vivo gastroprotection and in vitro cytotoxicity parameters to ensure their therapeutic outcomes.

In silico investigation predicted higher binding affinity (− 5.752 kcal/mol) of phytic acid with β-lactamase enzyme than clavulanic acid (− 4.870 kcal/mol). The microparticles that demonstrated 85.21 ± 1.12% entrapment efficiency and good mucoadhesive profile (~ 40%) showed high gastric stability and sustained release profile (~ 82% release in 14 h). SEM examination portrayed non-spherical particles with porous surfaces. FTIR and DSC analyses revealed no interaction between the drug and the polymer matrix. Microparticles were found to have superior β-lactamase inhibition potential and higher zone of inhibition (27.66 ± 2.49 mm)) compared with pure drug (18.33 ± 1.69). X-ray radiography study indicated that the prepared microparticles retained in the stomach for over 4 h.

In conclusion, provided with tremendous improvement in the drug’s stability in the gastric environment, these microparticles pose a viable option in the treatment of H. pylori infections.