Delivering amoxicillin at the infection site – a rational design through lipid nanoparticles

Daniela Lopes-de-Campos,1,* Rita M Pinto,1,* Sofia A Costa Lima,1 Tiago Santos,2,3 Bruno Sarmento,2–4 Cláudia Nunes,1 Salette Reis1 1LAQV, REQUIMTE, Departamento de Ciáncias Químicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; 2INEB – Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal; 3i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; 4IINFACTS, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde, Gandra, Portugal *These authors contributed equally to this work Purpose: Amoxicillin is a commonly used antibiotic, although degraded by the acidic pH of the stomach. This is an important limitation for the treatment of Helicobacter pylori infections. The purpose of this work was to encapsulate amoxicillin in lipid nanoparticles, increasing the retention time at the site of infection (gastric mucosa), while protecting the drug from the harsh conditions of the stomach lumen.Materials and methods: The nanoparticles were produced by the double emulsion technique and optimized by a three-level Box-Behnken design. Tween 80 and linolenic acid were used as potential therapeutic adjuvants and dioleoylphosphatidylethanolamine as a targeting agent to Helicobacter pylori. Nanoparticles were characterized regarding their physico-chemical features, their storage stability, and their usability for oral administration (assessment of in vitro release, in vitro cell viability, permeability, and interaction with mucins).Results: The nanoparticles were stable for at least 6 months at 4°C. In vitro release studies revealed a high resistance to harsh conditions, including acidic pH and physiologic temperature. The nanoparticles have a low cytotoxicity effect in both fibroblasts and gastric cell lines, and they have the potential to be retained at the gastric mucosa.Conclusion: Overall, the designed formulations present suitable physico-chemical features for being henceforward used by oral administration to treat Helicobacter pylori infections. Keywords: linolenic acid, dioleoylphosphatidylethanolamine, Box-Behnken design, permeability, mucins, Helicobacter pylori