Targeting and killing the Ever-Challenging ulcer bug

Daniela Lopes-de-Campos1, Catarina Leal Seabra2, Rita M Pinto1

  • 1LAQV, REQUIMTE, Departamento de Ciencias Químicas, Faculdade de Farmacia, Universidade do Porto, Portugal.

Insights

Novel amoxicillin-loaded lipid nanoparticles effectively target and eliminate Helicobacter pylori infections. This advanced nanosystem overcomes gastrointestinal barriers and enhances stomach retention, offering a promising strategy against the ulcer-causing bacteria.

Area of Science:

  • Nanotechnology
  • Microbiology
  • Gastroenterology

Background:

  • Helicobacter pylori infections are a persistent challenge, contributing to gastric cancer due to ineffective antibiotic delivery.
  • Current treatments struggle to achieve adequate antibiotic concentrations at the infection site.

Purpose of the Study:

  • To develop amoxicillin-loaded lipid nanoparticles for enhanced H. pylori treatment.
  • To evaluate the nanoparticles' targeting, bacteria-killing, and gastrointestinal barrier-overcoming capabilities.
  • To assess the potential of a stomach-retention floating system for nanoparticle delivery.

Main Methods:

  • Development of lipid nanoparticles using DOPE, Tween®80, and linolenic acid.
  • Evaluation of bacterial targeting and adhesion inhibition using imaging flow cytometry and cell models.
  • Assessment of antibacterial efficacy through time-kill kinetics, SEM, and membrane permeability studies.
  • Testing in a novel in vitro gastrointestinal infection model and incorporation into a floating system.

Main Results:

  • Nanoparticles demonstrated effective bacterial targeting and inhibition of adhesion to gastric cells.
  • An antibiotic-free strategy was shown to kill H. pylori, confirmed by membrane permeability studies.
  • The nanosystem successfully overcame physical and chemical gastrointestinal barriers.
  • Incorporation into a floating system increased potential stomach retention time.

Conclusions:

  • The developed amoxicillin-loaded lipid nanoparticles represent an effective nanosystem for combating H. pylori infections.
  • The study introduces innovative tools: an in vitro infection model and a nanoparticle-based floating system with broader applications.

Related Concept Videos

Treating Helicobacter pylori in Peptic Ulcers: Antimicrobial Therapy01:16

Treating Helicobacter pylori in Peptic Ulcers: Antimicrobial Therapy

Helicobacter pylori, a resilient gram-negative bacterium, can thrive in the stomach's harsh, acidic environment. Infection with H. pylori leads to a cascade of events within the stomach lining. One of the critical disruptions caused by this bacterium is the interference with somatostatin production, a hormone responsible for regulating acid secretion. This interference tips the balance, escalating acid secretion and diminishing bicarbonate levels. This imbalance compromises the defensive...
603
Acid Suppressive Drugs for Peptic Ulcer Disease: Proton Pump Inhibitors01:13

Acid Suppressive Drugs for Peptic Ulcer Disease: Proton Pump Inhibitors

Peptic ulcers, often induced by H. pylori infections or NSAID usage, arise from disruptions in the delicate balance of gastric acid production. Peptic ulcers stem from heightened gastric acid levels due to H. pylori infections or NSAID use. The protective mucus layer diminishes in the presence of these factors, allowing gastric acid to erode the stomach lining and form ulcers.
Gastric acid, a potent cocktail of hydrogen and chloride ions, is produced in specialized parietal cells within the...
561
Peptic Ulcer Disease IV: Management01:26

Peptic Ulcer Disease IV: Management

Medical treatment strategies for peptic ulcers encompass various methods. The primary goal of treatment is to diminish gastric acidity and strengthen mucosal defense mechanisms.
The therapeutic approach involves ensuring adequate rest, implementing drug therapy, promoting smoking cessation, making dietary modifications, and emphasizing long-term follow-up care.
Pharmacological management
The prevailing therapy for peptic ulcers involves a combination of managing the patient's current...
155
Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists01:28

Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists

Histamine H2 receptors, which are intricately located on the basolateral membrane of parietal cells, play a crucial role in modulating gastric acid secretion. When released from enterochromaffin-like cells, histamine engages H2 receptors, initiating the cyclic AMP (cAMP) pathway. In this pathway, adenylyl cyclase converts ATP into cAMP, elevating intracellular cAMP levels. The activation of protein kinase A follows, stimulating the proton pump. This stimulation prompts the secretion of hydrogen...
597
Pathophysiology of Peptic Ulcer Disease: Injurious Factors01:22

Pathophysiology of Peptic Ulcer Disease: Injurious Factors

Peptic ulcers are sores on the stomach's inner lining and the upper small intestine, which are the result of disruptions in the mucosal layer that houses parietal cells which produce gastric acid, and chief cells which secrete pepsinogen.
In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds...
767
Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors01:24

Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors

Peptic ulcer disease, commonly called PUD, represents a multifaceted condition characterized by disruptions in the lining of the gastrointestinal (GI)  tract. Central to the protection of the gastrointestinal lining is the mucosal-bicarbonate barrier. This physiological defense mechanism is a formidable shield against the corrosive effects of gastric acid and pepsin secretion in the stomach. Its role is pivotal in maintaining the structural integrity of the stomach's inner lining.
638