Amoxicillin-docosahexaenoic acid encapsulated chitosan-alginate nanoparticles as a delivery system with enhanced biocidal activities against Helicobacter pylori and improved ulcer healing

Abstract

Encapsulation of amoxicillin (AMX) for drug delivery against Helicobacter pylori infection and aspirin-induced ulcers in rat’s stomachs was performed using docosahexaenoic acid (DHA)-loaded chitosan/alginate (CA) nanoparticles (NPs) developed by ionotropic gelation method. The physicochemical analyses of the composite NPs were performed by scanning electron microscopy, Fourier transform infrared spectroscopy, zeta potential, X-ray diffraction, and atomic force microscopy. The encapsulation efficiency of AMX was increased to 76% by incorporating DHA, which resulted in a reduction in the particle size. The formed CA-DHA-AMX NPs effectively adhered to the bacteria and rat gastric mucosa. Their antibacterial properties were more potent than those of the single AMX and CA-DHA NPs as demonstrated by the in vivo assay. The composite NPs attained higher mucoadhesive potential during food intake than during fasting (p = 0.029). At 10 and 20 mg/kg AMX, the CA-AMX-DHA showed more potent activities against H. pylori than the CA-AMX, CA-DHA, and single AMX. The in vivo study showed that the effective dose of AMX was lower when DHA was included, indicating better drug delivery and stability of the encapsulated AMX. Both mucosal thickening and ulcer index were significantly higher in the groups receiving CA-DHA-AMX than in the groups receiving CA-AMX and single AMX. The presence of DHA declines the pro-inflammatory cytokines including IL-1β, IL-6, and IL-17A. The synergistic effects of AMX and the CA-DHA formulation increased the biocidal activities against H. pylori infection and improved ulcer healing properties.

Antibacterial and Immunoregulatory Effects of Metformin against Helicobacter pylori Infection in Rat Model

“…However, metformin can be used as an adjuvant to reduce the effective dose of AMX. We have previously reduced the effective dose of this antibiotic by encapsulation with chitosan and docosahexaenoic acid [ 31 ].…”

Helicobacter pylori infection in humans and phytotherapy, probiotics, and emerging therapeutic interventions: a review

“…Nanoparticles supplemented with 2% (v/v) DHA significantly hindered the growth of H. pylori compared to the control group (no nanoparticles added). Moreover, the inclusion rate of antibiotics increased to 76 percent after the addition of this fatty acid ( Khoshnood et al, 2023 ). In vivo , fucus-chitosan/heparin nanoparticle delivery systems significantly increased the ability to inhibit H. pylori compared to conventional antibiotic therapy.…”

Chitosan/Alginate-Based Nanoparticles for Antibacterial Agents Delivery

“… [ 110 ] Amoxicillin Oil-in-water emulsification combined with ionic gelation method In vivo Helicobacter pylori Growth inhibition rate level: AMX-loaded NPs > Blank NPs The incorporation of amoxicillin into nanoparticles enhances its antibacterial effects compared to conventional amoxicillin due to increased drug bioavailability. [ 111 ] Amoxicillin Ionotropic pre-gelation combined with polyelectrolyte complexation method Helicobacter pylori In vivo mucopenetration studies revealed that amoxicillin-loaded NPs exhibit higher percentage drugs accumulated than free amoxicillin The nanoparticle formulation helps amoxicillin in maintaining its stability during adhesion process in gastric juice environment. It also increase uptake of amoxicillin into gastric mucosa due to reduced particle size.…”

“…It also increase uptake of amoxicillin into gastric mucosa due to reduced particle size. [ 119 ] Amoxicillin (AMX) combined with docosahexaenoic acid (DHA) Oil-in-water emulsification combined with ionic gelation method In vivo Helicobacter pylori Growth inhibition rate level: AMX-DHA-loaded NPs > AMX-loaded NPs > DHA-loaded NPs > Blank NPs The system is capable of loading multiple components, providing additive properties from the addition of DHA [ 111 ] Enrofloxacin Ionic gelation method In vitro and in vivo Escherichia coli MIC: Free Enrofloxacin = 1 µg/mL Enrofloxacin-loaded NPs = 0.125 µg/mL Drug delivery in the nano-system protects the drug from negative exposure, thereby indirectly increasing efficacy. [ 112 ] Doxycycline Ionotropic Gelation Method In vitro Proteus mirabilis, Escherichia coli , and Enterococcus faecalis Inhibition rate: Doxycycline-loaded NPs > Blank NPs > Free Doxycycline > Negative Control Synergistic effects arise from the nano-charge of alginate guided by non-ionic interactions between chitosan and bacterial peptidoglycan teichoic acid.…”

“… 118 In such cases, the oil-in-water emulsification method proves more suitable for manufacturing such medications. 111 Moreover, evidence underscores the prevalence of the ionic gelation method due to its straightforwardness. Selecting the drug’s base or salt form is also critical to ensure optimal compatibility with alginate and chitosan.…”