ethyl-cellulose and Helicobacter-Infections

Using second generation mucoadhesives may enhance targeting antibiotics for eradication of Helicobacter pylori from the stomach for the treatment of peptic ulcer. The aim of this research was to prepare and characterise ethylcellulose/chitosan microspheres containing clarithromycin with their surfaces functionalised with concanavalin A to produce a floating-mucoadhesive formulation. The microspheres were prepared using an emulsification-solvent evaporation method. Particle size, surface morphology, in vitro buoyancy profile, zeta potential, drug entrapment efficiency, in vitro drug release and release kinetics of the particles were determined. Lectin was conjugated to the microsphere surface using two-stage carbodiimide activation and confirmed using FTIR, fluorescence studies and zeta potential measurements. Conjugation ranged from 11 to 15 μg Con A/mg microspheres which represents over 56% efficiency although there was some drug loss during the conjugation process. Conjugation did not have a significant effect on the buoyancy and release of drug from the microspheres using a mucus diffusion model with 53% and 40% of drug released from unconjugated and conjugated microspheres within 12h. Conjugation improved mucoadhesion and interaction with porcine gastric mucin compared to unconjugated microspheres. The buoyancy and improved mucoadhesion of the microspheres provides potential for delivery of clarithromycin and other drugs to the stomach.

Topics: Adhesiveness; Animals; Anti-Bacterial Agents; Cellulose; Chitosan; Clarithromycin; Concanavalin A; Diffusion; Drug Stability; Gastric Juice; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Membranes, Artificial; Microspheres; Mucins; Mucus; Powder Diffraction; Spectroscopy, Fourier Transform Infrared; Swine; X-Ray Diffraction

The extreme acidic environment of the stomach, its regular voidance of contents and the restricted access to the mucus covered habitat combined with the antibiotic resistance of the bacteria, all contribute to the poor success in the treatment of Helicobacter pylori gastric infections. Here, we demonstrate that by encapsulating clarithromycin into ethyl cellulose (EC) nanoparticles, the efficiency of H. pylori clearance in C57BL/6 mice infected with these bacteria was significantly improved. Clarithomycin-loaded EC nanoparticles were prepared via a simple yet effective anti-solvent particle induction method, to yield sub-micron sized particles with 22.3 ± 0.17% (w/w) clarithromycin loading at 86 ± 0.5% (w/w) encapsulation efficiency. The particles dispersed well in water and simulated gastric fluid and gave a minimum inhibitory concentration of 0.09-0.18 μg/ml against four strains of H. pylori. Encapsulation into EC particles not only enhanced the anti-adhesion activity of clarithromycin when tested with H. pylori and Hep-2 cells, but also gave significant enhancement of H. pylori clearance in the stomach of C57BL/6 mice infected with the bacteria.

Topics: Animals; Anti-Bacterial Agents; Bacterial Adhesion; Cell Line, Tumor; Cellulose; Clarithromycin; Female; Helicobacter Infections; Helicobacter pylori; Male; Mice, Inbred C57BL; Microbial Sensitivity Tests; Nanocapsules; Stomach

Helicobacter pylori reside in the gastric mucus layer and at the mucus-epithelial cell interface wherein access of antimicrobial drug to the infection site is restricted both from the stomach and from the gastric blood supply. The aim of the present study was to develop pectin or gellan gum blended sodium alginate microspheres in order to eradicate gastric Helicobacter pylori. The percentage drug release and mucoadhesion were decrease on increasing the calcium chloride in the formulation dispersion. Curing time significantly effected encapsulation efficiency and was not affected % drug content, % buoyancy, and particle size and drug release. The efficacy of the optimized formulation was evidenced by absence of amplified bacterial gene in treated stomach tissue of Mongolian gerbils as observed using in polymerase chain reaction. The results demonstrate that the developed formulation of Am has potential to eradicate Helicobacter pylori by targeted and prolonged retention at gastric mucosa.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Bacterial Load; Cellulose; Delayed-Action Preparations; Drug Delivery Systems; Gastric Mucosa; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Hydrogen-Ion Concentration; Male; Microspheres; Particle Size; Rats; Solubility; Surface Properties

The objective of the study was to develop a stomach-specific drug delivery system for controlled release of clarithromycin for eradication of Helicobacter pylori (H. pylori). Floating-bioadhesive microspheres of clarithromycin (FBMC) were prepared by emulsification-solvent evaporation method using ethylcellulose as matrix polymer and Carbopol 934P as mucoadhesive polymer. The prepared microspheres were subjected to evaluation for particle size, incorporation efficiency, in vitro buoyancy, in vitro mucoadhesion and in vitro drug release characteristics. The prepared microspheres showed a strong mucoadhesive property with good buoyancy. The formulation variables like polymer concentration and drug concentration influenced the in vitro drug release significantly in simulated gastric fluid (pH. 2.0). The in vivo H. pylori clearance efficiency of prepared FBMC in reference to clarithromycin suspension following repeated oral administration to H. pylori infected Mongolian gerbils was examined by polymerase chain reaction (PCR) technique and by a microbial culture method. The FBMC showed a significant anti-H. pylori effect in the in vivo gerbil model. It was also noted that the required amount of clarithromycin for eradication of H. pylori was significantly less in FBMC than from corresponding clarithromycin suspension. The results further substantiated that FBMC improved the gastric stability of clarithromycin (due to entrapment within the microsphere) and eradicated H. pylori from the gastrointestinal tract more effectively than clarithromycin suspension because of the prolonged gastrointestinal residence time of the formulation.

Topics: Acrylic Resins; Adhesives; Animals; Anti-Infective Agents; Cellulose; Chemistry, Pharmaceutical; Clarithromycin; DNA, Bacterial; Drug Compounding; Excipients; Gastric Juice; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Hydrogen-Ion Concentration; Kinetics; Male; Microscopy, Electron, Scanning; Microspheres; Particle Size; Polyvinyls; Reverse Transcriptase Polymerase Chain Reaction