Amoxicillin and Clarithromycin Mucoadhesive Delivery System for Helicobacter pylori Infection in a Mouse Model: Characterization, Pharmacokinetics, and Efficacy

Abstract

Helicobacter pylori is the main pathogen responsible for gastric ulcers and a predisposing factor of stomach cancer. Although current treatment is usually successful, it requires high doses and frequent administration. An innovative mucoadhesive system (Mucolast®) loaded with amoxicillin and clarithromycin is proposed to improve the efficacy of treatment against H. pylori. The drug product was optimized based on its viscoelastic properties to obtain long-term stability of the vehicle. The drug release mechanisms were different for both antibiotics based on their solubilization status. A systemic and stomach pharmacokinetic profile was obtained after three different doses were administered to mice, obtaining similar systemic exposure levels but an increase in drug concentration in the stomach. The efficacy results in mice infected with H. pylori also demonstrated the superiority of the antibiotics when administered in Mucolast®, as shown by the bacterial count in stomach tissue and under histopathological and biochemical evaluation. The proposed treatment was efficacious and safe and is presented as a realistic alternative to current treatment options to improve patient compliance and to reduce bacterial resistance.

Animal Models and Helicobacter pylori Infection

“…Several other studies have also attempted to potentiate the efficacy of existing antibiotics by combining them with other compounds, as the current treatment usually requires high doses and frequent administration to succeed. A similar study proposed that an innovative mucoadhesive system (Mucolast ® ) loaded with amoxicillin and clarithromycin could improve the efficacy of treatment against H. pylori [ 166 ]. Treatment of H. pylori -infected C57BL/6 mice with Mucolast ® loaded with antibiotics showed superior efficacy than treatment with antibiotics only, as evidenced by the bacterial count in stomach tissues and histopathological evaluations.…”

Scope and Limitations of Current Antibiotic Therapies against Helicobacter pylori: Reviewing Amoxicillin Gastroretentive Formulations

“…Mucoadhesive polymers such as chitosan (CTS), pectin, Carbopol ® , polyacrylic acid (PAA), and sodium carboxymethylcellulose (NaCMC) were reported as materials of interest in the preparation of mucoadhesive GRDDSs, as well as gums such as guar gum, gellan gum, and xanthan gum, and thiolated polymers, among others (Table 3). Polycarbophil ® [101] NaCMC [104] Anionic polysaccharides and gums NaAlg [98,105] Pectin [106,107] Gellan gum [90] Xanthan gum [105,108] Other polysaccharides and gums…”

“…The first one (ionic gelation method) is based on the electrostatic interaction between a cationic polymer (CTS [ 98 , 104 ] or its derivatives [ 110 ]) with an anionic polysaccharide, typically NaAlg [ 98 , 104 ], PAA [ 100 ], sodium carboxymethylcellulose (NaCMC [ 104 ]), pectin [ 106 ], or poly(malic acid) [ 110 ]. Since anionic polymers are polycarboxylic materials, Ca 2+ ions from CaCl 2 or CaSO 4 can be added to improve the overall stability of the formulations [ 98 , 104 , 105 ]. Similarly, sulfate anions from Na 2 SO 4 or CaSO 4 are employed to strengthen CTS-based GRDDSs [ 98 , 105 ].…”

“…Since anionic polymers are polycarboxylic materials, Ca 2+ ions from CaCl 2 or CaSO 4 can be added to improve the overall stability of the formulations [ 98 , 104 , 105 ]. Similarly, sulfate anions from Na 2 SO 4 or CaSO 4 are employed to strengthen CTS-based GRDDSs [ 98 , 105 ]. CTS is frequently employed as a coating agent [ 98 , 104 ].…”

“…Mucoadhesive performance is commonly measured on model mucosae (goat intestinal mucosa [ 109 ], pig’s ileum [ 98 ], or rat stomach mucosa [ 99 , 102 , 103 ]) or on freshly prepared simulated gastric mucosa [ 105 ]. In another study [ 88 ], Wistar rats were employed to study in vivo gastric mucoadhesion.…”