Lectin Conjugated Gastroretentive Multiparticulate Delivery System of Clarithromycin for the Effective Treatment of Helicobacter pylori

Abstract

The aim of the research work was to develop and characterize a concanavalin-A (Con-A) conjugated gastroretentive multiparticulate delivery system of clarithromycin (CM) for the effective treatment of colonization of Helicobacter pylori (H. pylori). Ethylcellulose (EC) microspheres containing CM were prepared using emulsification/ evaporation method. Formulations were characterized for micromeritic properties, % drug entrapment, % yield, surface morphology, buoyancy behavior and in vitro drug release in simulated gastric fluid. EC microspheres of CM were conjugated with Con-A. IR spectroscopy and differential scanning calorimetry were used to confirm conjugation of Con-A to EC microspheres while Con-A conjugated microspheres were further characterized using the parameters of zeta potential, mucoadhesiveness to gastric mucosa and Con-A conjugation efficiency with microspheres. The gamma scintigraphy of the formulations was carried out in albino rabbits (New Zealand) to monitor the transit of Con-A conjugated EC microspheres and marketed formulation in gastrointestinal (GI) tract. The microparticles were found to be regular and spherical in shape. The particle size of microspheres was found to vary from 112.45 +/- 3.39 to 124.23 +/- 2.31 microm with polymer concentration from 1% w/v to 3% w/v. IR and DSC studies confirmed the attachment of Con-A with EC microspheres. All the microsphere formulations showed good % drug entrapment (70 +/- 3%). Zeta potential of EC microspheres and Con-A conjugated EC microspheres was found to be -8.77 +/- 0.5 mV and 7.56 +/- 0.7 mV, respectively. Maximum mucoadhesion (85 +/- 2.6%) was shown by Con-A conjugated EC microspheres as compared with nonconjugated EC microspheres (12.0 +/- 3.2%). Performance of developed formulation in GI tract was visualized successfully by gamma scintigraphy in rabbits. Prolonged gastric residence time (GRT) of over 6 h was achieved in all rabbits for Con-A conjugated microspheres of CM. It is concluded that designed targeted delivery system could possibly treat the colonization of H. pylori.