Lectin Conjugated Gastroretentive Multiparticulate Delivery System of Clarithromycin for the Effective Treatment of Helicobacter pylori Sunil K. Jain* and Manmohan S. Jangdey SLT Institute of Pharmaceutical Sciences, Guru Ghasidas UniVersity, Bilaspur (C.G.) 495 009, India Received October 6, 2008; Revised Manuscript Received November 23, 2008; Accepted December 3, 2008 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. Formula- tions 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 Zeeland) 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 µm 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. Keywords: Clarithromycin; concanavalin-A; mucoadhesive drug delivery system; microspheres; gamma scintigraphy Introduction Helicobactor pylori (H. pylori) is a small, spiral, mi- croaerophilic, Gram-negative bacteria with a 4-6 bulbous tipped sheathed flagella at one end, which helps it to penetrate the gastric mucosa and colonize on the gastric antrum. 1,2 The organism exclusively remains on the luminal surface of the gastric mucosa under the mucus gel layer, and access * Address correspondence to this author. Mailing address: Guru Ghasidas University, SLT Institute of Pharmaceutical Sciences, Bilaspur (C.G.) 495 009, India. Phone: 094254 52174. Fax: 07752 260148. E-mail: suniljain25in@yahoo.com. (1) Warren, J. R.; Marshall, B. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983, 1, 1273–1275. (2) Umamaheswari, R. B.; Jain, S.; Tripathi, P. K.; Jain, N. K. Floating-bioadhesive microspheres containing acetohydroxamic acid for clearance of Helicobacter pylori. Drug DeliVery 2002, 9 (4), 223–231. articles 10.1021/mp800193n CCC: $40.75  2009 American Chemical Society VOL. 6, NO. 1, 295–304 MOLECULAR PHARMACEUTICS 295 Published on Web 12/18/2008