title: Receptor-mediated targeting of lipobeads bearing acetohydroxamic acid for eradication of Helicobacter pylori.
abstract: In the present context, phosphatidyl ethanolamine (PE) liposomes anchored polyvinyl alcohol (PVA) xerogel beads (lipobeads) bearing acetohydroxamic acid (AHA) was developed as a receptor-mediated drug delivery system for use in blocking adhesion of Helicobacter pylori and thereby preventing the sequelae of chronic gastric infections. PVA beads containing AHA were prepared by emulsification followed by low temperature crystallization method. Surface acylation with fatty acid chain was accomplished by treating PVA bare beads with palmitoyl chloride. The completion of this reaction was characterized by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) which confirmed the formation of an ester bond. Final formation of lipobeads was accomplished by combining acylated PVA beads with a PE liposome suspension. To confirm the specific binding propensity of lipobeads towards the PE specific surface receptors of H. pylori, we have performed in situ adherence assay and radiolabelling assay with human stomach cells and KATO-III cells, respectively. In both of these studies, pretreatment of H. pylori with lipobeads completely inhibited the adhesion of H. pylori to human stomach cells and KATO-III cells. These assays could serve as suitable in-vitro models for the study of binding efficacy of lipobeads with H. pylori surface receptors. In addition, the antimicrobial activity of the formulations was evaluated by growth inhibition (GI) studies with isolated H. pylori strain. The inhibitory efficacy of lipobeads was significantly higher compared to that of PVA bare beads. These results suggest that lipobeads could be a potential targeted drug delivery system in the treatment of H. pylori.
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar (M.P.) 470 003, India.
authors.forename: R B
authors.initials: RB
authors.lastname: Umamaheshwari
authors.forename: N K
authors.initials: NK
authors.lastname: Jain
mesh_terms: D001422:Bacterial Adhesion / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods; D041981:Gastrointestinal Tract / Q000166:cytology / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D066298:In Vitro Techniques; D008081:Liposomes / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000737:chemistry; D013997:Time Factors; D014510:Urease / Q000037:antagonists & inhibitors*
chemical_list: D006877:Hydroxamic Acids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011956:Receptors, Cell Surface; C006358:acetohydroxamic acid; D011142:Polyvinyl Alcohol; D014510:Urease