Preparation, characterization and in vitro antimicrobial activity of metronidazole bearing lectinized liposomes for intra-periodontal pocket delivery.
Liposomes constructed of egg phosphatidylcholine (EPC), cholesterol (Chol) and stearoylamine (SA) were coated with lectin (Concanavalin-A). These lectinized liposomes were found to retain the ligand binding activity of surface coated concanavalin A (Con-A) as demonstrated by bovine submaxillary mucin (BSM) binding assay. Moreover the ligand specificity of Con-A was maintained even after coating the liposome surface because the presence of competing sugar alpha-methyl mannoside, significantly inhibited the interaction of lectinized liposomes and BSM. The significance of divalent cations for these interactions was studied. The Con-A coating was found to be stable in simulated salivary fluids (SSF, pH 7.2) and under various pH conditions. In vitro targeting studies of lectinized liposomes with gram-negative bacilli (Streptococcus mutans) that harbor in the periodontal pocket (biofilm) demonstrated nearly 100% bacterial growth inhibition (% BGI). The antimicrobial effect was maintained for 360 min. The results were compared with metronidazole bearing plain (protein free/uncoated) liposomes and the free drug at the same dose levels. Mechanisms involved are also discussed. These observations suggest that liposomes coated with lectin (Con-A) were able to maintain the sugar affinity and specificity of the associated ligand and could be targeted to the surface 'glyco-calyx' of bacterial bio-film.
Vyas
S P
SP
Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Vishvavidyalaya, Sagar, M.P., India. spvyas@bom6.vsnl.net.in
Sihorkar
V
V
Dubey
P K
PK
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D003208:Concanavalin A; D004337:Drug Carriers; D004355:Drug Stability; D005079:Excipients; D006863:Hydrogen-Ion Concentration; D037102:Lectins; D008081:Liposomes; D008795:Metronidazole / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D009997:Osmotic Pressure; D010316:Particle Size; D010519:Periodontium; D013295:Streptococcus mutans / Q000187:drug effects
D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D005079:Excipients; D037102:Lectins; D008081:Liposomes; D003208:Concanavalin A; D008795:Metronidazole