Evaluation of cross-linked chitosan microparticles containing metronidazole for periodontitis treatment.

The aims of this study were to find the optimal formulation for the preparation of metronidazole-loaded chitosan microparticles (MTZ-MPs) via an emulsion cross-linking process, and to compare the in vitro release of MTZ from hydrogels and films containing the drug in forms of MTZ-MPs and raw powders. The effects of emulsifier type and concentration, amount of cross-linking agent, cross-linking time, drug:chitosan ratio, form of drug adding and washing method on the properties of the MTZ-MPs were investigated. The results indicated that the optimal conditions for round and free-flowing MTZ-MPs with a high percentage of entrapped drug and preferable release profile were 1% of Span80 in soybean oil, 5% of glutaraldehyde based on chitosan solution, 30 min of cross-linking time, 1:1 drug:chitosan ratio, drug adding in form of ethanol solution and washing with hexane only. MTZ-MPs prepared from the optimal formulation were incorporated in mucoadhesive hydrogel and film. The release profiles of the drug from hydrogel and film containing MTZ-MPs were in prolong pattern compared with those containing drug powders. However, the hydrogels exhibited higher preferable pattern of release profile than the films. Therefore, the hydrogel containing MTZ-MPs was possible to be further clinically investigated for peridontitis treatment.