Drug Release Kinetics, Biodegradability, Antimicrobial Activity and Cytotoxicity of 2% Minocycline-Loaded PoIysaccharide Microcapsules

미노싸이클린 함유 폴리사카라이드 미소캡슐의 약물방출능, 생분해성, 항균력 및 세포독성 연구

Backround : To achieve optimal drug delivery rate and duration to a specific target site with desirable biodegradability of the drug carriers in the intended time period, 2% minocycline-HCl loaded microcapsule composed of alginate and chitosan were fabricated. Methods : Microcapsule were designed to maintain drug concentration in the intra-crevicular for 1 week. In vitro drug release experiments of 2% minocycline-HCI loaded microcapsules was performed in the simulated gingival crevicular fluid. In vivo biodegradability and release kinetics were evaluated by inserting 50mg of microcapsule into the pocket. The fluid concentration upto 7 days was checked by agar diffusion assay with Periopaper. And all the remnant was collected by washing technique and id biodegradability was examined by SEM. Antimicrobial activity of drug loaded microcapsules was ascertained by agar dilution and diffusion method. Cytotoxicity was investigated by MTT test to examine on the effect of drug-loaded and un-loaded microcapsule on cellular activity of gingival fibroblast. Results : In vitro and vivo drug release of the microcapsules showed zero order release kinetics with initial burst effects. The in vivo release rate was shown to $540{\mu}g$ in first 24 hours and gradually diminished of $9{\mu}g$ in 7days. in vivo biodegradability showed demolished shape of microcapsule at 7 days of insertion. Cytotoxicity of drug-loaded and un-loaded microcapsule showed no significant inhibitory effect on the growth of gingival fibroblast. Minocycline releasing media from 1 day to 7 days of release experiments showed sufficient microbial growth inhibitory activity. Conclusion : These results suggested that 2% chitosan-alginate microcapsule might be ideal tool for local drug delivery system for treatment of periodontal disease.

배 경 : 항균제를 치주낭에 직접투입하여 일정한 속도로 일정 기간동안 약물을 송달하며 치료후 생분해성을 획득할 수 있는 제제로서 알긴산 나트륨과 키토산으로 이루어진 미노싸이클린 함유미소캡슐을 연구하였다. 방 법: 알긴산나트륨과 키토산으로 미소캡슐을 제조한 후 약물을 봉입하였으며 제조된 약물 함유 미소캡슐에 대해 약물용출실험 세포독성 실험, 항균력 실험, 치주낭내에서의 약물 용출실험, 생분해 실험을 수행하였다. 결 과 : 약물의 방출은 초기 속방출이후 일정속도를 유지하였다. 치주낭내에서는 24시간후 $540{\mu}g$이 용출된 후 서서히 약물을 용출하여 7일 후 $9{\mu}g$을 방출시켰다. 생분해 실험 결과 치주낭에서 7일 후에는 미소캡슐이 분해되어 형체가 소실되었다. 약물함유 및 비함유 미소캡슐 모두 치주섬유아세포에 대한 유의할만한 독성은 보이지 않았으며 일별 용출된 약물은 모두 높은 항균력을 나타내었다. 결 론 : 이상의 결과로 미노싸이클린 함유 미소캡슐은 치주질환치료에 유용한 제제로서의 활용성이 제시되었다.