1-하이드록시-2-나프톤산 첨가를 통한 PLGA 미립구로부터 에스시탈로프람의 서방출 = Sustained release of escitalopram from PLGA microsphere with addition of 1-Hydroxy-2-naphthoic acid.

국문 초록 (Abstract)

에스시탈로프람은 선택적 세로토닌 흡수 억제제로 우울증 및 강박증 환자들에게 널리 처방되고 있다. 우울증 환자들의 경우, 짧게는 몇 달에서 길게는 몇 년 동안 우울증 치료제를 매일 복용해야 하는 불편함이 있다. 따라서 우리는 다회투여로 인한 환자의 피로도를 줄이기 위하여 에스시탈로프람을 PLGA 미립구 제제를 이용한 서방형 주사제로 개발하고자 하였다.
생분해성 고분자인 PLGA로 제조된 미립구는 약물 방출 후에 체내로부터 제거할 필요가 없기 때문에 많은 관심이 되어 왔지만, 초기에 급작스러운 방출이 나타나는 등 방출속도 제어에 어려움이 많다. 에스시탈로프람 역시 오로지 약물만을 봉입한 PLGA 미립구의 경우 7일 만에 모든 약물이 방출되었다. 본 연구에서는 이러한 한계를 극복하기 위하여 1-Hydroxy-2-naphthoic acid와 에스시탈로프람을 다양한 조건으로 PLGA 미립구에 봉입하여 서방출 되는 최적의 조건을 찾고자 하였으며, scanning electron microscope 이미지 분석, 미립구의 평균입자 크기 측정, PBS에서의 미립구의 거동관찰, 봉입효율, 로딩효율, 수율 측정, differential scanning calorimetry 분석, in vitro release test, in vivo release test를 진행하였다. 그 결과, 1-Hydroxy-2-naphthoic acid는 PLGA 미립구에서 약물과 PLGA 간의 분자 간 상호작용을 통해 결합력을 형성하였고, 1-Hydroxy-2-naphthoic acid의 첨가 비율이 증가할수록 약물 방출 속도가 지연되는 효과가 있었다.
결과적으로 이번 연구를 통해 에스시탈로프람의 봉입율과 로딩율을 증가시킬 뿐만 아니라 약물이 서방출 될 수 있는 최적의 제형을 확립하였다. 이는 에스시탈로프람을 전달하는 효과적인 약물전달체로서 큰 잠재력을 갖고 있으며 우울증 치료에 효과적으로 이용될 수 있을 것이다.

다국어 초록 (Multilingual Abstract)

Escitalopram is a selective serotonin uptake inhibitor widely prescribed for patients with depression and obsessive-compulsive disorder. In patients with depression, there is the inconvenience of taking antidepressant medication daily for months to years. Therefore, we tried to develop escitalopram, a treatment for depression, as sustained-release injections using PLGA microsphere formulation to reduce patient's inconvenience due to multi-dose administration.
PLGA microspheres, which are biodegradable polymers, have been of great interest since they do not need to be removed from the body after drug release, but there are many difficulties in controlling the release rate, such as sudden release at the beginning. In the case of PLGA microspheres containing only escitalopram, all the drugs are released within 7 days. In order to overcome these limitations, we tried to find out the optimal formulations for escitalopram release by incorporating 1-Hydroxy-2-naphthoic acid and escitalopram into PLGA microspheres under various conditions. We performed scanning electron microscope image analysis, measurement of average particle size of microspheres, observation of microspheres behavior in PBS, encapsulation efficiency measurement, loading efficiency measurement, yield measurement, differential scanning calorimetry analysis, in vitro release test and in vivo release test. As a result, by loading 1-Hydroxy-2-naphthoic acid to PLGA microspheres formed binding force between drug and PLGA. Moreover the drug release rate was delayed as the addition ratio of 1-Hydroxy-2-naphthoic acid increased.
   As a result, this study did not only increased the encapsulation efficiency and loading content of escitalopram, but also developed the optimal formulation for drug release. It has great potential as an effective drug delivery system for delivering escitalopram and is expected to be useful in the treatment of depression.

목차 (Table of Contents)

• 초록 ························································
• 목차 ························································
• 그림 , 표 목차 ·············································
• Ⅰ. 서론 ····················································
• 1.
• 서방형 제제 ·······································
• 2.
• 생분해성 고분자 미립구 ···························
• 3.
• 우울증 및 치료제 ··································
• 4.
• 에스시탈로프람 ····································
• Ⅱ. 재료 및 실험방법 ·····································
• 1.
• 시약 및 재료 ·····································
• 2.
• PLGA 미립구의 제조 ····························
• 3.
• PLGA 미립구의 물리적 특성 ····················
• 4.
• PLGA 미립구의 형태학적 특성 ··················
• 5.
• PLGA 미립구로부터 약물 방출 특성 ············
• Ⅲ. 결과 및 고찰 ··········································
• 1.
• PLGA 미립구의 물리적 특성 ····················
• 2.
• PLGA 미립구의 형태학적 특성 ··················
• 3.
• in vitro release test ······························
• 4.
• in vivo release test ······························
• Ⅳ. 결 론 ··················································
• Ⅴ. 참고 문헌 ··············································