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Cellulose Acetate Butyrate의 작용기 비율에 따른 스텐트의 약물방출거동 및 물리화학적 특성과 그에 따른 세포 독성의 변화 관찰
장부남 ( Bunam Jang ),강성남 ( Sung Nam Kang ),금창헌 ( Chang Hun Kum ) 한국키틴키토산학회 2018 한국키틴키토산학회지 Vol.23 No.1
CAB 작용기 비율에 따라 스텐트의 약물 방출 거동 및 세포 독성 등의 차이를 관찰해 본 결과 표면적, 기계적 특성에서는 유사한 결과를 나타내었지만, 약물 방출 거동, 세포 독성 등과 같은 결과에서는 유의한 의미를 갖는 결과 값이 도출될 수 있었다. 특히 약물 방출 거동에서 CAB_B를 사용한 스텐트에 비해 CAB_A 사용 스텐트가 전반적으로 방출률이 저하되었고, 그에 따른 세포 독성이 저하되어 세포의 생존율이 증가됨을 관찰할 수 있었다. 본 연구를 통해 약물 방출 스텐트 필수 조건인 약물 방출 조절을 위한 CAB 고분자의 기능성을 살펴보았고, 그에 따른 세포 독성 실험을 통해 생체 적합성을 갖춘 고분자로서의 활용성과 스텐트 내 재협착 등의 부작용을 효과적으로 치료할 수 있는 잠재성 등을 평가할 수 있었다. Although drug eluting stent effectively reduce restenosis compared to bare metal stent, it still has the side effect of the drug, which are continuously caused after the interventional procedure of the coronary artery stent, such as delayed re-endothelialization and thrombosis induced by hypersensitivity of drug and inflammation. In order to solve this problem, a controlled drug release profile was able to induce re-endothelialization of vessel sufficiently by minimizing the side effect of drug. In this study, we investigated drug release behavior, physico-chemical characteristics and cytotoxicity of the stent prepared according to the ratio of butyrate functional group of cellulose acetate butyrate (CAB) in order to demonstrate the possibility of minimizing side effect of drug. CAB exhibits hydrophobic properties as the ratio of butyrate functional groups increases. The drug release rate of high butyrate group decreased about 1.5-3.8 times compared with low butyrate group in case of hydrophobic drug such as paclitaxel. The cytotoxicity was confirmed by the MTT assay. The cell viability in high butyrate group increased about 29% compared to low butyrate group. These results indicate drug release profile was able to controlled by the ratio of the butyrate functional group in CAB. In addition, it suggests that it can be used as a factor to minimize secondary adverse effects such as delayed reendothelialization and thrombosis through inhibition of hypersensitivity and toxicity induced by drug continuously.
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약물 방출 스텐트의 약물 방출 및 기계적 특성에 Ethylene Vinyl Alcohol와 Cellulose Acetate Butyrate가 미치는 영향
장부남 ( Bunam Jang ),강성남 ( Sung Nam Kang ),금창헌 ( Chang Hun Kum ) 한국키틴키토산학회 2017 한국키틴키토산학회지 Vol.22 No.1
Although drug-eluting stents have reduced the problem of restenosis, such stents exhibit side effects such as inhibition of re-endothelialization and inflammatory reactions due to persistent drug reactions and sensitivity of polymers. To solve this problem, suppressing the continuous drug reaction by controlling drug release behavior induce rapid vascular re-endothelization. In this study, we attempted to control drug release from a paclitaxel- and cilostazol-containing stent using ethylene vinyl alcohol (EVOH). We then used a scanning electron microscope and atomic force microscope to observe changes on the surface of the drug-releasing stent following the inclusion of EVOH in comparison with stent without EVOH. There were almost no differences on the surface of the drug-eluting stent due to EVOH. The drug release was initially higher in the EVOH-containing stent compared to the stent without EVOH, and the degradation behavior of the polymer not affected by addition of EVOH. Cytotoxicity of the stent containing EVOH was evaluated. EVOH did not exhibit any cytotoxicity due to the degree of controlled release of the drug. Additionally, mechanical property of stent was confirmed by using EVOH and cellulose acetate butyrate (CAB). Radial force increased in stent with EVOH compared to without EVOH although flexibility was not changed. These results suggest that the application of EVOH to drug-eluting stents does not affect the degradation behavior of the stent surface and polymer, but it could be expected to suppress the sustained and excessive response of the drug by rapid release of the drug.
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