[보고서]나노 항암제류의 안전성 평가 기술 개발 연구

김상현

나노 항암제류의 안전성 평가 기술 개발 연구
Development of Safety Evaluation Protocol and Guideline for Nano-Anticancer Drugs 원문보기

보고서 정보
주관연구기관	경북대학교 산학협력단
연구책임자	김상현
참여연구자	이소영 , 최진경 , 김소연 , 강동우 , 이선혜 , 이연경 , 강원구 , 오태호 , 노금한 , 박진현 , 백상훈 , 백문창 , 문평곤 , 이정은 , 조영은 , 이민정
보고서유형	연차보고서
발행국가	대한민국
언어	한국어
발행년월	2013-10
과제시작연도	2013
주관부처	식품의약품안전평가원
사업 관리 기관	식품의약품안전처 Ministry of Food and Drug Safety
등록번호	TRKO201400011901
과제고유번호	1475007220
DB 구축일자	2014-07-26
키워드	나노,항암제,안전성,프로토콜,가이드라인Nano,anticancer drug,Safety,Protocol,Guideline

초록 ▼

○ 연구목표
나노항암제류의 안전성 평가 기술을 개발하기 위해 표준항암제인 독소루비신, 현재 상용화된 나노항암제, 상용화 가능성이 높은 카본 나노항암제 (CNT-DOX)를 대상으로 안전성 평가 (물리화학적 특성분석, in vitro/ in vivo 독성, 혈액독성, 독성동태) 및 시험 프로토콜을 작성하여 나노항암제류의안전성평가를위한 표준화된시험 프로토콜및 가이드라인을 마련함.
○ 연구내용
▷나노항암제류의 현황조사: 시장현황, 기술수준, 물질특성 및 상용화 가능성 분석
▷카본나노항암제 (CNT-DOX)의 제조 및 나노항암제류(Doxil 및 카본 나노항암제)의 물리화학적 특성 분석
- 카본나노튜브에 EDC링커를 이용하여항암제결합 및UV-vis분석을 이용한 결합확인
- 물리적 (Particle size analyzer, TEM), 화학적 (XPS, FTIR, Zeta Potential), 생물학적 분석
▷나노항암제의 in vitro/ in vivo 독성평가
- 각 장기를 대표할 세포주를 이용
- in vitro: 세포독성, 산화성 스트레스, 염증유발 및 미토콘드리아 기능평가
- in vivo: 일반독성(단회 및2주반복), 나노항암제 특이적 급성 과민반응
▷나노항암제의 혈액에 미치는 영향시험
- in vitro: Hemolysis, 적혈구 sedimentation & agglutination, 적혈구 Morphology, Prothrombintime (PT)/aPTT, 혈소판 응집
- in vivo : 나노항암제 처리 후 동물 혈액 내 마이크로파티클 분석 기초연구
- 동물혈액 내마이크로 파티클 분석 (독성에 대한 혈액 내 독성 마커)
▷나노항암제의 독성동태 시험
- 나노항암제의 조직분포 분석: 단회 및 반복 정맥 투여한 후 혈중 및 조직 (뇌, 간, 심장, 폐, 비장, 신장)에서Doxorubicin의 분포측정
- 나노항암제의 분포, 대사 및배설 분석: Doxorubicin의 활성 대사체인doxorubicinol을 측정하여 대사패턴 비교, 나노항암제의 용량변화에따른 혈중농도추이 및조직 분포를 simulation
- Computational modeling 기법을 이용하여Doxorubicin의 독성동태 자료 해석
▷나노항암제의 안전성 평가를 위한시험 프로토콜작성
○ 연구성과(응용분야 및 활용범위포함)
▷ 나노항암제 in vitro 독성 결과에 따르면 나노항암제의 독성기전은 항암제와 결합하고 있는 나노물질에 따라 완전히 다른 양상을 보임에 따라 그에 따른 나노항암제 특이적 안전성평가와 가이드라인에 활용 가능함
▷ 나노항암제의 in vivo 독성연구 결과에 따르면 나노항암제 안전성 평가 시 급성 과민반응에 대한 평가가 반드시 동반되어야 하고 항암제에 사용되는 나노물질의 표적장기에 대한 in vivo 독성 연구도 필요하다고 판단됨에 따라 나노항암제 특이적 안전성평가와 가이드라인에 활용 가능함
▷ 나노항암제의 종류에 따라 물리화학적 특성을 분석하여 독성을 유발하는 인자에 분석 실시
▷ 나노항암제가 혈액 내에서 일으킬 수 있는 기존의 독성 항목을 정리하였으며 microparticle을 이용한 새로운 독성 평가 항목을 마련함
▷ 나노항암제의 in vitro 및 in vivo 혈액 독성에 대한 화학적 및 분자생물학적 시험 프로토콜의 기반을 마련함
▷ 나노항암제의 분포, 대사 및 배설에 관한 정보를 얻고, 모델링/시뮬레이션을 통해 반복 투여 시 예상되는 약물 농도를 예측함
▷ 나노항암제의 표준 시험법의 자료로 활용함
▷ 의약품의 안전한 사용을 위한 체계적이고 과학적인 기반 마련
▷ 연구 수행과정을 통한 연구인력 양성

목차 Contents

표 지 ... 1
용역연구개발과제 연차실적․계획서 ... 2
제 출 문 ... 3
목 차 ... 4
당해연도 연구개발 실적 ... 6
1. 연구의 필요성 ... 6
2. 연구개발과제의 최종 연구목표와 당해연도 연구목표 ... 10
3. 연구개발과제의 당해연도 연구내용 및 방법 ... 12
4. 연구개발과제의 당해연도 연구결과 및 고찰 ... 56
5. 연구개발과제의 당해연도 연구성과 ... 374
6. 연구수행에 따른 문제점 및 대책 ... 384
7. 실적 요약문 ... 385
차기연도 연구과제 계획 ... 397
총괄연구개발과제 ... 398
1. 총괄요약문 ... 398
2. 총괄 차기연도 연구개발비 총괄표 ... 399
3. 총괄 차기연도 연구목표 및 내용 ... 403
4. 총괄 차기연도 연구개발 추진전략․방법 및 추진체계 ... 405
5. 총괄 차기연도 연구개발 결과의 활용방안 및 기대성과 ... 409
6. 총괄 주관연구책임자 인적사항 및 연구개발실적 ... 412
7. 총괄 참여연구원 편성표 ... 416
제(1)세부연구개발과제 ... 418
1.세부요약문 ... 419
2. 세부 차기연도 연구개발비 총괄표 ... 420
3. 세부 차기연도 연구목표 및 내용 ... 426
4. 세부 차기연도 연구개발 추진전략․방법 및 추진체계 ... 431
제(2)세부연구개발과제 ... 434
1. 세부요약문 ... 435
2. 세부 차기연도 연구개발비 총괄표 ... 436
3. 세부 차기연도 연구목표 및 내용 ... 441
4. 세부 차기연도 연구개발 추진전략․방법 및 추진체계 ... 447
5. 세부연구책임자 인적사항 및 연구개발실적 ... 449
제(3)세부연구개발과제 ... 453
1. 세부요약문 ... 454
2. 세부 차기연도 연구개발비 총괄표 ... 455
3. 세부 차기연도 연구목표 및 내용 ... 461
4. 세부 차기연도 연구개발 추진전략․방법 및 추진체계 ... 468
5. 세부연구책임자 인적사항 및 연구개발실적 ... 470
제(4)세부연구개발과제 ... 475
1. 세부요약문 ... 476
2. 세부 차기연도 연구개발비 총괄표 ... 477
3. 세부 차기연도 연구목표 및 내용 ... 483
4. 세부 차기연도 연구개발 추진전략․방법 및 추진체계 ... 487
5. 세부연구책임자 인적사항 및 연구개발실적 ... 488
끝페이지 ... 506

표/그림 (300)

표 i.v. 주입 후 카본 나노튜브가 130초 동안 circulation 발현되는 Dynamic contrast-enhanced imaging, 카본 나노물질의 혈액 소실율과 조직 내 축적도
표 카본 나노물질과 Doxorubicin 복합체의 Biodistribution에 의거한 장기별 독성 및 조직병리 분석
표 나노물질의 표면적 특성에 의한 면역/혈액 반응 활성화
표 나노물질의 혈액 적합성 및 혈청 단백질 활성화에 따른 혈액 응고
표 Doxorubicin
표 카본 나노물질 기반 항암제 (Doxorubicin-Carbon Nanomaterials)의 제조방법 및 물리화학적 분석
표 다중벽 탄소나노튜브의 표면을 카복실화 처리는 TEM으로 표면 결정구조의 defect가 형성된 것을 TEM으로 확인할 수 있고 FT-IR 분석을 통하여 표면이 성공적으로 카복실화된 것을 확인할수 있음. TGA를 통하여 카본 나노튜브 중량대비 카복실화가 약 30% 이상 됨을 관찰함
표 나노항암제의 물리화학적 분석
표 나노물질의 분석법 및 해석 방법
표 FDA에서 수행한 마이크로파티클 독성 연구
표 항암제 Doxorubicin의 화학구조와 Doxil 의단면도
표 카본 나노물질 기반 항암제 (Doxorubicin-Carbon Nanomaterials)의 제조방법 제시 및 물리화학적 분석
표 다중벽 탄소나노튜브의 표면을 카복실화 처리는 TEM 으로 표면 결정구조의 defect가 형성된 것을 TEM으로 확인할 수 있고 FT-IR 분석을 통하여 표면이 성공적으로 카복실화된 것을 확인할 수 있음. TGA를 통하여 카본 나노튜브 중량대비 카복실화가 약 30% 이상 됨을 관찰함
표 카본 나노항암제 명칭 및 약칭
표 나노물질의 분석법 및 해석 방법
표 카본 나노튜브 기반의 항암제에서 공유결합에 의하여 강력하게 결합되어 구조 변화가 유도됨
표 pH 및 효소 변화에 의한 약물방출. 공유결합을 극대화하여 약물지속시간을 대폭 증가시킴
표 FDA에서 수행한 마이크로파티클 독성 연구
표 급성 과민반응 시험 측정 사진
표 Effects of nano-anticancer drugs on MTT assay in Raw 264.7 cells. Cells were treated with drugs for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, ignificantly different from the control
표 Effects of Liposome on MTT assay in Raw 264.7 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of CNT on MTT assay in Raw 264.7 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of Dox on MTT assay in Raw 264.7 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effects of Doxil on MTT assay in Raw 264.7 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effects of Dox-CNT on MTT assay in Raw 264.7 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effects of nano-anticancer drugs in the apoptosis & necrosis of Raw 264.7. Cells were exposed to 0.5 μg/ml and analyzed by Annexin V-FITC/PI staining. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effect of nano-anticancer drugs on oxidative stress in Raw264.7 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to nano-anticancer drugs. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effect of Liposome on oxidative stress in Raw264.7 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to Liposome. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effect of CNT on oxidative stress in Raw264.7 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to CNT. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effect of Dox on oxidative stress in Raw264.7 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to Dox. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effect of Doxil on oxidative stress in Raw264.7 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to Doxil. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effect of Dox-CNT on oxidative stress in Raw264.7 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to Dox-CNT. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of nano-anticancer drugs in the mitochondrial potential of Raw 264.7 cells exposed to 0.5 μg/ml and analyzed by JC-1 staining. Data are shown as means ± SE (n =5). * p<0.05, significantly different from the control.
표 Effects of nano-anticancer drugs on nitric oxide(NO) production in Raw 264.7 cells. Raw 264.7 cells were treated with drugs for 24 hr. The level of NO production was expressed as the relative value of the untreated control group after 24hr exposure to nano-anticancer drugs. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of Liposome on NO production in Raw 264.7 cells. Raw 264.7 cells were treated with drug for 24 hr. The level of NO production was expressed as the relative value of the untreated control group after 24hr exposure to Liposome. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effects of CNT on NO production in Raw 264.7 cells. Raw 264.7 cells were treated with drug for 24 hr. The level of NO production was expressed as the relative value of the untreated control group after 24hr exposure to CNT. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of Dox on NO production in Raw 264.7 cells. Raw 264.7 cells were treated with drug for 24 hr. The level of NO production was expressed as the relative value of the untreated control group after 24hr exposure to Dox. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of Doxil on NO production in Raw 264.7 cells. Raw 264.7 cells were treated with drug for 24 hr. The level of NO production was expressed as the relative value of the untreated control group after 24hr exposure to Doxil. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Figure 5-E.was expressed as the relative value of the untreated control group after 24hr exposure to Dox-CNT. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effects of nano-anticancer drugs on TNF-α, IL-1β, IL-6 gene expression in Raw264.7 cells. Cells were treated with drugs for 24 hr. Real-time PCR amplification of the housekeeping gene, β-actin, was performed for each sample. Data are shown as means ± SE (n = 3). * p<0.05, significantly different from the control.
표 Effects of nano-anticancer drugs on MTT assay in HepG2 cells. Cells were treated with drugs for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effects of Liposome on MTT assay in HepG2 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of CNT on MTT assay in HepG2 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of Dox on MTT assay in HepG2 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effects of Doxil on MTT assay in HepG2 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effects of Dox-CNT on MTT assay in HepG2 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effects of nano-anticancer drugs in the apoptosis & necrosis of HepG2. Cells were exposed to 1 μg/ml and analyzed by Annexin V-FITC/PI staining. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effect of nano-anticancer drugs on oxidative stress in HepG2 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to nano-anticancer drugs. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effect of Liposome on oxidative stress in HepG2 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr me. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effect of CNT on oxidative stress in HepG2 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to CNT. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effect of Dox on oxidative stress in HepG2 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to Dox. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effect of Doxil on oxidative stress in HepG2 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to Doxil. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effect of Dox-CNT on oxidative stress in HepG2 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to Dox-CNT. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effects of nano-anticancer drugs in the mitochondrial potential of HepG2 cells exposed to 1 μg/ml and analyzed by JC-1 staining. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effects of nano-anticancer drugs on TNF-α, IL-1β, IL-6 gene expression in HepG2 cells. Cells were treated with drugs for 24 hr. Real-time PCR amplification of the housekeeping gene, β-actin, was performed for each sample. Data are shown as means ± SE (n = 3). * p<0.05, significantly different from the control.
표 Effects of nano-anticancer drugs on MTT assay in AML-2 cells. Cells were treated with drugs for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effects of Liposome on MTT assay in AML-2 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of CNT on MTT assay in AML-2 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of Dox on MTT assay in AML-2 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of Doxil on MTT assay in AML-2 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effects of Dox-CNT on MTT assay in AML-2 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of nano-anticancer drugs in the apoptosis & necrosis of AML-2 cells. Cells were exposed to 0.035 μg/ml and analyzed by Annexin V-FITC/PI staining. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effect of nano-anticancer drugs on oxidative stress in AML-2 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to nano-anticancer drugs. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effect of Liposome on oxidative stress in AML-2 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to Liposome. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effect of CNT on oxidative stress in AML-2 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to CNT. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effect of Dox on oxidative stress in AML-2 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to Dox. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effect of Doxil on oxidative stress in AML-2 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to Doxil. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effect of Dox-CNT on oxidative stress in AML-2 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to Dox-CNT. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of nano-anticancer drugs in the mitochondrial potential of AML-2 cells exposed to 0.035 μg/ml and analyzed by JC-1 staining. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of nano-anticancer drugs on TNF-α, IL-1β, IL-6 gene expression in AML-2 cells. Cells were treated with drugs for 24 hr. Real-time PCR amplification of the housekeeping gene, β-actin, was performed for each sample. Data are shown as means ± SE (n = 3). * p<0.05, significantly different from the control.
표 Effects of nano-anticancer drugs on MTT assay in SK-MES-1 cells. Cells were treated with drugs for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of Liposome on MTT assay in SK-MES-1 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of CNT on MTT assay in SK-MES-1 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of Dox on MTT assay in SK-MES-1 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effects of Doxil on MTT assay in SK-MES-1 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effects of Dox-CNT on MTT assay in SK-MES-1 cells. Cells were treated with drug for 24 hr. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of nano-anticancer drugs in the apoptosis & necrosis of SK-MES-1. Cells were exposed to 2 μg/ml and analyzed by Annexin V-FITC/PI staining. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effect of nano-anticancer drugs on oxidative stress in SK-MES-1 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to nano-anticancer drugs. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effect of Liposome on oxidative stress in SK-MES-1 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to Liposome. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effect of CNT on oxidative stress in SK-MES-1 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to CNT. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effect of Dox on oxidative stress in SK-MES-1 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to Dox. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effect of Doxil on oxidative stress in SK-MES-1 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to Doxil. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control
표 Effect of Dox-CNT on oxidative stress in SK-MES-1 cells. The level of ROS production was expressed as the relative value of the untreated control group after 24 hr exposure to Dox-CNT. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of nano-anticancer drugs in the mitochondrial potential of SK-MES-1 cells exposed to 2 μg/ml and analyzed by JC-1 staining. Data are shown as means ± SE (n = 5). * p<0.05, significantly different from the control.
표 Effects of nano-anticancer drugs on TNF-α, IL-1β, IL-6 gene expression in SK-MES-1 cells. Cells were treated with drugs for 24 hr. Real-time PCR amplification of the housekeeping gene, β-actin, was performed for each sample. Data are shown as means ± SE (n = 3). * p<0.05, significantly different from the control.
표 Body weight in male ICR mice for 14 days after single exposure. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of food consumption in male ICR mice for 14 days after single exposure. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of water consumption in male ICR mice for 14 days after single exposure. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of heart weight in single exposed male ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control
표 The change of Lung weight in single exposed male ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control
표 The change of liver weight in single exposed male ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of kidney weight in single exposed male ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of thymus weight in single exposed male ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of spleen weight in single exposed male ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of lymph node weight in single exposed male ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of brain weight in single exposed male ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 Red blood cell counts in single exposed male ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 White blood cell counts in single exposed male ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control
표 Body weight in female ICR mice for 14 days after single exposure. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of food consumption in female ICR mice for 14 days after single exposure. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of water consumption in female ICR mice for 14 days after single exposure. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of heart weight in single exposed female ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control
표 The change of Lung weight in single exposed female ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of liver weight in single exposed female ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of kidney weight in single exposed female ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of thymus weight in single exposed female ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of spleen weight in single exposed female ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of lymph node weight in single exposed female ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of brain weight in single exposed female ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 Red blood cell counts in single exposed female ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 White blood cell counts in single exposed female ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 Body weight in male ICR mice for 14 days after repeated exposure. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of food consumption in male ICR mice for 14 days after repeated exposure. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of water consumption in male ICR mice for 14 days after repeated exposure. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of heart weight in male ICR mice of repeated exposure for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of Lung weight in male ICR mice of repeated exposure for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of liver weight in male ICR mice of repeated exposure for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of kidney weight in male ICR mice of repeated exposure for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of thymus weight in male ICR mice of repeated exposure for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of spleen weight in male ICR mice of repeated exposure for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of lymph node weight in male ICR mice of repeated exposure for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The change of brain weight in male ICR mice of repeated exposure for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control
표 Red blood cell counts in male ICR mice of repeated exposure for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 White blood cell counts in male ICR mice of repeated exposure for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 The microscopic changes of heart in male ICR mice for 14 days after repeated exposure. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The organ sections were stained with hematoxylin and eosin. A: Control, B: Liposome, C: CNT, D: Dox, E: Doxil 5 mg/kg, F: Dox-CNT 5 mg/kg
표 The microscopic changes of lung in male ICR mice for 14 days after repeated exposure. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The organ sections were stained with hematoxylin and eosin. A: Control, B: Liposome, C: CNT, D: Dox, E: Doxil 5 mg/kg, F: Dox-CNT 5 mg/kg
표 The microscopic changes of liver in male ICR mice for 14 days after repeated exposure. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The organ sections were stained with hematoxylin and eosin. A: Control, B: Liposome, C: CNT, D: Dox, E: Doxil 5 mg/kg, F: Dox-CNT 5 mg/kg
표 The microscopic changes of kidney in male ICR mice for 14 days after repeated exposure. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The organ sections were stained with hematoxylin and eosin. A: Control, B: Liposome, C: CNT, D: Dox, E: Doxil 5 mg/kg, F: Dox-CNT 5 mg/kg
표 The microscopic changes of thymus in male ICR mice for 14 days after repeated exposure. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The organ sections were stained with hematoxylin and eosin. A: Control, B: Liposome, C: CNT, D: Dox, E: Doxil 5 mg/kg, F: Dox-CNT 5 mg/kg
표 The microscopic changes of spleen in male ICR mice for 14 days after repeated exposure. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The organ sections were stained with hematoxylin and eosin. A: Control, B: Liposome, C: CNT, D: Dox, E: Doxil 5 mg/kg, F: Dox-CNT 5 mg/kg
표 Systolic blood pressure in single exposed male mice. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 Heart rate in single exposed male mice. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control
표 Blood flow rate in single exposed male mice. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 Histamine of serum in single exposed male mice. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 Serum IgE levels in single exposed female ICR mice for 14 days. Mice were respectively administered by intravenous injection with liposome, CNT, Dox, Doxil (0.2, 1, 5 mg/kg) and Dox-CNT (0.2, 1, 5 mg/kg). The results are presented as mean ± SE (n = 10). * p < 0.05, significantly different from the control.
표 항암제 Doxorubicin의 화학구조와 Doxil의 단면도
표 나노항암제 개발 진행역사
표 독실 구조
표 ABRAXANE 구조
표 Cryo-TEM of DOXOVES®
표 Oxide maximization of CNT: Change of surface chemistry and weight.
표 Loading control of amide bonded Dox amount.
표 Raman analysis of CNT-Dox
표 Cryo-TEM images of CNT-Dox.
표 Size of various nanoparticles including mwCNT, Dox-CNT, Dox, Doxil and Liposome.
표 Quenching effect increased as strong amide bond is increased.
표 UV-vis analysis on CNT-Dox shows loading amount more than 30%.
표 Drug release of Dox-CNT by change of pH 및 enzymes
표 Intracellular trafficking and effectiveness of CNT-Dox compared to Dox and Doxil
표 Amount of delivered CNT-Dox to 1, 3, 4 sub-groups
표 Effects of CNT on mouse erythrocyte. Erythrocyte were treated with CNT (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 1hr. The results are presented as mean ± SE
표 Effects of CNT-DOX on mouse erythrocyte. Erythrocyte were treated with CNT-DOX (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 1hr. The results are presented as mean ± SE
표 Effects of Doxorubicin on mouse erythrocyte. Erythrocyte were treated with Doxorubicin (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 1hr. The results are presented as mean ± SE
표 Effects of Liposome on mouse erythrocyte. Erythrocyte were treated with Liposome (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 1hr. The results are presented as mean ± SE
표 Effects of Doxil on mouse erythrocyte. Erythrocyte were treated with Doxil (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 1hr. The results are presented as mean ± SE
표 Effects of CNT on human erythrocyte. Erythrocyte were treated with CNT (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 1hr. The results are presented as mean ± SE
표 Effects of CNT-DOX on human erythrocyte. Erythrocyte were treated with CNT-DOX (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 1hr. The results are presented as mean ± SE
표 Effects of Doxorubicin on human erythrocyte. Erythrocyte were treated with Doxorubicin (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 1hr. The results are presented as mean ± SE
표 Effects of Liposome on human erythrocyte. Erythrocyte were treated with Liposome (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 1hr. The results are presented as mean ± SE
표 Effects of Doxil on human erythrocyte. Erythrocyte were treated with Doxil (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 1hr. The results are presented as mean ± SE
표 Effects of CNT on mouse erythrocyte. Erythrocyte were treated with CNT (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 2hrs. The results are presented as mean ± SE
표 Effects of CNT-DOX on mouse erythrocyte. Erythrocyte were treated with CNT-DOX (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 2hrs. The results are presented as mean ± SE
표 Effects of DOX on mouse erythrocyte. Erythrocyte were treated with DOX (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 2hrs. The results are presented as mean ± SE
표 Effects of Liposome on mouse erythrocyte. Erythrocyte were treated with Liposome (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 2hrs. The results are presented as mean ± SE
표 Effects of Doxil on mouse erythrocyte. Erythrocyte were treated with Doxil (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 2h. The results are presented as mean ± SE
표 Control of mouse erythrocyte agglutination and sedimentation. Erythrocyte were treated with PBS for 2 h.
표 Effects of CNT on human erythrocyte. Erythrocyte were treated with CNT (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 2hrs. The results are presented as mean ± SE
표 Effects of CNT-DOX on human erythrocyte. Erythrocyte were treated with CNT-DOX (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 2hrs. The results are presented as mean ± SE
표 Effects of Doxorubicin on human erythrocyte. Erythrocyte were treated with Doxorubicin (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 2hrs. The results are presented as mean ± SE
표 Effects of Liposome on human erythrocyte. Erythrocyte were treated with Liposome (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 2hrs. The results are presented as mean ± SE
표 Effects of Doxil on human erythrocyte. Erythrocyte were treated with Doxil (55 ug/ml, 11 ug/ml, 2.2 ug/ml) for 2hrs. The results are presented as mean ± SE
표 Control of human erythrocyte agglutination and sedimentation. Erythrocyte were treated with PBS for 2hrs.
표 Control of mouse erythrocyte morphology observed under the TEM
표 Effects of CNT on mouse erythrocyte morphology observed under the TEM (transmission electron microscopy). Erythrocyte were treated with CNT (55 ug/ml) for 1hrs.
표 Effects of CNT-DOX on mouse erythrocyte morphology observed under the TEM (transmission electron microscopy). Erythrocyte were treated with CNT-DOX (55 ug/ml) for 1hrs.
표 Effects of DOX on mouse erythrocyte morphology observed under the TEM (transmission electron microscopy). Erythrocyte were treated with DOX (55 ug/ml) for 1hrs.
표 Effects of Liposome on mouse erythrocyte morphology observed under the TEM (transmission electron microscopy). Erythrocyte were treated with Liposome (55 ug/ml) for 1hrs.
표 Effects of Doxil on mouse erythrocyte morphology observed under the TEM (transmission electron microscopy). Erythrocyte were treated with Doxil (55 ug/ml) for 1hrs.
표 Effects of CNT on human erythrocyte morphology observed under the EM (electron microscopy). Erythrocyte were treated with CNT (55 ug/ml) for 1hrs
표 Effects of CNT-DOX on human erythrocyte morphology observed under the EM (electron microscopy). Erythrocyte were treated with CNT-DOX (55 ug/ml) for 1hrs.
표 Effects of CNT on human platelet coagulation. Plasma were treated with CNT (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as trace curve
표 Effects of CNT-DOX on human platelet coagulation. Plasma were treated with CNT-DOX (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as trace curve
표 Effects of Doxorubicin on human platelet coagulation. Plasma were treated with Doxorubicin (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as trace curve
표 Effects of Liposome on human platelet coagulation. Plasma were treated with Liposome (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as trace curve
표 Effects of Doxil on human platelet coagulation. Plasma were treated with Doxil (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as trace curve
표 Control of human platelet coagulation. Plasma were treated with collagen. The results are presented as trace curve
표 Effects of CNT on mouse aPTT (activated partial thromboplastin time). Plasma were treated with CNT (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of CNT-DOX on mouse aPTT (activated partial thromboplastin time). Plasma were treated with CNT-DOX (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of Doxorubicin on mouse aPTT (activated partial thromboplastin time). Plasma were treated with Doxorubicin (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of Liposome on mouse aPTT (activated partial thromboplastin time). Plasma were treated with Liposome (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of Doxil on mouse aPTT (activated partial thromboplastin time). Plasma were treated with Doxil (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of CNT on human aPTT (activated partial thromboplastin time). Plasma were treated with CNT (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of CNT-DOX on human aPTT (activated partial thromboplastin time). Plasma were treated with CNT-DOX (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of Doxorubicin on human aPTT (activated partial thromboplastin time). Plasma were treated with Doxorubicin (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of Liposome on human aPTT (activated partial thromboplastin time). Plasma were treated with Liposome (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of Doxil on human aPTT (activated partial thromboplastin time). Plasma were treated with Doxil (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of CNT on mouse PT(prothrombin time). Plasma were treated with CNT (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of CNT-DOX on mouse PT(prothrombin time). Plasma were treated with CNT-DOX (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of Doxorubicin on mouse PT(prothrombin time). Plasma were treated with Doxorubicin (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of Liposome on mouse PT(prothrombin time). Plasma were treated with Liposome (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of Doxil on mouse PT(prothrombin time). Plasma were treated with Doxil (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE (n = 3).
표 Effects of CNT on human PT(prothrombin time). Plasma were treated with CNT (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of CNT-DOX on human PT(prothrombin time). Plasma were treated with CNT-DOX (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of Doxorubicin on human PT(prothrombin time). Plasma were treated with Doxorubicin (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of Liposome on human PT(prothrombin time). Plasma were treated with Liposome (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Effects of Doxil on human PT(prothrombin time). Plasma were treated with Doxil (55 ug/ml, 11 ug/ml, 2.2 ug/ml,). The results are presented as mean ± SE
표 Comparative analysis of microparticle collection method. Microparicles were collected by Centrifugation(UC) and Exoquick(EQ). Collected microparticles were analyzed by Western blot(left) and Zeta-Potential(right). The results are almost similar between two methods
표 Effects of cisplatin on animal model. Mice were respectively administered by intravenous injection with cisplatin and microparticles were collected from mouse plasma using Exoquick. The results are presented as mean ± SE (n = 4). significantly different from the control.
표 Comparative analysis between total microparticles and AST activity in mouse blood. Mice were respectively administered by intravenous injection with cisplatin and microparticles were collected from mouse plasma using Exoquick. The results are almost similar between two methods.
표 Time courses of plasma doxorubicin concentrations following an intravenous injection of DOX 5 mg/kg in male and female ICR mice
표 Time courses of plasma doxorubicinol concentrations following an intravenous injection of DOX 5 mg/kg in male and female ICR mice
표 Time courses of plasma doxorubicin concentrations following an intravenous injection of Doxil® 0.2 mg/kg in male and female ICR mice
표 Time courses of plasma doxorubicin concentrations following an intravenous injection of Doxil® 1 mg/kg in male and female ICR mice
표 Time courses of plasma doxorubicin concentrations following an intravenous injection of Doxil® 5 mg/kg in male and female ICR mice
표 Time courses of plasma doxorubicinol concentrations following an intravenous injection of Doxil® 0.2 mg/kg in male and female ICR mice
표 Time courses of plasma doxorubicinol concentrations following an intravenous injection of Doxil® 1 mg/kg in male and female ICR mice
표 Time courses of plasma doxorubicinol concentrations following an intravenous injection of Doxil® 5 mg/kg in male and female ICR mice
표 Time courses of tissue doxorubicin amounts after an intravenous injection of DOX 5 mg/kg in male ICR mice
표 Time courses of tissue doxorubicin concentrations after an intravenous injection of DOX 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the kidney after an intravenous injection of DOX 5 mg/kg in male and female ICR mice
표 Time courses of doxorubicin amount in the liver after an intravenous injection of DOX 5 mg/kg in male and female ICR mice
표 Time courses of doxorubicin amount in the heart after an intravenous injection of DOX 5 mg/kg in male and female ICR mice
표 Time courses of doxorubicin amount in the lung after an intravenous injection of DOX 5 mg/kg in male and female ICR mice
표 Time courses of doxorubicin amount in the spleen after an intravenous injection of DOX 5 mg/kg in male and female ICR mice
표 Time courses of doxorubicin amount in the brain after an intravenous injection of DOX 5 mg/kg in male and female ICR mice
표 Time courses of doxorubicin amount in the testis after an intravenous injection of DOX 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the ovary after an intravenous injection of DOX 5 mg/kg in female ICR mice
표 Time courses of tissue doxorubicinol amounts after an intravenous injection of DOX 5 mg/kg in male ICR mice
표 Time courses of tissue doxorubicinol amounts after an intravenous injection of DOX 5 mg/kg in female ICR mice
표 Time courses of tissue doxorubicin amounts after an intravenous injection of Doxil® 5 mg/kg in male ICR mice
표 Time courses of tissue doxorubicin amounts after an intravenous injection of Doxil® 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the kidney after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the kidney after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the liver after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the liver after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the heart after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the heart after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the lung after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the lung after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the spleen after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the spleen after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the brain after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the brain after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the kidney after an intravenous injection of DOX or Doxil® 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the kidney after an intravenous injection of DOX or Doxil® 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the liver after an intravenous injection of DOX or Doxil® 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the liver after an intravenous injection of DOX or Doxil® 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the heart after an intravenous injection of DOX or Doxil® 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the heart after an intravenous injection of DOX or Doxil® 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the lung after an intravenous injection of DOX or Doxil® 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the lung after an intravenous injection of DOX or Doxil® 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the spleen after an intravenous injection of DOX or Doxil® 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the spleen after an intravenous injection of DOX or Doxil® 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the brain after an intravenous injection of DOX or Doxil® 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the brain after an intravenous injection of DOX or Doxil® 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the testis after an intravenous injection of DOX or Doxil® 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the ovary after an intravenous injection of DOX or Doxil® 5 mg/kg in female ICR mice
표 Time courses of tissue doxorubicinol amounts after an intravenous injection of Doxil® 5 mg/kg in male ICR mice
표 Time courses of tissue doxorubicinol amounts after an intravenous injection of Doxil® 5 mg/kg in female ICR mice
표 Time courses of doxorubicinol amount in the kidney after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in male ICR mice
표 Time courses of doxorubicinol amount in the kidney after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in female ICR mice
표 Time courses of doxorubicinol amount in the liver after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in male ICR mice
표 Time courses of doxorubicinol amount in the liver after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in female ICR mice
표 Time courses of doxorubicinol amount in the heart after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in male ICR mice
표 Time courses of doxorubicinol amount in the heart after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in female ICR mice
표 Time courses of doxorubicinol amount in the lung after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in male ICR mice
표 Time courses of doxorubicinol amount in the lung after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in female ICR mice
표 Time courses of doxorubicinol amount in the spleen after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in male ICR mice
표 Time courses of doxorubicinol amount in the spleen after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in female ICR mice
표 Time courses of doxorubicinol amount in the brain after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in male ICR mice
표 Time courses of doxorubicinol amount in the brain after an intravenous injection of Doxil® 0.2, 1 and 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the kidney after an intravenous injection of DOX or Doxil® 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the kidney after an intravenous injection of DOX or Doxil® 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the liver after an intravenous injection of DOX or Doxil® 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the liver after an intravenous injection of DOX or Doxil® 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the heart after an intravenous injection of DOX or Doxil® 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the heart after an intravenous injection of DOX or Doxil® 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the lung after an intravenous injection of DOX or Doxil® 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the lung after an intravenous injection of DOX or Doxil® 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the spleen after an intravenous injection of DOX or Doxil® 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the spleen after an intravenous injection of DOX or Doxil® 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the brain after an intravenous injection of DOX or Doxil® 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the brain after an intravenous injection of DOX or Doxil® 5 mg/kg in female ICR mice
표 Time courses of doxorubicin amount in the testis after an intravenous injection of DOX or Doxil® 5 mg/kg in male ICR mice
표 Time courses of doxorubicin amount in the ovary after an intravenous injection of DOX or Doxil® 5 mg/kg in female ICR mice
표 Correlation between population predicted and measured plasma concentrations in ICR mice after an intravenous injection of DOX. Solid line represents the line of identity
표 Correlation between individual predicted and measured plasma concentrations in ICR mice after an intravenous injection of DOX. Solid line represents the line of identity.
표 Diagnostic scatter plot for doxorubicin toxicokinetic model (DOX). Standardized residual versus time.
표 Diagnostic scatter plot for doxorubicin toxicokinetic model (DOX). Standardized residual versus model prediction.
표 Correlation between population predicted and measured plasma concentrations in ICR mice after an intravenous injection of Doxil®. Solid line represents the line of identity
표 Correlation between individual predicted and measured plasma concentrations in ICR mice after an intravenous injection of Doxil®. Solid line represents the line of identity
표 Diagnostic scatter plot for doxorubicin toxicokinetic model (Doxil®). Standardized residual versus time
표 Diagnostic scatter plot for doxorubicin toxicokinetic model (Doxil®). Standardized residual versus model prediction.
표 Predicted plasma concentration of doxorubicin after a repeated intravenous injection of 5 mg/kg DOX every 3 days for 2 weeks in ICR mice. Solid (black) and dashed (red) lines represent median and 90% confidence intervals of predicted doxorubicin concentrations, respectively.
표 Predicted plasma concentration of doxorubicin after a repeated intravenous injection of 5 mg/kg Doxil® every 3 days for 2 weeks in ICR mice. Solid (black) and dashed (red) lines represent median and 90% confidence intervals of predicted doxorubicin concentration, respectively.
표 나노항암제 공급을 통한 독성평가와 독성을 억제하는 물리화학적 지표 생성
표 독실에서의 약물 방출
표 다양한 항암제의 약물방출 비교분석
표 Nano-UPLC Q-TOF Premier
표 질량 분석기를 이용한 단백질 분석 과정

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나노 항암제류의 안전성 평가 기술 개발 연구
Development of Safety Evaluation Protocol and Guideline for Nano-Anticancer Drugs 원문보기

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나노 항암제류의 안전성 평가 기술 개발 연구 Development of Safety Evaluation Protocol and Guideline for Nano-Anticancer Drugs 원문보기

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나노 항암제류의 안전성 평가 기술 개발 연구
Development of Safety Evaluation Protocol and Guideline for Nano-Anticancer Drugs 원문보기

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