저자는 연구를 가능하게하기위한 사우디 아라비아 투자 장학금 (I821)을 인정합니다. 저자는 크랜 필드 대학의 TEM 분석 전문가 지원을위한 박사 XIANWEI 리우에 감사하고 있습니다.

수 중유 에멀젼의 제조 (1) <ol><li> 글리세 릴 팔미 토 스테아 레이트 (120 mg)을, 이소 프로필 미리 스테이트 (60 mg)을, D-α 토코페롤 폴리에틸렌 글리콜 숙시 네이트 (30 mg) 및 대두 레시틴 (30 mg)을 계량하고 유기 용매에 12.5 ㎖ (6.25 mL의 아세톤 및 6.25에 추가 ml의 에탄올). 신속 수욕 (고체 지질의 녹는 점보다 5 ° C)의 온도 70 ℃에서, 혼합물을 용해. </li><li> 위와 같은 온도에서 가열 될 폴록 사머 188 솔루션의 1-3% (각각)를 달성하기 위해 DDH 2 O의 12.5 ㎖에 Poloxamer188 125, 250 또는 375 mg을 하나를 추가합니다. </li><li> 400 rpm으로 자기 교반하에 에멀젼을 형성하는 단계에서 1.1 적하 유상 용액을 단계 1.2에서 성상 용액을 추가한다. 또 다른 4 시간이 유기 용매의 증발을 허용하기 위해 400 rpm으로 교반 에멀젼. </li></ol> 2. 응고 및 균질화 <ol><li> t를 남겨2 시간이 /으로 결정화를 공고히 할 수있는 차가운 방 (4 ° C)에서 그는 유화. </li><li> NLC를 얻으려면 10 ~ 40 분 동안 10,000-15,000 rpm으로 균질 높은 투명한 분산 (HSD)에 에멀젼 대상으로 할 수 없다. </li></ol> NLC 준비 3. 최적화 <ol><li> 10000, 15000 및 20000 RPM의 속도로 1, 2, 3 % 확관 HSD의 계면 활성제 농도의 단계 2.2에서 샘플을 각각 10, 20, 30 및 40 분의 시간 간격으로 각각 </li><li> 입자 크기 (PS), 폴리 분산 지수 (PDI), 형태와 미세 구조 (20)에 대한 샘플을 검사합니다. 참고 : 최적으로 결정되는 가장 작은 크기 (155 ㎚) 및 PDI (0.2) 값을 갖는 입자를 생성 매개 변수를. </li></ol> DAC-로드 NLC 4. 준비 (NLC-DAC) <ol><li> 수조에서 70 ℃에서 상기 혼합물을 용해 전에 DAC (70 mg)을 첨가하여 단​​계 1.1에 기재된 바와 같이 유상 용액을 제조 하였다. </li><li> 피1 %의 계면 활성제와 단계 1.2에 기재된 바와 같이, 수성 상 용액을 repare, 400 rpm으로 자기 교반하에 에멀젼을 형성하는 단계에서 4.1 적하 그 제조 방법이 용액을 추가한다. 유기 용매를 증발 추가로 4 시간 동안 유화를 저어. </li><li> / 고화 단계 2에 기술 된 바와 같이 결정화, 마지막 3 단계에서 최적의 파라미터를 이용하여 높은 투명 분산액 (HSD)의 에멀젼을 환자에게 2 시간 동안 냉장실 (4 ℃)에서 에멀젼을 떠난다. </li></ol>

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저자는 공개 아무것도 없어.

지질 계 나노 입자는 소수성 약물 전달을위한 높은 친 유성 담체를 제공하는데 이용되어왔다. NLC 방 체온에서 고체 고체 지질 나노 캐리어 2 세대이다. 덜 완전한 결정화에서 NLC 결과 액체 지질로 고체 지질의 혼입, 따라서 약물 적재 효율을 증가시키고 저장 중에 캡슐화 된 약물의 제명을 감소시킨다. NLC 합성에 대해 가장 일반적으로 사용되는 방법은 수 중유 에멀젼, 균질화 및 응고 / 결정 (21, 22)을 포함한다. 저온에서 응고가 내 유상이 결정화 할 수 있도록하는 동안 균질화는 NLCS 수성 상에 충분히 분산시킬 수있다. 다른 균질화 방법은 이전 및 / 또는 고화 (23, 24) 동안 사용되는 자기 교반, 초음파 및 HSD 포함보고되었다 </s&gt;입니다. 이 연구에서, 일반적으로 사용되는 방법은 초기 NLC 제조 하였다. 결과는 만족스럽지 같이, 상기 방법은 HSD 응고 후에인가되도록 수정되었다. 같은 지질 (23, 25)를 사용하여 NLC 준비에 이전 보고서와 비교하여 NLC 합성 간단하면서이 수정, 입자 생성, PS 및 PDI 제어에 매우 효과적인 입증했다. 너무 길거나 너무 짧은 시간이 NLC의 생성에 부정적인 영향을 미칠 것 같이 증발 (프로토콜 1.3)과 응고 (프로토콜 2.1)의 길이가 매우 중요하다고 지적 가치가 있었다. 이 연구는 NLC 입자 및 응집이 응고하는 동안 형성된 것이 좋습니다. HSD 인해 NLCS 사이의 소수성 상호 작용을 가능하게했다 응집을 방해하고, 또한 철저하게 계면 활성제를 리믹스하여 입자를 안정화 할 수있다. 합성 과정은 t 최적화 된모자 NLC 및 NLC-DAC들은 크기가 155 ± 10 nm이고, 190 ± 10 nm의 각각 0.2 ± 0.01 PDI로 제조 하였다. 입자 크기와 작은 PDI 값이 균일의 높은 수준의 충분한 분산 에너지가 달성되었다 잘 입자의 응집체의 중단에 대한 솔루션 내에 분포되어 있음을 나타냅니다. 이 경향이없는 나노 100-200 입자는 0.5 이하의 PDI 동안, 따라서 생체 26,27 긴 혈액 순환 시간을 갖는, 단핵 식세포 시스템을 포함하는 비 - 표적 세포에 의해 통풍 관 제안 표시이다되었습니다 입자의 응집 (28); 입자 (29) 사이의 크기의 균일 성이 높을수록 PDI 값 하측. 또한 더 PS 감소 될 수있는 최적의 지점 위의 HSD 속도와 시간의 증가, 그리고 작은 입자뿐만 아니라 재 집계 사이의 상호 작용에 따라서 증가. NLC와 N 사이의 크기와 구조의 차이LC-DAC는 DAC 로딩 및 캡슐이 성공적으로 제안합니다. 액체 지질 매트릭스에서 릴리스 한 후 고체 지질 결정에서 다음에 외부 층에서 먼저 약물 방출을 포함 할 수 지질 행렬이 연장 된 약물 방출에 대한 가능성을 제공하는 내부의 아우터 NLC의 층과 캡슐화에 결합하는 약물, NLC 30. 현재 네 nanoformulations은 단일 에이전트로 DAC의 전달을 위해 시도되었다. 보고 최신 제제는 32 결투의 DAC의 캡슐화 및 비타민 위해 설계되었습니다. 그러나 이들 제제는 낮은 봉입 효율 및 / 또는 상대적으로 복잡한 합성 과정에서 겪었다. 이는 이전에보고 된 다른 캡슐화 유리한 증명 NLC와 DAC의 캡슐화에 대한 첫 번째 보고서입니다. NLC-DAC는 확인이 용이하고 높은 마약 캡슐화 및 약물 부하 효율 (20)을 제공한다. NLC-DAC는 거의 50 %를 보였다는 최대 30 시간 20 서서히 방출 남은 동안 제 2 시간 내에 출시 약물. 초기 릴리스는이 제제는 임상 현재 사용중인 제제를 대체 할 이상적인하지 않을 수도 있음을 나타내는, 상기 NLC의 표면에 계면 활성제 층과 약물의 결합으로 인해 수 있습니다. NLC-DAC의 약물은 이전에 (10)를보고 나노 에멀젼에 비해 더 안정적 등장하지만. 또한, 지질 기초하여 차량이 초기 약물 방출 잠재적 이어지지 것 인 본 연구에서 개발 된 NLC-DAC는 국소 도포를위한 잠재적으로 유용 할 수 있다는 것을 나타내는, 국소 약물 전달 32, 10을 통해 피부 흑색 종 및 표피 유사 암을 치료하는데 제안되었다 심한 전신 독성에. 대상에 대한 때문에 지금까지 개발 가능한 약물 전달 캐리어와 집단 제한, 추가 연구가 DAC 전달을위한 고급 나노 물질을 개발하는 데 필요한암 치료.

다카르 바진이 (DAC)는 세포주기의 정지 및 세포 사멸 한 선도 핵산 메틸화 또는 직접적인 DNA 손상으로 인한 항암 활성을 나타낸다 알킬화제이다. 제 선 화학 요법 제로서, DAC는 단독으로 또는 각종 암 치료 용 2-6 다른 항암제와 함께 사용되어왔다. 그것은 지금까지 피부암 -3,7,8-의 가장 적극적인 형태의 피부 및 전이성 흑색 종을 치료에 사용되는 가장 활성제이다. 반응률은, 그러나, 기껏해야 20 %이고, 치료 효과는 종종 심각한 전신성 부작용이 수반된다. 자연 형태에서, DAC는 친수성이며 인해 감광성 9 불안정합니다. 임상 사용을 위해 사용할 수있는 유일한 공식은 현재 정맥 주입 7,8를위한 서스펜션에 사용되는 멸균 분말이다. 낮은 응답 속도와 높은 전신 독성 연구약물 먹었다는 열악한 수용성에 크게 기인 약 10의 최대 투여 량을 제한하는 비 표적 부위에서 표적 부위에 따라서 낮은 가용성 높은 분포. 약제 내성의 발달과 함께 정맥 입장 후 분해성 대사 임상 응용 및 약물 (11)의 치료 효과를 제한한다. 따라서, 악성 흑색 종을 치료하기위한 대체 DAC 제형 개발이 절실히 요구되고있다. 등. 잠재적 인 약물 담체로서 12 나노 입자는 지난 10 년간 관심이 증가 받고있다 의한 약물 로딩을 증가시키는 능력에 Marilene 검토 리포좀을 함유하는 콜로이드 시스템은 미셀 또는 나노 입자를 집중 약물 투여에서의 사용을 위해 연구되었다 효율성, 제어 약물 방출, 약물 동태 및 생체 분포, 따라서 R을 향상약물 전신 독성 (13)를 끌어 내다. 몇 nanoformulations 그러나, 포토 변질 약물 증가 약물 용해도 보호 보여주는 원경 DAC 배달 조사 및 치료 효과 10,14,15 개선되었다. 그러나 일부는 비용 대비 효과가 없습니다 합성 고분자 나노 입자를 사용하는 동안 낮은 캡슐화 효율 고통이 제제. 고체 및 액체 지질의 혼합물로 이루어지는 나노 구조 지질 담체 (NLC)는 약물 전달을 위해 (16, 17)이 개발되었다. 캡슐화 할 수있는 약물은 높은 로딩의 결과 및 릴리스 (19)를 제어 종종 액체 고체 지질 지질 단계 (18)에서 모두 가용성이다. 본 연구는 글리세 릴 팔미 지질로서 이소 프로필 미리 스테이트를 사용 NLC 캡슐화에 기초하여 새로운 DAC 제제를 개발하는 것을 목표로하고있다. 제조 관련 중유 에멀젼, 증발, 응고 및 homogenizatio엔. 준비는 NLC 크기, 형태, 미세 구조 및 분산, 마약 캡슐화 효율 및 약물로드 (20)에 대해 특징으로하고있다.

<table><tbody><tr><td>Dacarbazine (DAC)</td><td>Sigma Aldrich (Gillingham Dorset, UK)</td><td>D2390-100MG</td><td>drug used for uploading</td></tr><tr><td>glyceryl palmitostearate&amp;nbsp;</td><td>Gattefoss&amp;eacute; (Saint_Priest_c&amp;eacute;dex, France)</td><td>85251-77-0</td><td>solid lipid&amp;nbsp;</td></tr><tr><td>d-&amp;alpha;- Tocopherol polyethylene glycol succinate (TPGS)</td><td>Sigma Aldrich (Gillingham Dorset, UK)</td><td>57668</td><td>lipid phase surfactant</td></tr><tr><td>Poloxamer 188</td><td>Sigma Aldrich (Gillingham Dorset, UK)</td><td>15759-1KG</td><td>liqiud phase surfactant</td></tr><tr><td>Acetone&amp;nbsp;</td><td>Sigma Aldrich (Gillingham Dorset, UK)</td><td>650501-1L</td><td>organic solvent</td></tr><tr><td>Ethanol&amp;nbsp;</td><td>Sigma Aldrich (Gillingham Dorset, UK)</td><td>459836-1L</td><td>organic solvent</td></tr><tr><td>Soybean lecithin (SL)</td><td>Cuisine Innovation (Dijon, France)</td><td>SLL1402</td><td>lipid phase surfactant</td></tr><tr><td>Double-distilled water was collected in our laboratory from</td><td>Millipore-Q Gradient A10 ultra-pure water system (Millipore, France)</td><td>SAS - 67120&amp;nbsp;</td><td>aqueous phase&amp;nbsp;</td></tr><tr><td>T 25 digital ULTRA-TURRAX</td><td>IKA</td><td>3725000</td><td>as high shear disperser</td></tr><tr><td>Hotplate Magnetic Stirrer</td><td>Scientific Support, Inc</td><td>1454&amp;nbsp;</td><td>emulsion homogenization</td></tr></tbody></table>

encapsulation of cancer therapeutic agent dacarbazine using nanostructured lipid carrier

임상 사용 다카 바진 (DAC)의 단 화학식 인해 수용액 중의 약물의 낮은 분산으로 불량한 치료 프로필을 제시 정맥 주입된다. 이것을 극복하기 위해, 글리세 릴 팔미 토 스테아 레이트 및 이소 프로필 미리 스테이트 이루어진 나노 지질 담체 (NLC)는 DAC를 캡슐화하기 위해 개발되었다. 제어 된 크기 NLCS은 수 중유 에멀젼의 응고 아래의 고전 단 분산 (HSD)를 사용하여 달성 하였다. 계면 활성제의 농도, 속도 및 HSD의 시간을 포함하는 합성 파라미터를 각각 MV, 크기, 분산액 (Polydispersion) 인덱스, 155 ± 10 nm의 제타 전위를 가진 작은 NLC을 달성하기 위해, 0.2 ± 0.01, 및 -43.4 ± 2 최적화 하였다. 최적의 매개 변수는 DAC로드 NLC 제조에 사용 하였다. DAC 탑재 생성 된 NLC는 각각, 크기, 분산액 (Polydispersion) 지수 190 ± 10 nm 인 제타 전위, 0.2 ± 0.01, 및 -43.5 ± 1.2 MV를 소유. 약물 봉입 EFFICIENCY 및 약물 부하는 각각 98 %와 14 %에 달했다. 이는 DAC가 NLC의 치료 적 프로파일을 향상시키기 위해 약물 캐리어로서의 새로운 잠재 후보가 될 수 있다는 의미 NLC DAC를 사용하여 캡슐화의 제 보고서이다.

다른 매개 변수와 함께 글리세 릴 팔미 이소 프로필 미리 스테이트를 사용하여 NLC와 NLC-DAC의 준비는 PS, PDI, 형태와 미세 구조 (20)를 위해 특성화되었다. NLCS의 PS와 PDI는 계면 활성제 농도, HSD 속도와 지속 시간에 의존했다. PS와 NLCS의 PDI에 의해 판단 된 바와 같이, 최적의 결과는 1 %의 계면 활성제, 따라서 wwew NLC에 대한 최적의 파라미터로서 선택된 30 분 (도 1A, B 및 C)에서 15,000 rpm으로 얇은 분산 속도를 달성했다 이 연구에서 준비. <img alt="그림 1" src="/files/ftp_upload/53760/53760fig1.jpg" /> NLC 제조에 사용되는 파라미터의 최적화는도 1. HSD의 최적의 계면 활성제의 농도 및 속도와 시간은 PS 및 PDI에 미치는 영향에 따라 결정 하였다. ( <strong&gt; A) PS에 계면 활성제 농도에 미치는 영향; HSD 속도와 PS에 시간 (B) 효과; PDI에 HSD 속도와 시간 (C) 효과. 이 그림은 20에서 수정되었습니다. 3 ± 표준 편차를 복제의 데이터는 같은 평균값을 제시 (평균 ± SD). 최적 파라미터 NLC-DAC의 제조에 사용 하였다. 달성 가장 작은 크기는 좋은 균일 성을 나타내는 0.2 ± 0.001의 PDI와 함께 모두 NLC (그림 2A) 150 ± 10 nm의 NLC-DAC (그림 2B) 190 ± 10 nm였다. <img alt="그림 2" src="/files/ftp_upload/53760/53760fig2.jpg" /> NLC의 그림 2. DLS 측정 (A) 일반 NLC의 최적 크기 분포.; (B) NLC-DAC의 최적 크기 분포. (그림 3) 구형을 보였다. <img alt="그림 3" src="/files/ftp_upload/53760/53760fig3.jpg" /> NLC와 NLC-DAC. NLC 모두와 NLC-DAC 그림 3. TEM 영상은 구형을 보였다. (A) 기본 NLC 구조는 활성제 층 (검은 색 화살표), 액체 지방 행렬 (백색 고체 화살표) 및 고체 지질 결정 (점선 흰색 화살표)를 포함하고; NLC에서 볼 수 있지만, 계면 층, 액체 지방 행렬 고체 지질 결정 팽창 등장 (B) NLC-DAC는 기본 구조를 나타낸다; 별도의 하부 구조는 약물로드를 나타내는 (점선 검정색 화살표로 나타낸) 고체 지질 결정 내부에 볼 수있다. 바 규모 : 50 nm의, 배율 : 55,000X. 이 그림은 20에서 수정되었습니다. NLC-DAC가 큰 크기를 도시도 2 및도 3에서 보이고 NLC에 비해 내부 구조 변경으로 &quot;1&quot;&gt;에서 NLC DAC의 업로드 및 캡슐화 크기와 구조의 변화에 의해 표시된다. NLC의 기본 구조는 활성제 층, 액체 지방 지질 매트릭스 고체 결정 (도 3a)를 포함한다. NLC-DAC는 함께 약물 충전 및 밀봉을 나타내는 고체 지질 결정 (도 3b) 안에 별도의 하부 구조와 더불어, NLC 것에 따라 팽창 계면 층, 액체 지방 행렬 고체 지질 크리스탈 기본 구조를 나타낸다. NLC 볼 고체 지질 결정 고체 지질 NLC-DAC 덜 결정화 것을 나타내는 NLC-DAC에 비해 밀도가 나타났다. 약물 봉입 효율 (EF) 및 약물 로딩 (DL) 비율은 다음의 방정식으로부터 유도 하였다 : &quot;fo를하기 : 유지-together.within 페이지를 =&quot;1 &quot;&gt; EE (%) = W 1 - W 1 / 2 × 100 = 98.5 % W 하향 링크 (%) = W 1 - W 2 / W 3 × 100 = 14 % 지질의 3 양 (20)을 추가 W 곳 DAC의 W (1) 양이, 미 포획 된 DAC의 2 량 (W)의 NLC에 추가.

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Encapsulation of Cancer Therapeutic Agent Dacarbazine Using Nanostructured Lipid Carrier

나노 지질 담체 (NLC)의 합성을위한 가장 보편적으로 사용되는 방법은 수 중유 에멀젼, 균질화 및 응고를 포함한다. 이것은 다카르 바진 전달을위한 잠재적 인 담체로서 바람직한 크기, 향상된 약물 봉입 약물 적재 효율이 NLC을 달성하기 위해, 응고 후의 고 전단 분산함으로써 여기 개질 하였다.

나노 구조 지질 캐리어를 사용하여 암 치료제 다카 바진의 캡슐화

The only formula of dacarbazine (Dac) in clinical use is intravenous infusion, presenting a poor therapeutic profile due to the low dispersity of the drug ...

encapsulation-cancer-therapeutic-agent-dacarbazine-using

Nanyang Technological University

Research

JoVE Journal

Chemistry

11.0K 조회수.  Cranfield University.  나노 지질 담체 (NLC)의 합성을위한 가장 보편적으로 사용되는 방법은 수 중유 에멀젼, 균질화 및 응고를 포함한다. 이것은 다카르 바진 전달을위한 잠재적 인 담체로서 바람직한 크기, 향상된 약물 봉입 약물 적재 효율이 NLC을 달성하기 위해, 응고 후의 고 전단 분산함으로써 여기 개질 하였다. 

비디오: Encapsulation of Cancer Therapeutic Agent Dacarbazine Using Nanostructured Lipid Carrier

A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles

Nanomedicine is an emerging form of therapy that harnesses the unique properties of particles that are nanometers in scale for biomedical application. Improving drug delivery to maximize therapeutic outcomes and to reduce drug-associated side effects are some of the cornerstones of present-day nanomedicine. Nanoparticles in particular have found a wide application in cancer treatment. Nanoparticles that offer a high degree of flexibility in design, application, and production based on the tumor microenvironment are projected to be more effective with rapid translation into clinical practice. The polymeric micellar nano-carrier is a popular choice for drug delivery applications.
In this article, we describe a simple and effective protocol for synthesizing drug-loaded, disulfide cross-linked micelles based on the self-assembly of a well-defined amphiphilic linear-dendritic copolymer (telodendrimer, TD). TD is composed of polyethylene glycol (PEG) as the hydrophilic segment and a thiolated cholic acid cluster as the core-forming hydrophobic moiety attached stepwise to an amine-terminated PEG using solution-based peptide chemistry. Chemotherapy drugs, such as paclitaxel (PTX), can be loaded using a standard solvent evaporation method. The O2-mediated oxidation was previously utilized to form intra-micellar disulfide cross-links from free thiol groups on the TDs. However, the reaction was slow and not feasible for large-scale production. Recently, an H2O2-mediated oxidation method was explored as a more feasible and efficient approach, and it was 96 times faster than the previously reported method. Using this approach, 50 g of PTX-loaded, disulfide cross-linked nanoparticles have been successfully produced with narrow particle size distribution and high drug loading efficiency. The stability of the resulting micelle solution is analyzed using disrupting conditions such as co-incubation with a detergent, sodium dodecyl sulfate, with or without a reducing agent. The drug-loaded, disulfide cross-linked micelles demonstrated less hemolytic activity when compared to their non-cross-linked counterparts.

To deliver cancer drugs to tumor sites with high specificity and reduced side effects, new methods based on nanoparticles are required. Here, we describe disulfide cross-linked micelles that can be easily prepared by hydrogen peroxide-mediated oxidation and are able to dissociate efficiently under a reducing tumor environment to release payloads.

가역 디설파이드 가교 미셀 제조를위한 손쉬운 효율적인 접근법

Nanomedicine is an emerging form of therapy that harnesses the unique properties of particles that are nanometers in scale for biomedical application. ...

연구

생화학

Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles

Amphiphilic block copolymers like polyethyleneglycol-block-polylactic acid (PEG-b-PLA) can self-assemble into micelles above their critical micellar concentration forming hydrophobic cores surrounded by hydrophilic shells in aqueous environments. The core of these micelles can be utilized to load hydrophobic, poorly water soluble drugs like docetaxel (DTX) and everolimus (EVR). Systematic characterization of the micelle structure and drug loading capabilities are important before in vitro and in vivo studies can be conducted. The goal of the protocol described herein is to provide the necessary characterization steps to achieve standardized micellar products. DTX and EVR have intrinsic solubilities of 1.9 and 9.6 &#181;g/ml respectively Preparation of these micelles can be achieved through solvent casting which increases the aqueous solubility of DTX and EVR to 1.86 and 1.85 mg/ml, respectively. Drug stability in micelles evaluated at room temperature over 48 hr indicates that 97% or more of the drugs are retained in solution. Micelle size was assessed using dynamic light scattering and indicated that the size of these micelles was below 50 nm and depended on the molecular weight of the polymer. Drug release from the micelles was assessed using dialysis under sink conditions at pH 7.4 at 37 oC over 48 hr. Curve fitting results indicate that drug release is driven by a first order process indicating that it is diffusion driven.

The goal of this protocol is to describe the preparation and characterization of physically entrapped, poorly water soluble drugs in micellar drug delivery systems composed of amphiphilic block copolymers.

준비 및 개인의 특성과 다중 약물은 물리적으로 고분자 미셀을 포획로드

Amphiphilic block copolymers like polyethyleneglycol-block-polylactic acid (PEG-b-PLA) can self-assemble into micelles above their critical micellar ...

화학

Facile Preparation of Internally Self-assembled Lipid Particles Stabilized by Carbon Nanotubes

We present a facile method to prepare nanostructured lipid particles stabilized by carbon nanotubes (CNTs). Single-walled (pristine) and multi-walled (functionalized) CNTs are used as stabilizers to produce Pickering type oil-in-water (O/W) emulsions. Lipids namely, Dimodan U and Phytantriol are used as emulsifiers, which in excess water self-assemble into the bicontinuous cubic Pn3m phase. This highly viscous phase is fragmented into smaller particles using a probe ultrasonicator in presence of conventional surfactant stabilizers or CNTs as done here. Initially, the CNTs (powder form) are dispersed in water followed by further ultrasonication with the molten lipid to form the final emulsion. During this process the CNTs get coated with lipid molecules, which in turn are presumed to surround the lipid droplets to form a particulate emulsion that is stable for months. The average size of CNT-stabilized nanostructured lipid particles is in the submicron range, which compares well with the particles stabilized using conventional surfactants. Small angle X-ray scattering data confirms the retention of the original Pn3m cubic phase in the CNT-stabilized lipid dispersions as compared to the pure lipid phase (bulk state). Blue shift and lowering of the intensities in characteristic G and G&#39; bands of CNTs observed in Raman spectroscopy characterize the interaction between CNT surface and lipid molecules. These results suggest that the interactions between the CNTs and lipids are responsible for their mutual stabilization in aqueous solutions. As the concentrations of CNTs employed for stabilization are very low and lipid molecules are able to functionalize the CNTs, the toxicity of CNTs is expected to be insignificant while their biocompatibility is greatly enhanced. Hence the present approach finds a great potential in various biomedical applications, for instance, for developing hybrid nanocarrier systems for the delivery of multiple functional molecules as in combination therapy or polytherapy.

We report on a smart application of carbon nanotubes for kinetic stabilization of lipid particles that contain self-assembled nanostructures in their cores. The preparation of lipid particles requires rather low concentrations of carbon nanotubes permitting their use in biomedical applications such as drug delivery.

탄소 나노 튜브에 의해 안정화 내부 자기 조립 된 지질 입자의 용이 한 제조

We present a facile method to prepare nanostructured lipid particles stabilized by carbon nanotubes (CNTs). Single-walled (pristine) and multi-walled ...

Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles

Micelles have been successfully used for the delivery of anticancer drugs. Amphiphilic polymers form core-shell structured micelles in an aqueous environment through self-assembly. The hydrophobic core of micelles functions as a drug reservoir and encapsulates hydrophobic drugs. The hydrophilic shell prevents the aggregation of micelles and also prolongs their systemic circulation in vivo. In this protocol, we describe a method to synthesize a doxorubicin lipophilic pro-drug, doxorubicin-palmitic acid (DOX-PA), which will enhance drug loading into micelles. A pH-sensitive hydrazone linker was used to conjugate doxorubicin with the lipid, which facilitates the release of free doxorubicin inside cancer cells. Synthesized DOX-PA was purified with a silica gel column using dichloromethane/methanol as the eluent. Purified DOX-PA was analyzed with thin layer chromatography (TLC) and 1H-Nuclear Magnetic Resonance Spectroscopy (1H-NMR). A film dispersion method was used to prepare DOX-PA loaded DSPE-PEG micelles. In addition, several methods for characterizing micelle formulations are described, including determination of DOX-PA concentration and encapsulation efficiency, measurement of particle size and distribution, and assessment of in vitro anticancer activities. This protocol provides useful information regarding the preparation and characterization of drug-loaded micelles and thus will facilitate the research and development of novel micelle-based cancer nanomedicines.

A protocol for the preparation and characterization of lipophilic doxorubicin pro-drug loaded 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG) micelles is described.

친 유성 독소루비신 전구 약물 미셀의 제조 및 특성화

Micelles have been successfully used for the delivery of anticancer drugs. Amphiphilic polymers form core-shell structured micelles in an aqueous ...

생체공학

Phase Change Dimethyldioctadecylammonium-Shelled Microdroplets as a Promising Drug Delivery System: Results on 3D Spheroids of Mammalian Tumor Cells

Significant improvement of phase-change perfluorocarbon microdroplets (MDs) in the vast theranostic scenario passes through the optimization of the MDs composition with respect to synthesis efficiency, stability, and drug delivery capability. To this aim, decafluoropentane (DFP) MDs stabilized by a shell of dimethyldioctadecylammonium bromide (DDAB) cationic surfactant were designed. A high concentration of DDAB-MDs was readily obtained within a few seconds by pulsed high-power insonation, resulting in low polydisperse 1 &#181;m size droplets. Highly positive &#950;-potential, together with a long, saturated hydrocarbon chains of the DDAB shell, are key factors to stabilize the droplet and the drug cargo therein. The high affinity of the DDAB shell with cell plasma membrane allows for localized chemotherapeutics delivery by increasing the drug concentration at the tumor cell interface and boosting the uptake. This would turn DDAB-MDs into a relevant drug delivery tool exhibiting high antitumor activity at very low drug doses.
In this work, the efficacy of such an approach is shown to dramatically improve the effect of doxorubicin against 3D spheroids of mammalian tumor cells, MDA-MB-231. The use of&#160;three-dimensional (3D) cell cultures developed in the form of multicellular tumor spheroids (i.e., densely packed cells in a spherical shape) has numerous advantages compared to 2D cell cultures: in addition to have the potential to bridge the gap between conventional in vitro studies and animal testing, it will improve the ability to perform more predictive in vitro screening assays for preclinical drug development or evaluate the potential of off-label drugs and new co-targeting strategies.

Decafluoropentane microdroplets developed with a shell of dimethyldioctadecylammonium bromide exhibited an exceptional colloidal stability and an actractive biointerface. DDAB-MDs proved to be efficient drug reservoirs characterized by a high affinity to plasma membranes together with enhanced uptake and antitumor activity of Doxorubicin against human triple-negative breast cancer (MDA-MB-231) 3D model.

Significant improvement of phase-change perfluorocarbon microdroplets (MDs) in the vast theranostic scenario passes through the optimization of the MDs ...

Targeted Plasma Membrane Delivery of a Hydrophobic Cargo Encapsulated in a Liquid Crystal Nanoparticle Carrier

The controlled delivery of drug/imaging agents to cells is critical for the development of therapeutics and for the study of cellular signaling processes. Recently, nanoparticles (NPs) have shown significant promise in the development of such delivery systems. Here, a liquid crystal NP (LCNP)-based delivery system has been employed for the controlled delivery of a water-insoluble dye, 3,3&#8242;-dioctadecyloxacarbocyanine perchlorate (DiO), from within the NP core to the hydrophobic region of a plasma membrane bilayer. During the synthesis of the NPs, the dye was efficiently incorporated into the hydrophobic LCNP core, as confirmed by multiple spectroscopic analyses. Conjugation of a PEGylated cholesterol derivative to the NP surface (DiO-LCNP-PEG-Chol) enabled the binding of the dye-loaded NPs to the plasma membrane in HEK 293T/17 cells. Time-resolved laser scanning confocal microscopy and F&#246;rster resonance energy transfer (FRET) imaging confirmed the passive efflux of DiO from the LCNP core and its insertion into the plasma membrane bilayer. Finally, the delivery of DiO as a LCNP-PEG-Chol attenuated the cytotoxicity of DiO; the NP form of DiO exhibited ~30-40% less toxicity compared to DiOfree delivered from bulk solution. This approach demonstrates the utility of the LCNP platform as an efficient modality for the membrane-specific delivery and modulation of hydrophobic molecular cargos.

A liquid crystal nanoparticle (LCNP) nanocarrier is exploited as a vehicle for the controlled delivery of a hydrophobic cargo to the plasma membrane of living cells.

액정 나노 입자 캐리어의 소수성화물 캡슐화의 대상 플라즈마 멤브레인 배달

The controlled delivery of drug/imaging agents to cells is critical for the development of therapeutics and for the study of cellular signaling processes. ...

Formulation and Characterization of Bioactive Agent Containing Nanodisks

The term nanodisk refers to a discrete type of nanoparticle comprised of a bilayer forming lipid, a scaffold protein, and an integrated bioactive agent. Nanodisks are organized as a disk-shaped lipid bilayer whose perimeter is circumscribed by the scaffold protein, usually a member of the exchangeable apolipoprotein family. Numerous hydrophobic bioactive agents have been efficiently solubilized in nanodisks by their integration into the hydrophobic milieu of the particle&#39;s lipid bilayer, yielding a largely homogenous population of particles in the range of 10-20 nm in diameter. The formulation of nanodisks requires a precise ratio of individual components, an appropriate sequential addition of each component, followed by bath sonication of the formulation mixture. The amphipathic scaffold protein spontaneously contacts and reorganizes the dispersed bilayer forming lipid/bioactive agent mixture to form a discrete, homogeneous population of nanodisk&#160;particles. During this process, the reaction mixture transitions from an opaque, turbid appearance to a clarified sample that, when fully optimized, yields no precipitate upon centrifugation. Characterization studies involve the determination of bioactive agent solubilization efficiency, electron microscopy, gel filtration chromatography, ultraviolet visible (UV/Vis) absorbance spectroscopy, and/or fluorescence spectroscopy. This is normally followed by an investigation of biological activity using cultured cells or mice. In the case of nanodisks harboring an antibiotic (i.e., the macrolide polyene antibiotic amphotericin B), their ability to inhibit the growth of yeast or fungi as a function of concentration or time can be measured. The relative ease of formulation, versatility with respect to component parts, nanoscale particle size, inherent stability, and aqueous solubility permits myriad in vitro and in vivo applications of nanodisk technology. In the present article, we describe a general methodology to formulate and characterize nanodisks containing amphotericin&#160;B as the hydrophobic bioactive agent.

Here, we describe the production and characterization of bioactive agents containing nanodisks. Amphotericin B nanodisks are taken as an example to describe the protocol in a stepwise manner.

나노디스크를 함유하는 생리활성제의 제형 및 특성화

The term nanodisk refers to a discrete type of nanoparticle comprised of a bilayer forming lipid, a scaffold protein, and an integrated bioactive agent. ...

Uptake of New Lipid-coated Nanoparticles Containing Falcarindiol by Human Mesenchymal Stem Cells

Nanoparticles are the focus of an increased interest in drug delivery systems for cancer therapy. Lipid-coated nanoparticles are inspired in structure and size by low-density lipoproteins (LDLs) because cancer cells have an increased need for cholesterol to proliferate, and this has been exploited as a mechanism for delivering anticancer drugs to cancer cells. Moreover, depending on drug chemistry, encapsulating the drug can be advantageous to avoid degradation of the drug during circulation in vivo. Therefore, in this&#160;study, this design is used to fabricate lipid-coated nanoparticles of the anticancer drug falcarindiol, providing a potential new delivery system of falcarindiol in order to stabilize its chemical structure against degradation and improve its uptake by tumors. Falcarindiol nanoparticles, with a phospholipid and cholesterol monolayer encapsulating the purified drug core of the particle, were designed. The lipid monolayer coating consists of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol (Chol), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE PEG 2000) along with the fluorescent label DiI (molar ratios of 43:50:5:2). The nanoparticles are fabricated using the rapid injection method, which is a fast and simple technique to precipitate nanoparticles by good-solvent for anti-solvent exchange. It consists of a rapid injection of an ethanol solution containing the nanoparticle components into an aqueous phase. The size of the fluorescent nanoparticles is measured using dynamic light scattering (DLS) at 74.1 &#177; 6.7 nm. The uptake of the nanoparticles is tested in human mesenchymal stem cells (hMSCs) and imaged using fluorescence and confocal microscopy. The uptake of the nanoparticles is observed in hMSCs, suggesting the potential for such a stable drug delivery system for falcarindiol.

This article describes the encapsulation of falcarindiol in lipid-coated 74 nm nanoparticles. The cellular uptake of the nanoparticles&#160;by human stem cells into lipid droplets is monitored by fluorescent and confocal imaging. Nanoparticles are fabricated by the rapid injection method of solvent shifting, and their size is measured with the dynamic light scattering technique.

Falcarindiol 인간 중간 엽 줄기 세포에 의해 포함 된 새로운 지질 코팅 나노 입자의

Nanoparticles are the focus of an increased interest in drug delivery systems for cancer therapy. Lipid-coated nanoparticles are inspired in structure and ...

Preparation and Characterization of Nanoliposomes for the Entrapment of Bioactive Hydrophilic Globular Proteins

Liposome nanocapsules have been applied for many purposes in the pharmaceutical, cosmetic, and food industries. Attributes of liposomes include their biocompatibility, biodegradability, non-immunogenicity, non-toxicity, and ability to entrap both hydrophilic and hydrophobic compounds. The classical hydration of thin lipid films in an organic solvent is applied herein as a technique to encapsulate tarin, a plant lectin, in nanoliposomes. Nanoliposome size, stability, entrapment efficiency, and morphological characterization are described in detail. The nanoliposomes are prepared using 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine (DOPE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (ammonium salt; DSPE-MPEG 2000), and cholesterylhemisuccinate (CHEMS) as the main constituents. Lipids are first dissolved in chloroform to obtain a thin lipid film that is subsequently rehydrated in ammonium sulfate solution containing the protein to be entrapped and incubated overnight. Then, sonication and extrusion techniques are applied to generate nanosized unilamellar vesicles. The size and polydispersity index of the nanovesicles are determined by dynamic light scattering, while nanovesicle morphology is assessed by scanning electron microscopy. Entrapment efficiency is determined by the ratio of the amount of unencapsulated protein to original amount of initially loaded protein. Homogeneous liposomes are obtained with an average size of 155 nm and polydispersity index value of 0.168. A high entrapment efficiency of 83% is achieved.

This study describes classical hydration using the thin lipid film method for nanoliposome preparation followed by nanoparticle characterization. A 47 kDa-hydrophilic and globular protein, tarin, is successfully encapsulated as a strategy to improve stability, avoid fast clearance, and promote controlled release. The method can be adapted to hydrophobic molecules encapsulation.

생리 활성 친수성 구형 단백질의 함정에 대한 나노 리포좀의 준비 및 특성화

Liposome nanocapsules have been applied for many purposes in the pharmaceutical, cosmetic, and food industries. Attributes of liposomes include their ...

Using In Vitro Live-cell Imaging to Explore Chemotherapeutics Delivered by Lipid-based Nanoparticles

Conventional imaging techniques can provide detailed information about cellular processes. However, this information is based on static images in an otherwise dynamic system, and successive phases are easily overlooked or misinterpreted. Live-cell imaging and time-lapse microscopy, in which living cells can be followed for hours or even days in a more or less continuous fashion, are therefore very informative. The protocol described here allows for the investigation of the fate of chemotherapeutic nanoparticles after the delivery of doxorubicin (dox) in living cells. Dox is an intercalating agent that must be released from its nanocarrier to become biologically active. In spite of its clinical registration for more than two decades, its uptake, breakdown, and drug release are still not fully understood. This article explores the hypothesis that lipid-based nanoparticles are taken up by the tumor cells and are slowly degraded. Released dox is then translocated to the nucleus. To prevent fixation artifacts, live-cell imaging and time-lapse microscopy, described in this experimental procedure, can be applied.