PDF(Pubmed)
Abstract：
UNASSIGNED: Gemcitabine is the first line and the gold standard drug for pancreatic cancer. However, the anticancer efficacy is severely limited by its instability and poor cellular uptake. To enhance the clinical efficacy of gemcitabine, we constructed a novel nanodrug delivery system based on amphiphilic dendrimers and aliphatic gemcitabine prodrug.
UNASSIGNED: An aliphatic gemcitabine prodrug and a small amphiphilic dendrimer were synthesized and characterized by high resolution mass spectrometry (HRMS) as well as nuclear magnetic resonance (NMR). Then the aliphatic gemcitabine prodrug was encapsulated into the small amphiphilic dendrimer by film dispersion method, resulting in a novel nanodrug delivery system. Subsequently, the size, morphology, drug loading, stability, drug release profiles, cell uptake, toxicity, the anticancer activity and in vivo distribution of the new developed gemcitabine delivery system were systematically evaluated by different technical methods, including transmission electron microscopy (TEM), dynamic light-scattering (DLS), ultraviolet spectrophotometer, flow cytometry, in vivo imaging system etc.
UNASSIGNED: We developed a novel nanodrug delivery system of gemcitabine using amphiphilic dendrimer. This dendrimer-based gemcitabine nanoformulation reported here possess a high drug loading of 33%. With the features of small size, stable formulation and pH-responsive drug release, the obtained gemcitabine nanoformulation could effectively accumulate in tumor site and rapid uptake in cells. Finally, the gemcitabine nanoformulation displayed more potent anticancer activity compared to free gemcitabine both in vitro and in vivo. Moreover, the nanodrug displayed greatly reduced adverse effects and satisfactory biocompatibility.
UNASSIGNED: Benefiting the advantageous features of both amphiphilic dendrimers and nanotechnology-based drug delivery, this gemcitabine nanosystem constitutes a promising therapeutic candidate for pancreatic cancer treatment. This study also underlines the potential use of self-assembling amphiphilic dendrimer-based nanotechnology for improving drug efficacy as well as reducing drug toxicity.
UNASSIGNED: An aliphatic gemcitabine prodrug and a small amphiphilic dendrimer were synthesized and characterized by high resolution mass spectrometry (HRMS) as well as nuclear magnetic resonance (NMR). Then the aliphatic gemcitabine prodrug was encapsulated into the small amphiphilic dendrimer by film dispersion method, resulting in a novel nanodrug delivery system. Subsequently, the size, morphology, drug loading, stability, drug release profiles, cell uptake, toxicity, the anticancer activity and in vivo distribution of the new developed gemcitabine delivery system were systematically evaluated by different technical methods, including transmission electron microscopy (TEM), dynamic light-scattering (DLS), ultraviolet spectrophotometer, flow cytometry, in vivo imaging system etc.
UNASSIGNED: We developed a novel nanodrug delivery system of gemcitabine using amphiphilic dendrimer. This dendrimer-based gemcitabine nanoformulation reported here possess a high drug loading of 33%. With the features of small size, stable formulation and pH-responsive drug release, the obtained gemcitabine nanoformulation could effectively accumulate in tumor site and rapid uptake in cells. Finally, the gemcitabine nanoformulation displayed more potent anticancer activity compared to free gemcitabine both in vitro and in vivo. Moreover, the nanodrug displayed greatly reduced adverse effects and satisfactory biocompatibility.
UNASSIGNED: Benefiting the advantageous features of both amphiphilic dendrimers and nanotechnology-based drug delivery, this gemcitabine nanosystem constitutes a promising therapeutic candidate for pancreatic cancer treatment. This study also underlines the potential use of self-assembling amphiphilic dendrimer-based nanotechnology for improving drug efficacy as well as reducing drug toxicity.
摘要：
■吉西他滨是胰腺癌的一线和黄金标准药物。然而,抗癌功效受到其不稳定性和细胞摄取差的严重限制。为了提高吉西他滨的临床疗效，我们构建了基于两亲性树状聚合物和脂肪族吉西他滨前药的新型纳米药物递送系统。
■合成了脂族吉西他滨前药和小的两亲性树枝状聚合物，并通过高分辨率质谱（HRMS）和核磁共振（NMR）进行了表征。然后通过薄膜分散法将脂肪族吉西他滨前药包封到小的两亲性树枝状聚合物中，产生了一种新型的纳米药物递送系统。随后，尺寸,形态学,药物装载，稳定性,药物释放概况，细胞摄取，毒性,通过不同的技术方法系统地评估了新开发的吉西他滨给药系统的抗癌活性和体内分布，包括透射电子显微镜（TEM），动态光散射(DLS),紫外分光光度计,流式细胞术,体内成像系统等.
■我们使用两亲性树枝状聚合物开发了吉西他滨的新型纳米药物递送系统。本文报道的这种基于树枝状聚合物的吉西他滨纳米制剂具有33%的高载药量。具有体积小的特点，稳定的配方和pH响应的药物释放，获得的吉西他滨纳米制剂可以有效地在肿瘤部位积累并在细胞中快速吸收。最后,与游离吉西他滨相比，吉西他滨纳米制剂在体外和体内均显示出更有效的抗癌活性。此外，纳米药物显示出大大降低的不良反应和令人满意的生物相容性。
■得益于两亲性树枝状聚合物和基于纳米技术的药物递送的有利特征，这种吉西他滨纳米系统是胰腺癌治疗的一个有前景的候选药物.这项研究还强调了基于自组装两亲性树枝状聚合物的纳米技术在提高药物疗效以及降低药物毒性方面的潜在用途。
■合成了脂族吉西他滨前药和小的两亲性树枝状聚合物，并通过高分辨率质谱（HRMS）和核磁共振（NMR）进行了表征。然后通过薄膜分散法将脂肪族吉西他滨前药包封到小的两亲性树枝状聚合物中，产生了一种新型的纳米药物递送系统。随后，尺寸,形态学,药物装载，稳定性,药物释放概况，细胞摄取，毒性,通过不同的技术方法系统地评估了新开发的吉西他滨给药系统的抗癌活性和体内分布，包括透射电子显微镜（TEM），动态光散射(DLS),紫外分光光度计,流式细胞术,体内成像系统等.
■我们使用两亲性树枝状聚合物开发了吉西他滨的新型纳米药物递送系统。本文报道的这种基于树枝状聚合物的吉西他滨纳米制剂具有33%的高载药量。具有体积小的特点，稳定的配方和pH响应的药物释放，获得的吉西他滨纳米制剂可以有效地在肿瘤部位积累并在细胞中快速吸收。最后,与游离吉西他滨相比，吉西他滨纳米制剂在体外和体内均显示出更有效的抗癌活性。此外，纳米药物显示出大大降低的不良反应和令人满意的生物相容性。
■得益于两亲性树枝状聚合物和基于纳米技术的药物递送的有利特征，这种吉西他滨纳米系统是胰腺癌治疗的一个有前景的候选药物.这项研究还强调了基于自组装两亲性树枝状聚合物的纳米技术在提高药物疗效以及降低药物毒性方面的潜在用途。
