Passively Targeted Curcumin-Loaded PEGylated PLGA Nanocapsules for Colon Cancer Therapy In Vivo.
Passively Targeted Curcumin-Loaded PEGylated PLGA Nanocapsules for Colon Cancer Therapy In Vivo.
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DOI：
10.1002/smll.201403799
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Al-Jamal KT
中科院分区：
文献类型：
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作者：
Klippstein R;Wang JT;El-Gogary RI;Bai J;Mustafa F;Rubio N;Bansal S;Al-Jamal WT;Al-Jamal KT
姜黄素的生物半衰期短、水溶性差等缺点阻碍了其在癌症和其他慢性疾病治疗中的临床应用。基于纳米技术的药物递送系统具有增强用于全身递送的难溶性药物的功效的潜力。本研究提出了使用聚（乳酸-羟基乙酸）（PLGA）为基础的聚合物油芯纳米胶囊（NC）的姜黄素负载和交付后，全身注射到小鼠结肠癌。制备不同油组合物的制剂并表征其姜黄素负载、物理化学性质和保质期稳定性。结果表明，与先前报道的NC相比，蓖麻油芯的基于PLGA的NC实现了高载药效率（约18%w（药物）/w（聚合物）%）。负载姜黄素的NC在CT 26细胞中比游离药物更有效地内化，并在体外发挥治疗活性，导致细胞凋亡和阻断细胞周期。此外，与非PEG化NC相比，配制的NC表现出延长的血液循环特征，并且在全身给药后在小鼠的皮下CT 26肿瘤中蓄积。通过光学和单光子发射计算机断层扫描/计算机断层扫描（SPECT/CT）成像证实了结果。进行体内生长延迟研究，并且与空NC注射的动物相比，实现了显著更小的肿瘤体积。这项研究显示了配方NC治疗结肠癌的巨大潜力。
Clinical applications of curcumin for the treatment of cancer and other chronic diseases have been mainly hindered by its short biological half-life and poor water solubility. Nanotechnology-based drug delivery systems have the potential to enhance the efficacy of poorly soluble drugs for systemic delivery. This study proposes the use of poly(lactic-co-glycolic acid) (PLGA)-based polymeric oil-cored nanocapsules (NCs) for curcumin loading and delivery to colon cancer in mice after systemic injection. Formulations of different oil compositions are prepared and characterized for their curcumin loading, physico-chemical properties, and shelf-life stability. The results indicate that castor oil-cored PLGA-based NC achieves high drug loading efficiency (≈18% w(drug)/w(polymer)%) compared to previously reported NCs. Curcumin-loaded NCs internalize more efficiently in CT26 cells than the free drug, and exert therapeutic activity in vitro, leading to apoptosis and blocking the cell cycle. In addition, the formulated NC exhibits an extended blood circulation profile compared to the non-PEGylated NC, and accumulates in the subcutaneous CT26-tumors in mice, after systemic administration. The results are confirmed by optical and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. In vivo growth delay studies are performed, and significantly smaller tumor volumes are achieved compared to empty NC injected animals. This study shows the great potential of the formulated NC for treating colon cancer.