School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang 110016, China.
School of Pharmacy, Nantong University, Nantong 226001, China.
Mol Pharm. 2020 Dec 7;17(12):4533-4547. doi: 10.1021/acs.molpharmaceut.0c00718. Epub 2020 Nov 17.
Curcumin (CUR), a polyphenol derived from turmeric, exhibits anticancer and anti-inflammatory properties. However, it has poor water solubility, stability, and oral bioavailability. To overcome these limitations, lipid-polyester mixed nanoparticles (NPs) embedded in enteric polymer-EudragitL100-55(Eu) were formulated (CUR-NPs-Eu). NPs composed of mPEG--PCL have a hybrid core made up of middle chain triglyceride (MCT) and poly(ε-caprolactone) (PCL) for enhancing drug loading. The CUR-NPs with MCT content of 10% had a particle size of 121.2 ± 16.8 nm, ζ potential of -16.25 ± 1.38 mV, drug loading of 9.8%, and encapsulation efficiency of 87.4%. The transport of the CUR-NPs-Eu across Caco-2 monolayers is enhanced compared with CUR alone (1.98 ± 0.94 × 10 of curcumin versus 55.43 ± 6.06 × 10 cm/s of curcumin-loaded NPs) because of the non-disassociated nanostructure during absorption. The absolute bioavailability of CUR-NPs-Eu was 7.14%, which was drastically improved from 1.08% of the CUR suspension (CUR-Sus). Therefore, in the xenograft 4T1 tumor-bearing mice, increased drug accumulation in heart and tumor was noticed because of enhanced oral bioavailability of CUR. The chemosensitizing effect of CUR was attributed to its NF-κB reduction effect (148 ± 11.83 of DOX alone versus 104 ± 8.71 of combined therapy, ng/g tissue). The cardioprotective effect of CUR was associated with maintenance of cardiac antioxidant enzyme activity and down-regulation of NF-κB. This study provided a partial illustration of the mechanisms of chemosensitizing and cardioprotective effects of CUR utilizing the oral availability promotion effect brought by the NPs-Eu formulation. And these results further demonstrated that the capability of this NPs-Eu system in oral delivery of poorly soluble and poorly permeable drugs.
姜黄素（CUR）是一种源自姜黄的多酚，具有抗癌和抗炎特性。然而，它的水溶性、稳定性和口服生物利用度较差。为了克服这些限制，用肠溶聚合物 - 聚（EudragitL100-55）（Eu）包埋的脂质聚酯混合纳米粒（NPs）被制成（CUR-NPs-Eu）。由 mPEG--PCL 组成的 NPs 具有由中链甘油三酯（MCT）和聚（ε-己内酯）（PCL）组成的混合核，用于增强药物负载。MCT 含量为 10%的 CUR-NPs 的粒径为 121.2 ± 16.8nm，ζ 电位为-16.25 ± 1.38mV，药物载量为 9.8%，包封效率为 87.4%。与单独的 CUR 相比，CUR-NPs-Eu 穿过 Caco-2 单层的转运得到增强（1.98 ± 0.94×10 的 CUR 与 55.43 ± 6.06×10 的负载 CUR 的 NPs 的 curcumin cm/s），因为在吸收过程中纳米结构未解离。CUR-NPs-Eu 的绝对生物利用度为 7.14%，与 CUR 混悬液（CUR-Sus）的 1.08%相比有了显著提高。因此，在异种移植 4T1 荷瘤小鼠中，由于 CUR 口服生物利用度的提高，注意到心脏和肿瘤中的药物积累增加。CUR 的化疗增敏作用归因于其 NF-κB 降低作用（单独使用 DOX 为 148 ± 11.83ng/g 组织，联合治疗为 104 ± 8.71ng/g 组织）。CUR 的心脏保护作用与维持心脏抗氧化酶活性和下调 NF-κB 有关。这项研究利用 NPs-Eu 制剂带来的口服可用性促进作用，部分说明了 CUR 的化疗增敏和心脏保护作用的机制。这些结果进一步证明了这种 NPs-Eu 系统在口服递送难溶性和低渗透性药物方面的能力。
