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Toxicity Reduction and Efficacy Promotion of Doxorubicin in the Treatment of Breast Tumors Assisted by Enhanced Oral Absorption of Curcumin-Loaded Lipid–Polyester Mixed Nanoparticles
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-11-17 , DOI: 10.1021/acs.molpharmaceut.0c00718 Na Wang 1 , Ying Zhang , Hongbing Liu , Andong Wang 2 , Tianyang Ren 3 , Jingxin Gou , Yu Zhang , Tian Yin , Haibing He , Xing Tang
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-11-17 , DOI: 10.1021/acs.molpharmaceut.0c00718 Na Wang 1 , Ying Zhang , Hongbing Liu , Andong Wang 2 , Tianyang Ren 3 , Jingxin Gou , Yu Zhang , Tian Yin , Haibing He , Xing Tang
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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-b-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 × 10–6 of curcumin versus 55.43 ± 6.06 × 10–6 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.
中文翻译：
姜黄素脂质-聚酯混合纳米颗粒增强口服吸收辅助阿霉素治疗乳腺肿瘤的毒性降低和疗效促进
姜黄素 (CUR) 是一种从姜黄中提取的多酚，具有抗癌和抗炎特性。但其水溶性、稳定性和口服生物利用度较差。为了克服这些限制，配制了嵌入肠溶聚合物-EudragitL100-55(Eu) 的脂质-聚酯混合纳米颗粒 (NPs) (CUR-NPs-Eu)。由mPEG- b- PCL组成的 NPs具有由中链甘油三酯 (MCT) 和聚（ε-己内酯）（PCL）组成的混合核心，用于增强载药量。MCT含量为10%的CUR-NPs粒径为121.2±16.8 nm，ζ电位为-16.25±1.38 mV，载药量为9.8%，包封率为87.4%。与单独的 CUR (1.98 ± 0.94 × 10 –6姜黄素与 55.43 ± 6.06 × 10 –6cm/s 的姜黄素纳米颗粒），因为吸收过程中存在非分离的纳米结构。CUR-NPs-Eu 的绝对生物利用度为 7.14%，与 CUR 悬浮液 (CUR-Sus) 的 1.08% 相比有了显着提高。因此，在异种移植 4T1 荷瘤小鼠中，由于 CUR 的口服生物利用度增加，注意到心脏和肿瘤中药物积累增加。CUR 的化学增敏作用归因于其减少 NF-κB 的作用（单独使用 DOX 为 148 ± 11.83，而联合治疗为 104 ± 8.71，ng/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 相关。该研究利用 NPs-Eu 制剂带来的口服有效性促进作用，部分说明了 CUR 的化学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渗透性差的药物方面的能力。
更新日期：2020-12-07
中文翻译：
姜黄素脂质-聚酯混合纳米颗粒增强口服吸收辅助阿霉素治疗乳腺肿瘤的毒性降低和疗效促进
姜黄素 (CUR) 是一种从姜黄中提取的多酚，具有抗癌和抗炎特性。但其水溶性、稳定性和口服生物利用度较差。为了克服这些限制，配制了嵌入肠溶聚合物-EudragitL100-55(Eu) 的脂质-聚酯混合纳米颗粒 (NPs) (CUR-NPs-Eu)。由mPEG- b- PCL组成的 NPs具有由中链甘油三酯 (MCT) 和聚（ε-己内酯）（PCL）组成的混合核心，用于增强载药量。MCT含量为10%的CUR-NPs粒径为121.2±16.8 nm，ζ电位为-16.25±1.38 mV，载药量为9.8%，包封率为87.4%。与单独的 CUR (1.98 ± 0.94 × 10 –6姜黄素与 55.43 ± 6.06 × 10 –6cm/s 的姜黄素纳米颗粒），因为吸收过程中存在非分离的纳米结构。CUR-NPs-Eu 的绝对生物利用度为 7.14%，与 CUR 悬浮液 (CUR-Sus) 的 1.08% 相比有了显着提高。因此，在异种移植 4T1 荷瘤小鼠中，由于 CUR 的口服生物利用度增加，注意到心脏和肿瘤中药物积累增加。CUR 的化学增敏作用归因于其减少 NF-κB 的作用（单独使用 DOX 为 148 ± 11.83，而联合治疗为 104 ± 8.71，ng/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 相关。该研究利用 NPs-Eu 制剂带来的口服有效性促进作用，部分说明了 CUR 的化学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渗透性差的药物方面的能力。
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