The goal of the current study was to target 7-ethyl-10-hydroxycamptothecin (SN38) orally to colon tumours by synthesizing a targeting polymer. To achieve the optimum delivery for SN38, initially methoxy-polyethylene glycol (mPEG)-chitosan was synthesized and then nanoparticles were developed through ionic gelation between mPEG-chitosan and hyaluronic acid as a ligand for cell-surface glycoprotein CD44 receptor. The SN38 was loaded in nanoparticles (SN38-NPs) using the non-covalent physical adsorption method. The size of the optimized SN38-NPs was 226.7 nm, encapsulation efficiency was 89.23% and drug content was 7.98 ± 0.54% in the optimum formulation. The attachment of mPEG to chitosan was confirmed by proton nuclear magnetic resonance. The results of differential scanning calorimetry and Fourier transforms infra-red analysis indicated that SN38 existed in amorphous form and functional groups of SN38 protected in the formulations which could be a sign of suitable encapsulation of SN38 in SN38-NPs. In vitro study indicated that SN38-NPs were more potent against the cancer cells than free SN38. The cellular uptake of SN38-NPs improved up to 1.6-fold against human colorectal adenocarcinoma (Caco-2) cells. Moreover, SN38-NPs remarkably demonstrated superior anti-tumor efficacy in contrary to pure SN38. This suggests the advantage of SN38-NPs as a potent oral drug carrier which could be further explored for clinical investigations.

中文翻译：

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用于结肠癌治疗的含有 7-乙基-10-羟基喜树碱的新型聚合物纳米粒子（甲氧基-聚乙二醇-壳聚糖/透明质酸）的合成：体外、离体和体内研究。


当前研究的目标是通过合成靶向聚合物，将 7-乙基-10-羟基喜树碱 (SN38) 口服靶向结肠肿瘤。为了实现 SN38 的最佳递送，首先合成了甲氧基聚乙二醇 (mPEG)-壳聚糖，然后通过 mPEG-壳聚糖和透明质酸之间的离子凝胶化开发纳米颗粒作为细胞表面糖蛋白 CD44 受体的配体。采用非共价物理吸附法将SN38负载到纳米粒子(SN38-NPs)中。优化后的SN38-NPs尺寸为226.7 nm，包封率为89.23%，最佳处方中药物含量为7.98±0.54%。通过质子核磁共振证实了 mPEG 与壳聚糖的附着。差示扫描量热法和傅里叶变换红外分析的结果表明SN38以无定形形式存在并且SN38的官能团在制剂中受到保护，这可能是SN38在SN38-NPs中合适封装的标志。体外研究表明，SN38-NPs 比游离的 SN38 更有效地对抗癌细胞。相对于人结直肠腺癌细胞 (Caco-2)，SN38-NP 的细胞摄取量提高了 1.6 倍。此外，与纯SN38相比，SN38-NPs显着表现出优异的抗肿瘤功效。这表明 SN38-NPs 作为有效的口服药物载体的优势，可以在临床研究中进一步探索。