Our objective of this study is to design and develop a polyethylene glycol (PEG₂₀₀₀)-modified multiwall carbon nanotube (PEGylated MWCNT) formulation for oral controlled metronomic chemotherapeutic drug delivery. Multiwall carbon nanotubes undergo various chemical modifications including oxidation with strong acids, conjugation of polyethylene glycol, and coating with cellulose acetate phthalate which resulted in the formation of aqueous dispersion and prevention of drug degradation in acidic environment. Advanced analytical procedure such as Fourier transform infra-red, X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis, transmission electron microscopy, and dynamic light scattering techniques were used to evaluate physicochemical characterization. We also performed in vitro cytotoxic study by MTT assay and results revealed that carboplatin-loaded PEGylated MWCNTs did not show significant detrimental effect on the viability of MDA-MB-231 (human breast cancer) cells. The maximum encapsulation and drug-loading capacity were determined to be 71.58 ± 0.04 and 39.62 ± 0.07%, respectively. The release of carboplatin from PEGylated MWCNTs was investigated at simulated intestinal fluid (SIF), pH 6.8, after optimizing at simulated gastric fluid (SGF), pH 1.2, by enteric coating. Enteric-coated PEGylated MWCNTs exhibit pH-responsive drug activity in a sustained manner especially at pH 6.8. This surface modification strongly suggests that PEGylated MWCNTs could be a potential carrier for metronomic chemotherapeutic agent for high drug resistance, drug with maximum adverse effect and poorly oral bioavailable drugs.

中文翻译：

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载卡铂的聚乙二醇化多壁碳纳米管的基因组化学疗法：在人类乳腺癌中的合成，表征和体外毒性

我们这项研究的目的是设计和开发聚乙二醇（PEG ₂₀₀₀）修饰的多壁碳纳米管（PEG化MWCNT）配方，用于口服控制的节拍式化学治疗药物递送。多壁碳纳米管经历了各种化学修饰，包括用强酸氧化，聚乙二醇共轭和用邻苯二甲酸乙酸纤维素酯包被，从而形成水分散体并防止药物在酸性环境中降解。先进的分析程序，如傅立叶变换红外，X射线衍射，差示扫描量热法，热重分析，透射电子显微镜和动态光散射技术被用于评估理化特性。我们还通过MTT分析进行了体外细胞毒性研究，结果表明，载有卡铂的PEG化MWCNT对MDA-MB-231（人乳腺癌）细胞的生存能力未显示明显的有害作用。测定的最大包封量和载药量分别为71.58±0.04和39.62±0.07％。通过肠溶包衣在模拟胃液（SGF）pH为1.2进行优化后，在模拟肠液（SIF）pH为6.8的条件下研究了卡铂从PEG化MWCNT中的释放。肠溶衣的PEG化MWCNTs持续表现出pH响应的药物活性，尤其是在pH 6.8时。这种表面修饰强烈表明，聚乙二醇化的MWCNTs可能是节律性化学治疗剂的潜在载体，可实现高耐药性，