Thermoresponsive biomaterial system of irinotecan and curcumin for the treatment of colorectal cancer: <i>in-vitro</i> and <i>in-vivo</i> investigations

This study aims to develop a thermoresponsive biomaterial system of irinotecan (IRT) and curcumin (CUR) nano-transferosomal gel (IRT-CUR-NTG) for targeting colorectal cancer (CRC). The IRT-CUR-NTs were statistically optimized and loaded into poloxamer-based thermosensitive gel. Transmission electron microscopy (TEM), Differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) of the IRT-CUR-NTs were performed, whereas pH, gelation time, gelation temperature, gel and mucoadhesive strength of the IRT-CUR-NTG were investigated. <i>In-vitro</i> release and anticancer analyses were explored using HT29 cells. Additionally, <i>in-vivo</i> pharmacokinetics study was investigated followed by histopathological examination and <i>in-vivo</i> anticancer analysis. The PS, PDI, ZP, � of IRT and � of CUR were found to be 136.15 nm, 0.143, −15.5 mV, 95.05% and 85.12%, respectively. IRT-CUR-NTs exhibited spherical shape with no chemical interactions among the constituents. Similarly, IRT-CUR-NTG was homogenous gel suitable for rectal administration. IRT-CUR-NTG manifested prolonged release profiles of IRT and CUR. Moreover, a significantly enhanced (4-fold) bioavailability and no toxicity of IRT-CUR-NTG was observed when compared with conventional gel. IRT-CUR-NTs were found to be more effective against HT29 cell lines. <i>In-vivo</i> antitumor analysis demonstrated significantly reduced tumor volume and tumor mass after treatment with IRT-CUT-NTG, indicating improved antitumor effect. It can be concluded that IRT-CUR-NTG is suitable biomaterial system for colorectal cancer.

本研究旨在开发一款基于伊立替康（irinotecan, IRT）与姜黄素（curcumin, CUR）的热敏性生物材料系统——伊立替康-姜黄素纳米传递体凝胶（IRT-CUR-NTG），用于结直肠癌（colorectal cancer, CRC）的靶向治疗。本研究对IRT-CUR纳米传递体（IRT-CUR-NTs）进行了统计学优化，并将其负载于泊洛沙姆基热敏凝胶中。随后对IRT-CUR-NTs开展了透射电子显微镜（Transmission electron microscopy, TEM）、差示扫描量热法（Differential scanning calorimetry, DSC）及傅里叶变换红外光谱（Fourier-transform infrared spectroscopy, FTIR）表征；同时考察了IRT-CUR-NTG的pH值、胶凝时间、胶凝温度、凝胶强度与黏膜黏附强度。采用HT29细胞开展了体外（in-vitro）释放实验与抗癌活性分析。此外，本研究还开展了体内（in-vivo）药代动力学研究，随后进行了组织病理学检查及体内（in-vivo）抗癌活性分析。结果显示，伊立替康的包封率与姜黄素的包封率分别为95.05%与85.12%，IRT-CUR-NTs的粒径（particle size, PS）、多分散性指数（polydispersity index, PDI）及Zeta电位（Zeta potential, ZP）依次为136.15 nm、0.143与-15.5 mV。IRT-CUR-NTs呈球形形貌，且各组分间未发生化学相互作用。同理，IRT-CUR-NTG为均质性凝胶，适用于直肠给药。IRT-CUR-NTG可实现伊立替康与姜黄素的缓释效果。与传统凝胶相比，IRT-CUR-NTG的生物利用度显著提升4倍，且未观察到毒性反应。IRT-CUR-NTs对HT29细胞系的杀伤活性更强。体内（in-vivo）抗肿瘤实验结果表明，经IRT-CUR-NTG治疗后，肿瘤体积与肿瘤质量均显著降低，提示其抗肿瘤效果得到改善。综上可知，IRT-CUR-NTG是一款适用于结直肠癌治疗的高性能生物材料系统。

搜集汇总

背景与挑战

背景概述

该数据集聚焦于开发一种热响应生物材料系统，结合伊立替康和姜黄素，用于结直肠癌治疗。研究通过体外和体内实验验证了系统的有效性，包括优化纳米转移体凝胶、药物释放分析、抗癌活性评估以及药代动力学研究，结果显示系统能显著提高生物利用度并减少肿瘤体积。数据集涵盖了从材料制备到临床前评估的全过程，为结直肠癌靶向治疗提供了实验数据支持。