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合成与表征纤维素纤维修饰的磷酸锌/羟基磷灰石核壳作为顺铂的增强载体:载药、释放及细胞毒性。

Synthesis and characterization of cellulose fibers modified zinc phosphate/hydroxyapatite core-shell as enhanced carrier of cisplatin: Loading, release, and cytotoxicity.

机构信息

Biology Department, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt; Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia.

出版信息

Int J Biol Macromol. 2024 Oct;277(Pt 3):134169. doi: 10.1016/j.ijbiomac.2024.134169. Epub 2024 Aug 2.

Abstract

The uncontrolled administration of the cisplatin drug (CPTN) resulted in numerous drawbacks. Therefore, effective, affordable, and biocompatible delivery systems were suggested to regulate the loading, release, and therapeutic effect of CPTN. Zinc phosphate/hydroxyapatite hybrid form (ZP/HP) and core-shell nano-rod morphology, as well as its functionalized derivative with cellulose (CF@ZP/HP), were synthesized by the facile dissolution precipitation method followed by mixing with cellulose fibers, respectively. The developed CF@ZP/HP displayed remarkable enhanced CPTN loading properties (418.2 mg/g) as compared to ZP/HP (259.8 mg/g). The CPTN loading behaviors into CF@ZP/HP follow the Langmuir isotherm properties (R > 0.98) in addition to the kinetic activities of the pseudo-first-order model (R > 0.96). The steric assessment validates the notable increase in the existing loading receptors after the functionalization of ZP/HP with CF from 57.7 mg/g (ZP/HP) to 90.5 mg/g. The functionalization also impacted the capacity of each existing receptor to be able to ensure 5 CPTN molecules. This, in addition to the loading energies (<40 kJ/mol), donates the loading of CPTN by physical multi-molecular processes and in vertical orientation. The CPTN releasing patterns of CF@ZP/HP exhibit slow and controlled properties (95.7 % after 200 h at pH 7.4 and 100 % after 120 h at pH 5.5), but faster than the properties of ZP/HP. The kinetic modeling of the release activities together with the diffusion exponent (>0.45) reflected the release of CPTN according to both erosion and diffusion mechanisms. The loading of CPTN into both ZP/HP and CF@ZP/HP also resulted in a marked enhancement in the anticancer activity of CPTN against human cervical epithelial malignancies (HeLa) (cell viability = 5.6 % (CPTN), 3.2 % (CPTN loaded ZP/HP), and 1.12 % (CPTN loaded CF@ZP/HP)).

摘要

顺铂药物(CPTN)的不受控制的给药导致了许多缺点。因此,提出了有效、经济实惠且生物相容的递送系统,以调节 CPTN 的负载、释放和治疗效果。锌磷酸盐/羟基磷灰石杂化形式(ZP/HP)和核壳纳米棒形态,以及其与纤维素(CF@ZP/HP)的功能化衍生物,通过简单的溶解沉淀法合成,然后分别与纤维素纤维混合。与 ZP/HP(259.8mg/g)相比,开发的 CF@ZP/HP 显示出显著增强的 CPTN 负载性能(418.2mg/g)。CPTN 负载行为遵循朗缪尔等温线性质(R>0.98),此外还有伪一级模型的动力学活性(R>0.96)。空间评估验证了在 ZP/HP 用 CF 功能化后,现有负载受体的数量显著增加,从 57.7mg/g(ZP/HP)增加到 90.5mg/g。功能化还影响了每个现有受体的能力,以确保能够负载 5 个 CPTN 分子。这一点,加上负载能(<40kJ/mol),有助于 CPTN 通过物理多分子过程以垂直取向进行负载。CF@ZP/HP 的 CPTN 释放模式表现出缓慢和可控的特性(在 pH7.4 下 200 小时后释放 95.7%,在 pH5.5 下 120 小时后释放 100%),但比 ZP/HP 的释放速度快。释放活性的动力学模型和扩散指数(>0.45)反映了 CPTN 释放遵循侵蚀和扩散机制。CPTN 负载到 ZP/HP 和 CF@ZP/HP 中也显著提高了 CPTN 对人宫颈上皮恶性肿瘤(HeLa)的抗癌活性(细胞活力=5.6%(CPTN),3.2%(CPTN 负载 ZP/HP)和 1.12%(CPTN 负载 CF@ZP/HP))。

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