载顺铂壳聚糖纳米粒子的表征及利妥昔单抗偶联表面作为靶向的可注射型纳米制剂用于癌症的治疗。
Characterization of cisplatin-loaded chitosan nanoparticles and rituximab-linked surfaces as target-specific injectable nano-formulations for combating cancer.
机构信息
Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, Jazan University, P.O. Box 114, Jazan, 45142, Kingdom of Saudi Arabia.
出版信息
Sci Rep. 2022 Jan 10;12(1):468. doi: 10.1038/s41598-021-04427-w.
The present study was carried out to develop cisplatin-loaded chitosan nanoparticles (CCNP) and cisplatin-loaded chitosan nanoparticle surface linked to rituximab (mAbCCNP) as targeted delivery formulations. The two formulations (CCNP and mAbCCNP) exhibited significant physicochemical properties. The zetapotential (ZP) values of CCNP and mAbCCNP were 30.50 ± 5.64 and 26.90 ± 9.09 mV, respectively; while their particle sizes were 308.10 ± 1.10 and 349.40 ± 3.20 z.d.nm, respectively. The poly dispersity index (PDI) of CCNP was 0.257 ± 0.030 (66.6% PDI), while that of mAbCCNP was 0.444 ± 0.007 (57.60% PDI). Differential scanning calorimetry (DSC) revealed that CCNP had endothermic peaks at temperatures ranging from 135.50 to 157.69 °C. A sharp exothermic peak was observed at 95.79 °C, and an endothermic peak was observed at 166.60 °C. The XRD study on CCNP and mAbCCNP revealed distinct peaks at 2θ. Four peaks at 35.38°, 37.47°, 49.29°, and 59.94° corresponded to CCNP, while three distinct peaks at 36.6°, 49.12°, and 55.08° corresponded to mAbCCNP. The in vitro release of cisplatin from nanoparticles followed zero order kinetics in both CCNP and mAbCCNP. The profile for CCNP showed 43.80% release of cisplatin in 6 h (R = 0.9322), indicating linearity of release with minimal deviation. However, the release profile of mAbCCNP showed 22.52% release in 4 h (R = 0.9416), indicating linearity with sustained release. In vitro cytotoxicity studies on MCF-7 ATCC human breast cancer cell line showed that CCNP exerted good cytotoxicity, with IC of 4.085 ± 0.065 µg/mL. However, mAbCCNP did not elicit any cytotoxic effect. At a dose of 4.00 µg/mL cisplatin induced early apoptosis and late apoptosis, chromatin condensation, while it produced secondary necrosis at a dose of 8.00 µg/mL. Potential delivery system for cisplatin CCNP and mAbCCNP were successfully formulated. The results indicated that CCNP was a more successful formulation than mAbCCNP due to lack of specificity of rituximab against MCF-7 ATCC human breast cancer cells.
本研究旨在开发顺铂负载壳聚糖纳米粒子（CCNP）和顺铂负载壳聚糖纳米粒子表面连接利妥昔单抗（mAbCCNP）作为靶向递药制剂。两种制剂（CCNP 和 mAbCCNP）表现出显著的物理化学性质。CCNP 和 mAbCCNP 的 Zeta 电位（ZP）值分别为 30.50 ± 5.64 和 26.90 ± 9.09 mV；粒径分别为 308.10 ± 1.10 和 349.40 ± 3.20 z.d.nm。CCNP 的多分散指数（PDI）为 0.257 ± 0.030（66.6%PDI），而 mAbCCNP 的 PDI 为 0.444 ± 0.007（57.60%PDI）。差示扫描量热法（DSC）显示，CCNP 在 135.50 至 157.69°C 的温度范围内有吸热峰。在 95.79°C 处观察到一个明显的放热峰，在 166.60°C 处观察到一个吸热峰。CCNP 和 mAbCCNP 的 XRD 研究显示在 2θ 处有明显的峰。在 35.38°、37.47°、49.29°和 59.94°处的四个峰对应于 CCNP，而在 36.6°、49.12°和 55.08°处的三个明显峰对应于 mAbCCNP。顺铂从纳米粒子中的体外释放遵循 CCNP 和 mAbCCNP 中的零级动力学。CCNP 的曲线显示在 6 小时内释放了 43.80%的顺铂（R=0.9322），表明释放具有线性，偏差最小。然而，mAbCCNP 的释放曲线显示在 4 小时内释放了 22.52%的顺铂（R=0.9416），表明释放具有线性，且持续释放。在 MCF-7 ATCC 人乳腺癌细胞系上进行的体外细胞毒性研究表明，CCNP 表现出良好的细胞毒性，IC 为 4.085 ± 0.065 μg/mL。然而，mAbCCNP 没有产生任何细胞毒性作用。在 4.00μg/mL 顺铂诱导早期凋亡和晚期凋亡、染色质浓缩，而在 8.00μg/mL 顺铂诱导次级坏死。顺铂的潜在给药系统 CCNP 和 mAbCCNP 已成功构建。结果表明，由于利妥昔单抗对 MCF-7 ATCC 人乳腺癌细胞缺乏特异性，CCNP 是一种比 mAbCCNP 更成功的制剂。
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