Kumari Surabhi, Nehra Anuj, Gupta Kshitij, Puri Anu, Kumar Vinay, Singh Krishna Pal, Kumar Mukesh, Sharma Ashutosh
Bio-Nanotechnology Research Laboratory, Biophysics Unit, College of Basic Science & Humanities, G.B. Pant University of Agriculture and Technology, Pantnagar 263145, Uttarakhand, India.
Department of Physics, Guru Jambheshwar University of Science and Technology, Hisar 125001, Haryana, India.
Pharmaceutics. 2023 Feb 15;15(2):649. doi: 10.3390/pharmaceutics15020649.
In this study, the authors have designed biocompatible nano-vesicles using graphene oxide (GO) for the release of chlorambucil (CHL) drugs targeting cancerous cells. The GO sheets were first sulfonated and conjugated with folic acid (FA) molecules for controlled release and high loading efficiency of CHL. The chlorambucil (CHL) drug loading onto the functionalized GO surface was performed through π-π stacking and hydrophobic interactions with the aromatic planes of GO. The drug loading and "in vitro" release from the nano-vesicles at different pH were studied. The average particle size, absorption, and loading efficiency (%) of FA-conjugated GO sheets (CHL-GO) were observed to be 300 nm, 58%, and 77%, respectively. The drug release study at different pH (i.e., 7.4 and 5.5) showed a slight deceleration at pH 7.4 over pH 5.5. The amount of drug released was very small at pH 7.4 in the first hour which progressively increased to 24% after 8 h. The rate of drug release was faster at pH 5.5; initially, 16% to 27% in the first 3 h, and finally it reached 73% after 9 h. These observations indicate that the drug is released more rapidly at acidic pH with a larger amount of drug-loading ability. The rate of drug release from the CHL-loaded GO was 25% and 75% after 24 h. The biotoxicity study in terms of % cell viability of CHL-free and CHL-loaded GO against human cervical adenocarcinoma cell line was found to have lower cytotoxicity of CHL-loaded nano-vesicles (IC = 18 μM) as compared to CHL-free (IC = 8 μM). It is concluded that a high drug-loading efficiency and controlled release with excellent biotoxicity of CHL-GO offers an excellent application in the biomedical field.
在本研究中，作者设计了使用氧化石墨烯（GO）的生物相容性纳米囊泡，用于释放靶向癌细胞的苯丁酸氮芥（CHL）药物。首先将GO片材磺化并与叶酸（FA）分子共轭，以实现CHL的控释和高负载效率。通过π-π堆积以及与GO芳香平面的疏水相互作用，将苯丁酸氮芥（CHL）药物负载到功能化的GO表面。研究了纳米囊泡在不同pH值下的药物负载和“体外”释放情况。观察到FA共轭GO片材（CHL-GO）的平均粒径、吸收率和负载效率（%）分别为300 nm、58%和77%。在不同pH值（即7.4和5.5）下的药物释放研究表明，与pH 5.5相比，pH 7.4时药物释放略有减速。在pH 7.4时，第1小时释放的药量非常少，8小时后逐渐增加到24%。在pH 5.5时药物释放速率更快；最初，在前3小时为16%至27%，9小时后最终达到73%。这些观察结果表明，在酸性pH值下药物释放更快，且具有更大的载药能力。负载CHL的GO在24小时后的药物释放率为25%和75%。关于不含CHL和负载CHL的GO对人宫颈腺癌细胞系的细胞活力百分比的生物毒性研究发现，与不含CHL的情况（IC = 8 μM）相比，负载CHL的纳米囊泡（IC = 18 μM）的细胞毒性较低。得出结论，CHL-GO具有高载药效率、控释以及优异的生物毒性，在生物医学领域具有出色的应用前景。
