Quintana-Contardo Sebastián, Donoso-González Orlando, Lang Erika, Guerrero Ariel R, Noyong Michael, Simon Ulrich, Kogan Marcelo J, Yutronic Nicolás, Sierpe Rodrigo
Departamento de Química, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Ñuñoa, Santiago 7800003, Chile.
Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santos Dumont 964, Independencia, Santiago 8380494, Chile.
Pharmaceutics. 2023 Jan 30;15(2):458. doi: 10.3390/pharmaceutics15020458.
Dacarbazine (DB) is an antineoplastic drug extensively used in cancer therapy. However, present limitations on its performance are related to its low solubility, instability, and non-specificity. To overcome these drawbacks, DB was included in β-cyclodextrin (βCD), which increased its aqueous solubility and stability. This new βCD@DB complex has been associated with plasmonic gold nanoparticles (AuNPs), and polyethylene glycol (PEG) has been added in the process to increase the colloidal stability and biocompatibility. Different techniques revealed that DB allows for a dynamic inclusion into βCD, with an association constant of 80 M and a degree of solubilization of 0.023, where βCD showed a loading capacity of 16%. The partial exposure of the NH group in the included DB allows its interaction with AuNPs, with a loading efficiency of 99%. The PEG-AuNPs-βCD@DB nanosystem exhibits an optical plasmonic absorption at 525 nm, a surface charge of -29 mV, and an average size of 12 nm. Finally, laser irradiation assays showed that DB can be released from this platform in a controlled manner over time, reaching a concentration of 56 μg/mL (43% of the initially loaded amount), which, added to the previous data, validates its potential for drug delivery applications. Therefore, the novel nanosystem based on βCD, AuNPs, and PEG is a promising candidate as a new nanocarrier for DB.
达卡巴嗪（DB）是一种广泛用于癌症治疗的抗肿瘤药物。然而，其目前性能的局限性与低溶解度、不稳定性和非特异性有关。为了克服这些缺点，将DB包载入β-环糊精（βCD）中，这提高了其水溶性和稳定性。这种新型的βCD@DB复合物已与等离子体金纳米颗粒（AuNPs）结合，并且在该过程中添加了聚乙二醇（PEG）以提高胶体稳定性和生物相容性。不同技术表明，DB能够动态包入βCD中，缔合常数为80 M，增溶程度为0.023，其中βCD的负载量为16%。包入的DB中NH基团的部分暴露使其能够与AuNPs相互作用，负载效率为99%。PEG-AuNPs-βCD@DB纳米系统在525 nm处表现出光学等离子体吸收，表面电荷为-29 mV，平均尺寸为12 nm。最后，激光照射试验表明，DB可以从该平台随时间以可控方式释放，达到56 μg/mL的浓度（占初始负载量的43%），结合先前的数据，证实了其在药物递送应用中的潜力。因此，基于βCD、AuNPs和PEG的新型纳米系统是一种很有前景的DB新型纳米载体候选物。
