Niza Enrique, Nieto-Jiménez Cristina, Noblejas-López María Del Mar, Bravo Iván, Castro-Osma José Antonio, Cruz-Martínez Felipe de la, Buchaca Marc Martínez de Sarasa, Posadas Inmaculada, Canales-Vázquez Jesús, Lara-Sanchez Agustín, Hermida-Merino Daniel, Solano Eduardo, Ocaña Alberto, Alonso-Moreno Carlos
Dpto. Inorgánica, Orgánica y Bioquímica. School of Pharmacy, University of Castilla-La Mancha, 02071 Albacete, Spain.
Oncología traslacional, Centro Regional de Investigaciones Biomédicas, University of Castilla, La Mancha, Spain.
Nanomaterials (Basel). 2019 Aug 27;9(9):1208. doi: 10.3390/nano9091208.
The effect on the activity in breast cancer models of the small tyrosine kinase inhibitor dasatinib (DAS), either alone or in combination with other antitumoral agents, has been recently explored. However, DAS is characterized by its low and highly pH-dependent solubility, which could lead to poor uptake of the drug limiting its tumoral efficacy. Thus far, the development of safe and efficient delivery vehicles of DAS to improve the therapeutic efficacy minimizing the toxicity profile is still required. In this work, a biodegradable and biocompatible polyester is assessed, for the first time, as raw material for the generation of polymeric nanoparticles (NPs). NPs of 100 nm with a narrow polydispersity were formulated for the encapsulation of DAS. The enzymatic and cellular degradation of the new drug delivery system has been studied, and the toxicity and blood compatibility evaluated for its potential clinical use. The new material used for the generation of nanoparticles led to encapsulate DAS in an efficient manner with quicker release DAS profile when compared with the FDA-approved biopolymer Polylactide. The new DAS-loaded polymeric nanocarrier gave a superior efficacy when compared to free DAS with no difference in the mechanism of action. The new NPs shown to be a promising DAS delivery system to be further evaluated for breast cancer treatment.
近期已对小酪氨酸激酶抑制剂达沙替尼（DAS）单独或与其他抗肿瘤药物联合使用对乳腺癌模型活性的影响进行了研究。然而，DAS的特点是其溶解度低且高度依赖pH值，这可能导致药物摄取不佳，限制其肿瘤疗效。到目前为止，仍需要开发安全有效的达沙替尼递送载体，以提高治疗效果并将毒性降至最低。在这项工作中，首次评估了一种可生物降解且生物相容的聚酯作为制备聚合物纳米颗粒（NPs）的原材料。制备了粒径为100 nm且多分散性窄的纳米颗粒用于包封达沙替尼。研究了这种新型药物递送系统的酶促降解和细胞降解，并评估了其潜在临床应用的毒性和血液相容性。与美国食品药品监督管理局（FDA）批准的生物聚合物聚丙交酯相比，用于制备纳米颗粒的新材料能够高效包封达沙替尼，且达沙替尼的释放曲线更快。与游离达沙替尼相比，新型载药聚合物纳米载体具有更高的疗效，且作用机制无差异。新型纳米颗粒显示出有望成为一种用于乳腺癌治疗的达沙替尼递送系统，有待进一步评估。
