Zatta Kelly Cristine, Frank Luiza A, Reolon Luciano Antonio, Amaral-Machado Lucas, Egito Eryvaldo S T, Gremião Maria Palmira Daflon, Pohlmann Adriana Raffin, Guterres Silvia S
Programa de Pós-Graduação em Nanotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre RS 90610-000, Brazil.
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre RS 90610-000, Brazil.
Nanomaterials (Basel). 2018 Jan 30;8(2):75. doi: 10.3390/nano8020075.
Melanoma is the most aggressive and lethal type of skin cancer, with a poor prognosis because of the potential for metastatic spread. The aim was to develop innovative powder formulations for the treatment of metastatic melanoma based on micro- and nanocarriers containing 5-fluorouracil (5FU) for pulmonary administration, aiming at local and systemic action. Therefore, two innovative inhalable powder formulations were produced by spray-drying using chondroitin sulfate as a structuring polymer: (a) 5FU nanoparticles obtained by piezoelectric atomization (5FU-NS) and (b) 5FU microparticles of the mucoadhesive agent Methocel™ F4M for sustained release produced by conventional spray drying (5FU-MS). The physicochemical and aerodynamic were evaluated in vitro for both systems, proving to be attractive for pulmonary delivery. The theoretical aerodynamic diameters obtained were 0.322 ± 0.07 µm (5FU-NS) and 1.138 ± 0.54 µm (5FU-MS). The fraction of respirable particles (FR%) were 76.84 ± 0.07% (5FU-NS) and 55.01 ± 2.91% (5FU-MS). The in vitro mucoadhesive properties exhibited significant adhesion efficiency in the presence of Methocel™ F4M. 5FU-MS and 5FU-NS were tested for their cytotoxic action on melanoma cancer cells (A2058 and A375) and both showed a cytotoxic effect similar to 5FU pure at concentrations of 4.3 and 1.7-fold lower, respectively.
黑色素瘤是最具侵袭性和致命性的皮肤癌类型，由于存在转移扩散的可能性，其预后较差。本研究旨在开发基于含5-氟尿嘧啶（5FU）的微载体和纳米载体的创新粉末制剂，用于肺部给药治疗转移性黑色素瘤，以期实现局部和全身作用。因此，通过喷雾干燥，以硫酸软骨素作为结构聚合物制备了两种创新的可吸入粉末制剂：（a）通过压电雾化获得的5FU纳米颗粒（5FU-NS），以及（b）通过常规喷雾干燥制备的用于持续释放的黏附剂Methocel™ F4M的5FU微粒（5FU-MS）。对这两种制剂的理化性质和空气动力学性质进行了体外评估，结果表明它们对肺部给药具有吸引力。所获得的理论空气动力学直径分别为0.322±0.07 µm（5FU-NS）和1.138±0.54 µm（5FU-MS）。可吸入颗粒分数（FR%）分别为76.84±0.07%（5FU-NS）和55.01±2.91%（5FU-MS）。体外黏附性能研究表明，在存在Methocel™ F4M的情况下具有显著的黏附效率。对5FU-MS和5FU-NS对黑色素瘤癌细胞（A2058和A375）的细胞毒性作用进行了测试，结果表明，在浓度分别低4.3倍和1.7倍时，二者均表现出与纯5FU相似的细胞毒性作用。
