Goreninskii Semen, Volokhova Apollinariya, Frolova Anastasia, Buldakov Mikhail, Cherdyntseva Nadezhda, Choynzonov Evgeny, Sudarev Evgeny, Filimonov Victor, Tverdokhlebov Sergei, Bolbasov Evgeny
Onconanotheranostics laboratory, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Science, Moscow, Russian Federation; B.P. Veinberg Research and Educational Center, Tomsk Polytechnic University, Tomsk, Russian Federation.
B.P. Veinberg Research and Educational Center, Tomsk Polytechnic University, Tomsk, Russian Federation; Department of Translational Cellular and Molecular Biomedicine, Chemical Faculty, National Research Tomsk State University, Russian Federation.
J Pharm Sci. 2023 Nov;112(11):2752-2755. doi: 10.1016/j.xphs.2023.08.025. Epub 2023 Sep 4.
Burst release, typical for the drug-loaded electrospun poly(ε-caprolactone) (PCL) scaffolds is unfavorable in case of cytostatics due to the toxic levels reached during the initial implantation period. In the present short communication, we report an unexpected ability of the composite scaffolds made of PCL and water-soluble polyvinylpyrrolidone (PVP) to provide long-term release of widely used anti-cancer drug doxorubicin hydrochloride (DOX-HCl). That effect was observed for electrospun DOX-HCl-loaded composite scaffolds based on PCL and PVP with various mass ratios (100/0, 95/5, 90/10, 75/25 and 50/50). After the morphology and water contact angle studies, it was concluded that PVP content has no effect on the average fiber diameter, while PVP content higher 10 wt. % changes the hydrophobic character of the scaffolds surface (water contact angle of 123.9 ± 3.5°) to superhydrophilic (water contact angle of 0°). Despite the dramatic change in water wettability, by high performance liquid chromatography (HPLC), it was revealed that the PVP content in the scaffolds reduces the DOX-HCl release rate under short (first hours) and long-term (during 1 month) exposure to phosphate buffer saline (PBS). These results are in good agreement with in vitro studies, in which the viability of HeLa cervical cancer cells was higher after 24 h of culture with scaffolds with high PVP content.
对于载药电纺聚己内酯(PCL)支架而言,突发释放是其典型特征。但对于细胞抑制剂来说,由于在初始植入期会达到有毒水平,这种突发释放是不利的。在本简短通讯中,我们报道了由PCL和水溶性聚乙烯吡咯烷酮(PVP)制成的复合支架具有意想不到的能力,能够实现广泛使用的抗癌药物盐酸多柔比星(DOX-HCl)的长期释放。基于PCL和PVP的不同质量比(100/0、95/5、90/10、75/25和50/50)的电纺载DOX-HCl复合支架都观察到了这种效果。在进行形态学和水接触角研究后得出结论,PVP含量对平均纤维直径没有影响,而PVP含量高于10 wt%会使支架表面的疏水特性(水接触角为123.9 ± 3.5°)转变为超亲水特性(水接触角为0°)。尽管水润湿性发生了显著变化,但通过高效液相色谱法(HPLC)发现,在短期(最初几小时)和长期(1个月内)暴露于磷酸盐缓冲盐水(PBS)的情况下,支架中的PVP含量会降低DOX-HCl的释放速率。这些结果与体外研究结果高度一致,在体外研究中,用高PVP含量的支架培养24小时后,HeLa宫颈癌细胞的活力更高。