Department of Chemistry, Bogazici University, Bebek, Istanbul 34342, Turkey.
Boston University, Department of Biomedical Engineering, Boston, MA, USA.
Biomater Sci. 2023 Jan 31;11(3):813-821. doi: 10.1039/d2bm01199a.
Electrospun nanofibers are a 3D scaffold of choice for many drug delivery devices due to their high surface area, significant capacity for drug payload, ease of placement, and scalable manufacture. Herein, we report the synthesis of polymeric, pH-responsive nanofiber buttresses electrospinning. The homopolymer is comprised of an acrylic backbone with acid-sensitive, hydrolyzable, trimethoxybenzaldehyde-protected side chains that lead to buttress transformation from a hydrophobic to a hydrophilic state under physiologically relevant pH conditions (, extracellular tumor environment with pH = 6.5). Hydrolysis of the side chains leads to an increase in fiber diameter from approximately 350 to 900 nm and the release of the encapsulated drug cargo. drug release profiles demonstrate that significantly more drug is released at pH 5.5 compared to pH 7.4, thereby limiting the release to the target site, with docetaxel releasing over 20 days and doxorubicin over 7 days. Drug burst release, defined as >50% within 24 hours, does not occur at either pH or with either drug. Drug-loaded buttresses preserve drug activity and are cytotoxic to multiple human cancer lines, including breast and lung. Important to their potential application in surgical applications, the tensile strength of the buttresses is 6.3 kPa and, though weaker than commercially available buttresses, they provide sufficient flexibility and mechanical integrity to serve as buttressing materials the application with a conventional surgical cutting stapler.
静电纺丝纳米纤维因其高比表面积、对药物有效负载的高承载能力、易于放置和可扩展制造而成为许多药物输送装置的首选 3D 支架。在此,我们报告了聚合的 pH 响应纳米纤维支柱的合成 静电纺丝。均聚物由带有酸敏感、可水解的三甲氧基苯甲醛保护侧链的丙烯酸主链组成,在生理相关 pH 条件(、细胞外肿瘤环境 pH = 6.5)下,支柱从疏水性转变为亲水性状态。侧链的水解导致纤维直径从约 350nm 增加到 900nm,并释放出包裹的药物货物。药物释放曲线表明,在 pH 5.5 下释放的药物明显多于 pH 7.4,从而将释放限制在靶部位,多西他赛释放超过 20 天,阿霉素释放超过 7 天。药物突释,定义为 24 小时内超过 50%,在任一 pH 值下或使用任一药物都不会发生。负载药物的支柱保持药物活性,并对多种人类癌细胞系具有细胞毒性,包括乳腺癌和肺癌。对于它们在手术应用中的潜在应用很重要的是,支柱的拉伸强度为 6.3kPa,尽管比商业上可用的支柱弱,但它们具有足够的柔韧性和机械完整性,可以用作传统手术切割吻合器应用中的支柱材料。