Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
Interface Biologics Inc., Toronto, Ontario, Canada.
J Control Release. 2017 Mar 28;250:107-115. doi: 10.1016/j.jconrel.2017.02.008. Epub 2017 Feb 10.
An electrospun degradable polycarbonate urethane (PCNU) nanofiber scaffold loaded with antibiotic was investigated in terms of antibacterial efficacy and cell compatibility for potential use in gingival tissue engineering. Antimicrobial oligomer (AO), a compound which consists of two molecules of ciprofloxacin (CF) covalently bound via hydrolysable linkages to triethylene glycol (TEG), was incorporated via a one-step blend electrospinning process using a single solvent system at 7 and 15% w/w equivalent CF with respect to the PCNU. The oligomeric form of the drug was used to overcome the challenge of drug aggregation and burst release when antibiotics are incorporated as free drug. Electrospinning parameters were optimized to obtain scaffolds with similar alignment and fiber diameter to non-drug loaded fibers. AO that diffused from the fibers was hydrolysed to release CF slowly and in a linear manner over the duration of the study, whereas scaffolds with CF at the same concentration but in free form showed a burst release within 1h with no further release throughout the study duration. Human gingival fibroblast (HGF) adhesion and spreading was dependent on the concentration and form the CF was loaded (AO vs. free CF), which was attributed in part to differences in scaffold surface chemistry. Surface segregation of AO was quantified using surface-resolved X-ray photoelectron spectroscopy (XPS). These findings are encouraging and support further investigation for the use of AO as a means of attenuating the rapid release of drug loaded into nanofibers. The study also demonstrates through quantitative measures that drug additives have the potential to surface-locate without phase separating from the fibers, leading to fast dissolution and differential fibroblast cell attachment.
一种载有抗生素的可降解聚碳酸酯型聚氨酯（PCNU）纳米纤维支架的抗菌功效和细胞相容性进行了研究，该支架有望用于牙龈组织工程。抗菌低聚物（AO）由两个通过可水解键连接到三甘醇（TEG）的环丙沙星（CF）分子组成，通过一步共混静电纺丝工艺，在 7%和 15%w/w 相当于 PCNU 的 CF 浓度下，使用单一溶剂系统将其掺入。药物的低聚物形式被用来克服抗生素作为游离药物掺入时药物聚集和突释的挑战。对静电纺丝参数进行了优化，以获得与未载药纤维具有相似排列和纤维直径的支架。从纤维中扩散出来的 AO 会缓慢且线性地水解，释放出 CF，在整个研究过程中，而具有相同浓度但以游离形式存在的 CF 的支架在 1h 内突释，在整个研究过程中没有进一步释放。人牙龈成纤维细胞（HGF）的黏附和铺展取决于 CF 的浓度和加载形式（AO 与游离 CF），这部分归因于支架表面化学性质的差异。使用表面分辨 X 射线光电子能谱（XPS）对 AO 的表面分离进行了定量。这些发现令人鼓舞，支持进一步研究将 AO 用作减轻纳米纤维中载药快速释放的手段。该研究还通过定量测量表明，药物添加剂有可能在不与纤维相分离的情况下定位在表面，从而导致快速溶解和不同的成纤维细胞附着。
