Jauković Valentina, Krajišnik Danina, Daković Aleksandra, Damjanović Ana, Krstić Jugoslav, Stojanović Jovica, Čalija Bojan
University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11 221 Belgrade, Serbia.
University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11 221 Belgrade, Serbia.
Mater Sci Eng C Mater Biol Appl. 2021 Apr;123:112029. doi: 10.1016/j.msec.2021.112029. Epub 2021 Mar 10.
The functionality of halloysite (Hal) nanotubes as drug carriers can be improved by lumen enlargement and polymer modification. This study investigates the influence of selective acid etching on Hal functionalization with cationic biopolymer chitosan. Hal was subjected to lumen etching under mild conditions, loaded under vacuum with nonsteroidal antiinflammatory drug aceclofenac, and incubated in an acidic solution of chitosan. The functionality of pristine and etched Hal before and upon polymer functionalization was assessed by ζ-potential measurements, structural characterization (FT-IR, DSC and XRPD analysis), cell viability assay, drug loading and drug release studies. Acid etching increased specific surface area, pore volume and pore size of Hal, decreased ζ-potential and facilitated binding of the cationic polymer. XRPD and DSC analysis revealed crystalline structure of etched Hal. Successful chitosan binding and drug entrapment were further confirmed by FT-IR and DSC studies. XRPD showed surface polymer binding. DSC and FT-IR analyses confirmed the presence of the entrapped drug in its crystalline form. Drug loading was increased for ≈81% by selective lumen etching. Slight decrease of drug content occurred during chitosan functionalization due to aceclofenac diffusion in the polymer solution. The drug release was more sustained from etched Hal nanocomposites (up to ≈87% for 12 h) than from pristine Hal (up to ≈97% for 12 h) due to more intensive chitosan binding. High human fibroblast survival rates upon exposure to pristine and etched Hal before and after chitosan functionalization (>90% in the concentration of 1000 μg/mL) confirmed that both lumen etching under mild conditions and polymer functionalization had no significant effect on cytocompatibility. Based on these findings, selective lumen etching in combination with polycation modification appears to be a promising approach for improvement of Hal nanotubes functionality by increasing payload, polymer binding capacity, and sustained release properties with no significant effect on their cytocompatibility.
通过扩大管腔和聚合物改性可以提高埃洛石（Hal）纳米管作为药物载体的功能。本研究调查了选择性酸蚀刻对阳离子生物聚合物壳聚糖对Hal功能化的影响。在温和条件下对Hal进行管腔蚀刻，在真空下负载非甾体抗炎药醋氯芬酸，并在壳聚糖酸性溶液中孵育。通过ζ电位测量、结构表征（傅里叶变换红外光谱、差示扫描量热法和X射线粉末衍射分析）、细胞活力测定、药物负载和药物释放研究来评估原始Hal和蚀刻后的Hal在聚合物功能化前后的功能。酸蚀刻增加了Hal的比表面积、孔体积和孔径，降低了ζ电位，并促进了阳离子聚合物的结合。X射线粉末衍射和差示扫描量热法分析揭示了蚀刻后Hal的晶体结构。傅里叶变换红外光谱和差示扫描量热法研究进一步证实了壳聚糖的成功结合和药物包封。X射线粉末衍射显示表面聚合物结合。差示扫描量热法和傅里叶变换红外光谱分析证实了包封药物以结晶形式存在。通过选择性管腔蚀刻，药物负载增加了约81%。由于醋氯芬酸在聚合物溶液中的扩散，在壳聚糖功能化过程中药物含量略有下降。由于壳聚糖结合更强烈，蚀刻后的Hal纳米复合材料的药物释放比原始Hal更持久（12小时内高达约87%）（原始Hal在12小时内高达约97%）。在壳聚糖功能化前后，暴露于原始Hal和蚀刻后的Hal时，人类成纤维细胞的高存活率（在1000μg/mL浓度下>90%）证实，温和条件下的管腔蚀刻和聚合物功能化对细胞相容性均无显著影响。基于这些发现，选择性管腔蚀刻与聚阳离子改性相结合似乎是一种有前途的方法，可通过增加载药量、聚合物结合能力和缓释性能来改善Hal纳米管的功能，而对其细胞相容性无显著影响。
