Kouser Rabia, Vashist Arti, Zafaryab Md, Rizvi Moshahid A, Ahmad Sharif
Material Research Laboratory, Department of Chemistry and Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.
Department of Immunology, Center of Personalized Nanomedicine, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida 33199, United States.
ACS Omega. 2018 Nov 30;3(11):15809-15820. doi: 10.1021/acsomega.8b01691. Epub 2018 Nov 20.
Nanocomposite hydrogels have found a wide scope in regenerative medicine, tissue engineering, and smart drug delivery applications. The present study reports the formulations of biocompatible nanocomposite hydrogel films using carboxymethyl cellulose-hydroxyethyl cellulose-acrylonitrile-linseed oil polyol (CHAP) plain hydrogel and Na-montmorillonite (NaMMT) dispersed CHAP nanocomposite hydrogel films (NaCHAP) using solution blending technique. The structural, morphological, and mechanical properties of resultant nanocomposite hydrogel films were further investigated to analyze the effects of polyol and NaMMT on the characteristic properties. The synergistic effect of polyol and nanofillers on the mechanical strength and sustained drug-release behavior of the resultant hydrogel films was studied, which revealed that the increased cross-link density of hydrogels enhanced the elastic modulus (up to 99%) and improved the drug retention time (up to 72 h at both pHs 7.4 and 4.0). The release rate of cisplatin in nanocomposite hydrogel films was found to be higher in CHAP-1 (83 and 69%) and CHAP-3 (79 and 64%) than NaCHAP-3 (77 and 57%) and NaCHAP-4 (73 and 54%) at both pHs 4.0 and 7.4, respectively. These data confirmed that the release rate of cisplatin in nanocomposite hydrogel films was pH-responsive and increased with decrease of pH. All nanocomposite hydrogel films have exhibited excellent pH sensitivity under buffer solution of various pHs (1.0, 4.0, 7.4, and 9.0). The in vitro biocompatibility and cytotoxicity tests of these films were also conducted using 3-(4,5-dimethylthiazole-2-yl-2,5-diphenyl tetrazolium bromide) assay of human embryonic kidney (HEK-293) and human breast cancer (MCF-7) cell lines up to 48 h, which shows their biocompatible nature. However, cisplatin-loaded nanocomposite hydrogel films effectively inhibited the growth of human breast MCF-7 cancer cells. These studies suggested that the proposed nanocomposite hydrogel films have shown promising application in therapeutics, especially for anticancer-targeted drug delivery.
纳米复合水凝胶在再生医学、组织工程和智能药物递送应用中有着广泛的应用范围。本研究报告了使用羧甲基纤维素 - 羟乙基纤维素 - 丙烯腈 - 亚麻籽油多元醇（CHAP）普通水凝胶和钠基蒙脱石（NaMMT）分散的CHAP纳米复合水凝胶膜（NaCHAP）通过溶液共混技术制备生物相容性纳米复合水凝胶膜的配方。进一步研究了所得纳米复合水凝胶膜的结构、形态和力学性能，以分析多元醇和NaMMT对其特性的影响。研究了多元醇和纳米填料对所得水凝胶膜的机械强度和持续药物释放行为的协同作用，结果表明水凝胶交联密度的增加提高了弹性模量（高达99%）并延长了药物保留时间（在pH 7.4和4.0时均长达72小时）。在pH 4.0和7.4时，纳米复合水凝胶膜中顺铂的释放率在CHAP - 1（分别为83%和69%）和CHAP - 3（分别为79%和64%）中高于NaCHAP - 3（分别为77%和57%）和NaCHAP - 4（分别为73%和54%）。这些数据证实纳米复合水凝胶膜中顺铂的释放率具有pH响应性，且随pH降低而增加。所有纳米复合水凝胶膜在各种pH值（1.0、4.0、7.4和9.0）的缓冲溶液中均表现出优异的pH敏感性。还使用人胚肾（HEK - 293）和人乳腺癌（MCF - 7）细胞系的3 -（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基四氮唑溴盐测定法对这些膜进行了长达48小时的体外生物相容性和细胞毒性测试，结果显示了它们的生物相容性。然而，负载顺铂的纳米复合水凝胶膜有效地抑制了人乳腺癌MCF - 7细胞的生长。这些研究表明，所提出的纳米复合水凝胶膜在治疗学中显示出有前景的应用，特别是在抗癌靶向药物递送方面。
