Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
Int J Biol Macromol. 2023 Jun 15;240:124396. doi: 10.1016/j.ijbiomac.2023.124396. Epub 2023 Apr 8.
Anti-cancer medications that are delivered specifically to the tumor site possess greater efficacy with less negative effects on the body. So, the current research relies on a novel method for intercalating the anticancer medication methotrexate in poly(3-hydroxybutyrate)/chitosan-graft poly (acrylic acid) conjugated with sodium hyaluronate. The graft copolymers were synthesized through persulfate-initiated grafting of acrylic acid onto a binary mixture of various amounts of chitosan and poly(3-hydroxybutyrate) (2/1, 1/1 and 1/2, w/w) using microwave irradiation. The graft copolymer was conjugated with sodium hyaluronate for targeted delivery of methotrexate drug specifically to colon cancer cell lines (Caco-2). The graft copolymers were characterized by many physical techniques. The maximum drug loading efficiency was observed in case of the graft copolymer/hyaluronate rich in chitosan content 69.7 ± 2.7 % (4.65 mg/g) with a sustained release about 98.6 ± 1.12 %, at pH 7.4. The findings of severe cytotoxicity having a value of the IC of 11.7 μg/ml, a substantial proportion of apoptotic cells (67.88 %), and an elevated level of DNA breakage inside the treated Caco-2 cells verified the effective release of methotrexate from the loaded copolymer matrix. Besides, the high stability and biological activity of the released drug was exhibited through occurrence of greater increment of reactive oxygen species and effect on the extent of expression of genes connected to apoptosis and anti-oxidant enzymes within the treated cells. Ultimately, this system can be recommended as potent carrier for methotrexate administration to targeted cancerous cells in the colon.
专门递送到肿瘤部位的抗癌药物具有更高的疗效，对身体的负面影响更小。因此，目前的研究依赖于一种将抗癌药物甲氨蝶呤插入聚（3-羟基丁酸酯）/壳聚糖-接枝聚（丙烯酸）与透明质酸钠缀合物中的新方法。接枝共聚物通过过硫酸盐引发丙烯酸接枝到不同量的壳聚糖和聚（3-羟基丁酸酯）（2/1、1/1 和 1/2，w/w）的二元混合物中，使用微波辐射合成。接枝共聚物与透明质酸钠缀合，用于将甲氨蝶呤药物靶向递送到结肠癌细胞系（Caco-2）。通过多种物理技术对接枝共聚物进行了表征。在富含壳聚糖的接枝共聚物/透明质酸钠中观察到最大的药物负载效率，其负载效率为 69.7±2.7%（4.65mg/g），在 pH 7.4 时具有约 98.6±1.12%的持续释放。在处理的 Caco-2 细胞中观察到严重细胞毒性，其 IC 值为 11.7μg/ml，大量凋亡细胞（67.88%）和 DNA 断裂水平升高，证实了甲氨蝶呤从负载共聚物基质中的有效释放。此外，通过处理细胞中与凋亡和抗氧化酶相关的基因表达程度的变化以及对活性氧产生的更大增加，表现出释放药物的高稳定性和生物活性。最终，该系统可被推荐为甲氨蝶呤在结肠靶向癌细胞给药的有效载体。
