Advanced Materials Research Laboratory, Department of Chemistry, Periyar University, Salem, Tamil Nadu, India.
Int J Pharm. 2013 Sep 10;453(2):514-22. doi: 10.1016/j.ijpharm.2013.06.030. Epub 2013 Jun 21.
This study examines the performance of novel hyaluronidase enzyme core-5-fluorouracil-loaded chitosan-polyethylene glycol-gelatin polymer nanocomposites, which were prepared using an ionic gelation technique, as targeted and controlled drug delivery vehicles. These hyaluronidase-loaded nanoparticles have recently been proposed as targeted and controlled drug delivery vehicle systems to tissues due to their ability to loosen the intercellular connective matrix of hyaluronic acid. The encapsulation efficiency and loading capacities of the nanoparticles demonstrated that these nanocomposites displayed sufficient binding ability, which depends on the pH and initial concentration of the drug. The cytotoxic effects of the chitosan-hyaluronidase-5-fluorouracil (CS-HYL-5-FU), chitosan-hyaluronidase-5-fluorouracil polyethylene glycol (CS-HYL-5-FU-PEG), and chitosan-hyaluronidase-5-fluorouracil polyethylene glycol-gelatin (CS-HYL-5-FU-PEG-G) nanoparticles were assessed using MTT assays, and the nanovectors were found to be less cytotoxic than the chemotherapeutic 5-FU after incubation for 3-12h. The particle sizes of the CS-HYL-5-FU, CS-HYL-5-FU-PEG and CS-HYL-5-FU-PEG-G polymer composites were between 300 and 580 nm, as determined by a Zetasizer. Scanning electron microscopy (SEM) analysis indicated that the nanocomposites exhibit a clear, smooth surface and fine morphology. Linkages of the polymers, enzyme, and drug were confirmed by FTIR spectroscopy. Atomic fluorescence microscopy (AFM) analysis confirmed the size of the polymer composite nanoparticles. Therefore, this work established that the drug can be successfully encapsulated in chitosan-polyethylene glycol-gelatin-accompanied hyaluronidase nanoparticles with a homogeneous distribution. These nanoparticles can be potential carriers for targeted and controlled drug delivery to cancer cells.
本研究考察了新型透明质酸酶核心-5-氟尿嘧啶负载壳聚糖-聚乙二醇-明胶聚合物纳米复合材料的性能，该材料是通过离子凝胶技术制备的，可用作靶向和控制药物传递载体。由于这些透明质酸酶负载的纳米颗粒能够松解透明质酸的细胞间连接基质，因此最近被提议作为靶向和控制药物传递载体系统用于组织。纳米颗粒的包封效率和载药量表明，这些纳米复合材料表现出足够的结合能力，这取决于药物的 pH 值和初始浓度。通过 MTT 分析评估了壳聚糖-透明质酸酶-5-氟尿嘧啶（CS-HYL-5-FU）、壳聚糖-透明质酸酶-5-氟尿嘧啶-聚乙二醇（CS-HYL-5-FU-PEG）和壳聚糖-透明质酸酶-5-氟尿嘧啶-聚乙二醇-明胶（CS-HYL-5-FU-PEG-G）纳米粒子的细胞毒性作用，发现与孵育 3-12 小时后的化疗药物 5-FU 相比，这些纳米载体的细胞毒性较小。通过 Zetasizer 测定，CS-HYL-5-FU、CS-HYL-5-FU-PEG 和 CS-HYL-5-FU-PEG-G 聚合物复合材料的粒径在 300nm 至 580nm 之间。扫描电子显微镜（SEM）分析表明，纳米复合材料具有清晰、光滑的表面和精细的形态。傅里叶变换红外光谱（FTIR）光谱证实了聚合物、酶和药物的连接。原子荧光显微镜（AFM）分析证实了聚合物复合纳米颗粒的大小。因此，本工作表明，药物可以成功地封装在壳聚糖-聚乙二醇-明胶伴随透明质酸酶纳米颗粒中，且分布均匀。这些纳米颗粒可能是癌症细胞靶向和控制药物传递的潜在载体。
