Crystal Growth Centre, Anna University, Chennai, 600025, India.
National Centre for Nanoscience and Nanotechnology, University of Madras, Chennai, 600025, India.
Sci Rep. 2020 Mar 4;10(1):3991. doi: 10.1038/s41598-020-60888-5.
Drug resistance and damage caused to the normal cells are the drawbacks which have limited the use of the existing effective anticancer drugs. Attainment of a steady and extended release by encapsulating dual drugs into biocompatible and biodegradable vehicles is the key to enable the use of these drugs for effective inhibition of cancer. In this study, carboxymethyl chitosan (CMCS), a proficient water-soluble derivative of chitosan has been synthesized using chemical route and used for the delivery of 5-Fluorouracil and doxorubicin individually as well as in combination. Carboxymethylation occuring at -NH and OH sites of chitosan, has been confirmed using FTIR. EDX and Fluorescence studies elucidate the encapsulation of 5-Fluorouracil and doxorubicin into CMCS. The capability of CMCS to release the drugs in a more sustained and prolonged manner is evident from the obtained release profiles. About 14.9 µg/ml is enough to cause 50% cell death by creating oxidative stress and effectuating DNA fragmentation. Amidst the existing reports, the uniqueness of this work lies in using this rare coalition of drugs for the suppression of breast cancer and in reducing the side effects of drugs by encapsulating them into CMCS, which is evidenced by the high hemocompatibilty of the samples.
耐药性和对正常细胞的损伤是限制现有有效抗癌药物使用的缺点。通过将两种药物封装到生物相容性和可生物降解的载体中以实现稳定和延长释放，是使这些药物能够有效抑制癌症的关键。在这项研究中，羧甲基壳聚糖（CMCS）是壳聚糖的一种高效水溶性衍生物，通过化学途径合成，并用于单独和联合递送 5-氟尿嘧啶和阿霉素。壳聚糖的-NH 和-OH 位点发生的羧甲基化已通过 FTIR 得到证实。EDX 和荧光研究阐明了将 5-氟尿嘧啶和阿霉素包封到 CMCS 中。从获得的释放曲线可以明显看出，CMCS 具有以更持续和延长的方式释放药物的能力。通过产生氧化应激和导致 DNA 片段化，约 14.9μg/ml 的浓度就足以导致 50%的细胞死亡。在现有的报告中，这项工作的独特之处在于使用这种罕见的联合药物来抑制乳腺癌，并通过将它们封装到 CMCS 中减少药物的副作用，这可以从样品的高血液相容性得到证明。
