PH-responsive double emulsion system for targeted anticancer therapy based on polyacrylic acid-polyvinyl pyrrolidone containing carbon nanotubes for 5-fluorouracil as an anticancer medication

Abstract

The second most significant cause of death among females is considered as breast cancer. Nowadays, many treatments are used to stop and control cancerous cells; among all, chemotherapy and anticancer medications have been applied to most patients for a long time. Although these methods successfully treat cancer, various harmful and unwanted side effects increase pain and suffering for the patients, including drug resistance, high toxicity, and non-targeting. Among different chemotherapy medications, 5-FU is one of the famous chemotherapeutic medications used to treat multiple tumors for over 70 years. With nanomaterials' help, intelligent drug delivery systems have been provided to carry different anticancer medications with minimal side effects. CNTs are well-known nanoparticles that could be used as carriers for smart drug delivery systems. Having an appropriate porosity, low toxicity, and transport, and regulating the amount of drug released make CNTs a suitable candidate as carriers in drug delivery systems. In this work, a combination of CNT nanoparticleswith PAA and PVP polymers was used to fabricate CNT/PAA/PVP nanocomposite as a drug delivery system, and 5-FU was encapsulated in the synthesized nanocarrier as an anticancer medication against MCF-7 breast cancer cell line with double emulsion technique (W-O-W). FT-IR and XRD analyses have been used to investigate different physical interactions and the crystalline behavior of the nanocomposite particles, respectively. DLS and Zeta potential identified nanoemulsions' average size distribution and surface charge. FESEM images were used to investigate the morphology features of the nanocarrier. The encapsulation and loading efficiency in CNT-PAA-PVP@5-FU nanocomposite was around 88.00 % and 45.5 %, respectively. The release pattern of 5-FU in the nanocomposite in the neutral and acidic conditions followed Korsmeyer-Peppas and Higuchi kinetic models, respectively. The pattern also proved that the release was pH-dependent and controlled in various media. MTT test verified a good cytotoxicity for the nanocomposite, and flow cytometry showed that the apoptotic percentage against MCF-7 in the nanocarrier was higher than free 5-FU. In light of these findings, the CNT-PAA-PVP@5-FU drug delivery system can be used to transport pharmaceuticals to cancerous tumors with fewer side effects compared to old treatments.