Efficacy potential of carboplatin encapsulated into Alginate-PAMAM dendrimer hybrid nanoparticles in 3D in vitro cell culture and in vivo experimental animal model
Project no. 21665 · Status: Kapanmış · 2020
Summary
<p>Carboplatin is a chemotherapeutic known as a second generation antineoplastic drug, and widely used for chemotherapy of lung, colon, breast, cervix, testicular and digestive system cancers. Although it is preferred over cisplatin due to its lower incidence of nephrotoxicity and ototoxicity, it is an agent with significantly less efficacy. For these reasons, in recent years, carboplatin-loaded nanoparticles as drug delivery systems have been synthesized in order to increase the uptake of carboplatin compounds in the tumor region and make them more effective. However, it has been stated that the drug loading efficiencies of these systems are still quite low. Therefore, achieving efficient carboplatin loading and targeted transport via nanoparticles remains a major challenge. In this study, EGF-conjugated carboplatin loaded alginate-PAMAM hybrid nanoparticles (EFG-CAP) were synthesized on a microfluidic platform. Their cytotoxicity and cellular drug uptake on lung cancer cells (A549) were studied in 2D and 3D in vitro cell culture. Anti-tumor activity was evaluated on an in vivo experimental animal model. At the end of the study, it was determined that the tumor tissue in the EFG-CAP group was greatly suppressed compared to the other groups, and this group had a reduction in tumor size. In addition, it has been demonstrated that EFG-CAP application induces apoptotic cell death. All these results showed that the tumor inhibition effect of EFG-CAP administration was much better than that of the Carboplatin or CAP administration groups alone.</p>