Afatinib-loaded Immunoliposomes Functionalized with Cetuximab: a Novel Strategy Targeting the Epidermal Growth Factor Receptor for Treatment of Non-small-cell Lung Cancer

Publication date: Available online 8 February 2019Source: International Journal of PharmaceuticsAuthor(s): Xiaoyan Lu, Sha Liu, Meishan Han, Xiucheng Yang, Kaoxiang Sun, Hongbo Wang, Hongjie Mu, Yuan Du, Aiping Wang, Ling Ni, Chunyan ZhangAbstractAfatinib, a selective and irreversible inhibitor of tyrosine kinase, was approved for the treatment of advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) overexpression in 2013. Cetuximab (CTX), an anti-EGFR monoclonal antibody, is co-administered with afatinib to improve efficacy. Unfortunately, dose-related adverse reactions caused by combination therapy have affected patient compliance, and have resulted in treatment discontinuation in severe cases. In the present study, afatinib was encapsulated in “liposomes” (LPs) to achieve longer circulation in the blood and an enhanced permeability-and-retention effect in tumors. Concomitantly, CTX was designed to bind to drug-loaded LPs to form “immuno-LPs” for tumor-cell selectivity and therapeutic activity. In vitro, the cellular internalization rate of immuno-LPs was significantly higher than that of LPs (p<0.05). In vivo, a markedly increased area under the curve and prolonged terminal half-life were detected in rats injected with the two LP formulations, indicating that LP encapsulation protected afatinib from binding to hemoglobin to control the risk of idiosyncratic drug reactions. Compared with free afatinib and LPs, immuno-LPs exhib...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research