A novel pH-sensitive liposome to trigger delivery of afatinib to cancer cells: Impact on lung cancer therapy

A novel drug delivery systems based on cationic (CL) and pH-sensitive liposomes (PSL) for tyrosine kinase inhibitor afatinib (AFT) were developed to enhance tumor-targetability against NSCLC cells and therapeutic effect. Optimal lipid to drug ratio was selected to prepare AFT-loaded PSL and CL with desirable physiochemical properties based on particle size, drug encapsulation efficiency (EE%), stability and release profiles. Moreover, antitumor activity was performed in vitro on human lung cancer cells (H-1975) using a WST-1 assay and Annexin-V apoptosis assay. The mean particle size of the liposomes was <100 nm, and EE% was >50% with lipid to drug ratio of 1:0.5. Stability data showed that PSL and CL were physically stable for 1 months at 4 and 25 °C. In vitro drug release study demonstrated the sustained release of AFT at pH 7.5; while PSL exhibited fast drug release in pH 5.5. This effect revealed that PSL showed pH-sensitive release behaviors. In addition, the in vitro cytotoxicity study was employed for AFT-loaded PSL due to optimal characterizations. Thus, in vitro anticancer activity revealed that AFT loaded-PSL triggered apoptosis in H-1975 cells. In addition, the inhibitory effect toward H-1975 and HCC-827 was observed, indicating, which indicated high antitumor activity of AFT-loaded PSL. Then, PSL might potentially create practical clinical strategies for better targetability and delivery of AFT for treatment of lung cancer.