Biki Gupta1, Bijay Kumar Poudel1, Shobha Regmi1, Shiva Pathak1, Hima Bindu Ruttala1, Milan Gautam1, Gyeong Jin An1, Jee-Heon Jeong1, Han-Gon Choi2, Chul Soon Yong3, Jong Oh Kim4. 1. College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan, 712-749, South Korea. 2. College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University,, 55, Hanyangdaehak-ro Sangnok-gu, Ansan, 426-791, South Korea. 3. College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan, 712-749, South Korea. csyong@yu.ac.kr. 4. College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan, 712-749, South Korea. jongohkim@yu.ac.kr.
Abstract
PURPOSE: Lung cancer is the leading cause of cancer-related deaths. The aim of this study was to design solid lipid core nanocapsules (SLCN) comprising a solid lipid core and a PEGylated polymeric corona for paclitaxel (PTX) and erlotinib (ERL) co-delivery to non-small cell lung cancer (NSCLC), and evaluate their physicochemical characteristics and in vitro activity in NCI-H23 cells. METHODS: PTX/ERL-SLCN were prepared by nanoprecipitation and sonication and physicochemically characterized by dynamic light scattering, transmission electron microscopy, differential scanning calorimetry, X-ray diffraction, and Fourier-transform infrared spectroscopy. In vitro release profiles at pH 7.4 and pH 5.0 were studied and analyzed. In vitro cytotoxicity and cellular uptake and apoptosis assays were performed in NCI-H23 cells. RESULTS: PTX/ERL-SLCN exhibited appropriately-sized spherical particles with a high payload. Both PTX and ERL showed pH-dependent and sustained release in vitro profiles. PTX/ERL-SLCN demonstrated concentration- and time-dependent uptake by NCI-H23 cells and caused dose-dependent cytotoxicity in the cells, which was remarkably greater than that of not only the free individual drugs but also the free drug cocktail. Moreover, well-defined early and late apoptosis were observed with clearly visible signs of apoptotic nuclei. CONCLUSION: PTX/ERL-SLCN could be employed as an optimal approach for combination chemotherapy of NSCLC.
PURPOSE: Lung cancer is the leading cause of cancer-related deaths. The aim of this study was to design solid lipid core nanocapsules (SLCN) comprising a solid lipid core and a PEGylated polymeric corona for paclitaxel (PTX) and erlotinib (ERL) co-delivery to non-small cell lung cancer (NSCLC), and evaluate their physicochemical characteristics and in vitro activity in NCI-H23 cells. METHODS:PTX/ERL-SLCN were prepared by nanoprecipitation and sonication and physicochemically characterized by dynamic light scattering, transmission electron microscopy, differential scanning calorimetry, X-ray diffraction, and Fourier-transform infrared spectroscopy. In vitro release profiles at pH 7.4 and pH 5.0 were studied and analyzed. In vitro cytotoxicity and cellular uptake and apoptosis assays were performed in NCI-H23 cells. RESULTS:PTX/ERL-SLCN exhibited appropriately-sized spherical particles with a high payload. Both PTX and ERL showed pH-dependent and sustained release in vitro profiles. PTX/ERL-SLCN demonstrated concentration- and time-dependent uptake by NCI-H23 cells and caused dose-dependent cytotoxicity in the cells, which was remarkably greater than that of not only the free individual drugs but also the free drug cocktail. Moreover, well-defined early and late apoptosis were observed with clearly visible signs of apoptotic nuclei. CONCLUSION:PTX/ERL-SLCN could be employed as an optimal approach for combination chemotherapy of NSCLC.