Optimization of nanoemulsion containing gemcitabine and evaluation of its cytotoxicity towards human fetal lung fibroblast (MRC5) and human lung carcinoma (A549) cells

• Published in: International journal of nanomedicine Vol. 14; pp. 7323 - 7338
• Main Authors: Wahgiman, Nadiatul Atiqah, Salim, Norazlinaliza, Abdul Rahman, Mohd Basyaruddin, Ashari, Siti Efliza
• Format: Journal Article
• Language: English
• Published: New Zealand Dove 01.01.2019; Dove Medical Press
• Subjects: A549 Cells; Analysis of Variance; Cell Death - drug effects; Cell Line; D-Optimal Mixture Design; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; Deoxycytidine - therapeutic use; Emulsions - chemistry; Fetus - cytology; Fibroblasts - cytology; Fibroblasts - drug effects; Gemcitabine; Humans; hydrophilic drug; Inhibitory Concentration 50; Kinetics; Lung - embryology; lung cancer; Lung Neoplasms - drug therapy; Nanoparticles - chemistry; Original Research; Particle Size; Phase Transition; Polysorbates - chemistry; Surface-Active Agents - chemistry; water-in-oil nanoemulsion; lung cancer; water-in-oil nanoemulsion; gemcitabine; D-optimal mixture design; hydrophilic drug
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S212635

Gemcitabine (GEM) is a chemotherapeutic agent, which is known to battle cancer but challenging due to its hydrophilic nature. Nanoemulsion is water-in-oil (W/O) nanoemulsion shows potential as a carrier system in delivering gemcitabine to the cancer cell. The behaviour of GEM in MCT/surfactants/NaCl systems was studied in the ternary system at different ratios of Tween 80 and Span 80. The system with surfactant ratio 3:7 of Tween 80 and Span 80 was chosen for further study on the preparation of nanoemulsion formulation due to the highest isotropic region. Based on the selected ternary phase diagram, a composition of F1 was chosen and used for optimization by using the D-optimal mixture design. The interaction variables between medium chain triglyceride (MCT), surfactant mixture Tween 80: Span 80 (ratio 3:7), 0.9 % sodium chloride solution and gemcitabine were evaluated towards particle size as a response. The results showed that NaCl solution and GEM gave more effects on particle size, polydispersity index and zeta potential of 141.57±0.05 nm, 0.168 and -37.10 mV, respectively. The optimized nanoemulsion showed good stability (no phase separation) against centrifugation test and storage at three different temperatures. The in vitro release of gemcitabine at different pH buffer solution was evaluated. The results showed the release of GEM in buffer pH 6.5 (45.19%) was higher than GEM in buffer pH 7.4 (13.62%). The cytotoxicity study showed that the optimized nanoemulsion containing GEM induced cytotoxicity towards A549 cell and at the same time reduced cytotoxicity towards MRC5 when compared to the control (GEM solution).