International Journal of Nanomedicine (Apr 2023)
Development of Curcumin and Piperine-Loaded Bio-Active Self-Nanoemulsifying Drugs and Investigation of Their Bioactivity in Zebrafish Embryos and Human Hematological Cancer Cell Lines
Abstract
Mohsin Kazi,1 Muhammad Farooq Khan,2 Fahd A Nasr,3 Mohammad Z Ahmed,3 Ali S Alqahtani,3 Meser M Ali,4 Mohammed S Aldughaim5 1Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia; 2Department of Zoology, College of Science, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia; 3Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia; 4Department of Neurosurgery, Henry Ford Health, Detroit, MI, 48202, USA; 5Research Center, King Fahad Medical City, Riyadh Second Health Cluster, Riyadh, 11525, Kingdom of Saudi ArabiaCorrespondence: Mohsin Kazi; Mohammed S Aldughaim, Email [email protected]; [email protected]: Curcumin (CUR) and piperine (PP) are bioactive compounds with prominent pharmacological activities that have been investigated for the treatment of various diseases. The aim of the present study is to develop Bio-SNEDDS for CUR and PP as a combined delivery system for cancer therapy.Methods: CUR and PP loaded Bio-SNEDDSs with varying compositions of bioactive lipid oils, surfactants, and cosolvents were prepared at room temperature. Bio-SNEDDSs were characterized using a Zetasizer Nano particle size analyzer and further examined by transmission electron microscopy (TEM) for morphology. The in vivo toxicity of the preparations of Bio-SNEDDS was investigated in wild-type zebrafish embryos and cytotoxicity in THP-1 (human leukemia monocytic cells), Jurkat (human T lymphocyte cells) and HUVEC (non-cancerous normal) cells.Results: Bio-SNEDDSs were successfully developed with black seed oil, Imwitor 988, Transcutol P and Cremophor RH40 at a ratio of 20/20/10/50 (%w/w). The droplet size, polydispersity index and zeta potential of the optimized Bio-SNEDDS were found to be 42.13 nm, 0.59, and − 19.30 mV, respectively. Bio-SNEDDS showed a spherical structure evident by TEM analysis. The results showed that Bio-SNEDDS did not induce toxicity in zebrafish embryos at concentrations between 0.40 and 30.00 μg/mL. In TG (fli1: EGFP) embryos treated with Bio-SNEDDS, there was no change in the blood vessel structure. The O-dianisidine staining of Bio-SNEDDS treated embryos at 48 h post-fertilization also showed a significant reduction in the number of blood cells compared to mock (DMSO 0.1% V/V) treated embryos. Bio-SNEDDS induced significant levels of cytotoxicity in the hematological cell lines THP-1 and Jurkat, while low toxicity in normal HUVEC cell lines was observed with IC50 values of 18.63± 0.23 μg/mL, 26.03 ± 1.5 μg/mL and 17.52 ± 0.22 μg/mL, respectively.Conclusion: Bio-SNEDDS exhibited enhanced anticancer activity and could thus be an important new pharmaceutical formulation to treat leukemia.Graphical Abstract: Keywords: curcumin, piperine, bioactive self-nanoemulsifying drug delivery systems, leukemia, combination therapy
