Development of an Icariin-Loaded Bilosome-Melittin Formulation with Improved Anticancer Activity against Cancerous Pancreatic Cells

Abstract

Pancreatic cancer currently represents a severe issue for the entire world. Therefore, much effort has been made to develop an effective treatment against it. Emerging evidence has shown that icariin, a flavonoid glycoside, is an effective anti-pancreatic cancer drug. Melittin, as a natural active biomolecule, has also shown to possess anticancer activities. In the present study, with the aim to increase its effectiveness against cancerous cells, icariin-loaded bilosome-melittin (ICA-BM) was developed. For the selection of an optimized ICA-BM, an experimental design was implemented, which provided an optimized formulation with a particle size equal to 158.4 nm. After estimation of the release pattern, the anti-pancreatic cancer efficacy of this new formulation was evaluated. The MTT assay was employed for the determination of half maximal inhibitory concentration (IC50), providing smaller IC50 for ICA-BM (2.79 ± 0.2 µM) compared to blank-BM and ICA-Raw (free drug) against PNAC1, a human pancreatic cancer cell line isolated from a pancreatic carcinoma of ductal cell origin. Additionally, cell cycle analysis for ICA-BM demonstrated cell arrest at the S-phase and pre-G1 phase, which indicated a pro-apoptotic behavior of the new developed formulation. The pro-apoptotic and anti-proliferative activity of the optimized ICA-BM against PNAC1 cells was also demonstrated through annexin V staining as well as estimation of caspase-3 and p53 protein levels. It can be concluded that the optimized ICA-BM formulation significantly improved the efficacy of icariin against cancerous pancreatic cells.

Emerging Trends in Bilosomes as Therapeutic Drug Delivery Systems

“…A remarkable improvement in the cytotoxic activity of the compound 4e from PEGylated nanovesicle (IC 50 = 0.75 ± 0.03 µM) was found compared to the pure form (IC 50 = 2.11 ± 0.19 µM) [ 79 ]. In another study, Alhakamy et al [ 80 ] developed and evaluated icariin-loaded bilosomes-melittin (ICA-BM) in an attempt to increase the efficacy of these natural biomolecules against pancreatic cancer cells, PNAC1. The evaluation of pro-apoptotic protein levels, cell cycle analysis, and annexin V staining in PNAC1 cells demonstrated that the optimized ICA-BM formulation significantly augmented icariin’s efficacy in combating malignant pancreatic cells [ 80 ].…”

“…In another study, Alhakamy et al [ 80 ] developed and evaluated icariin-loaded bilosomes-melittin (ICA-BM) in an attempt to increase the efficacy of these natural biomolecules against pancreatic cancer cells, PNAC1. The evaluation of pro-apoptotic protein levels, cell cycle analysis, and annexin V staining in PNAC1 cells demonstrated that the optimized ICA-BM formulation significantly augmented icariin’s efficacy in combating malignant pancreatic cells [ 80 ]. Another study by the same research group evaluated piceatannol (PIC), an herbal polyphenolic compound with anti-cancercytotoxic activity, which was loaded into zein-modified bilosomes for treating lung cancer.…”

Icariin: A Promising Natural Product in Biomedicine and Tissue Engineering

“…ICRN (C 33 H 40 O 15 , M w = 676.67) is a type of prenylated flavonoid, showing extensive bioactivities such as antioxidant [ 44 , 45 , 46 , 47 ], neuroprotective [ 48 , 49 , 50 , 51 , 52 ], and antitumor [ 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ] behavior as well as anti-inflammatory responses [ 62 , 63 , 64 , 65 , 66 , 67 , 68 ], and can be used to treat erectile dysfunction [ 69 , 70 , 71 , 72 ]. It appears it can improve the function of organs including bones and the heart [ 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ].…”