Delivery of Melittin Loaded Niosomes for Breast Cancer Treatment: an in-vitro and in-vivo Evaluation of Anti-cancer Effect

Abstract

BackgroundMelittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, Melittin and Melittin loaded niosome had been optimized and assessed the anticancer effect an In-Vitro on 4T1 and SKBR3 breast cell lines and In-Vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the Niosomes; different niosomal formulations of Melittin were prepared and characterized in terms of morphology, size, Polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with Melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of Melittin, and Melittin loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the genes expression. 35 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done.Results: This study showed Melittin loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The Melittin loaded niosome affect the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. Also enhanced the apoptosis rate and inhibitored cell migration, invasion in both cell lines compared to the Melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in Melittin loaded niosome. Renal and hepatic biomarker activity did not show a significant difference in Melittin loaded niosome and Melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups.Conclusions: Our study successfully declares that Melittin loaded niosome had more anti-cancer effects than free Melittin. This project has demonstrated that Niosomes are suitable vesicle carriers for Melittin, compare to free form.

Anticancer Activity of Bee Venom Components against Breast Cancer

“…Bee venom was administered to breast cancer cells in six studies [ 19 , 20 , 21 , 22 , 23 , 24 ], whereas melittin or processed melittin was administered to breast cancer cells in seven studies [ 20 , 21 , 22 , 25 , 26 , 27 , 28 ]. Among them, three studies compared the results of melittin and bee venom administration [ 20 , 21 , 22 ].…”

“…There was only one study on phospholipase A2 from bee venom [ 29 ]. All studies, except one, attempted to confirm the results according to the dose [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 28 , 29 ]. On the other hand, three studies confirmed the results according to the duration of administration [ 22 , 23 , 26 ] ( Table 1 ).…”

An Optimized and Well-Characterized Niosome-Based Nanocarrier for Letrozole: A Brand- New Hybrid Therapy for Breast Cancer

“…AFM samples were prepared by placing 5μl of diluted niosomes on 1cm 2 glass slides and left to dry at room temperature. Prepared samples were visualized with a Nanowizard II atomic force microscope (JPK Instruments, Berlin, Germany) with a low-stress silicon nitride cantilevers (AppNano, USA) using AC mode at 66k Hz scan [17,18] .…”

pH-Responsive, Adorned Nanoniosomes for Codelivery of Cisplatin and Epirubicin: Synergistic Treatment of Breast Cancer

“… 16 Niosomes are biocompatible bilayer structures formed by the self-organization of nonionic surfactants and cholesterol that can overcome drawbacks associated with liposomes such as poor biocompatibility, low chemical stability, short storage life, and difficult large-scale production. 17 , 18 Niosomes have gained much attention in drug delivery systems because of their unique properties, including exceptional biocompatibility, biodegradability, stability, nonimmunogenicity, and the ability to encapsulate both hydrophilic and hydrophobic drugs. 19 − 21 Although vesicular systems like niosomes have special potential in cancer drug delivery, they still suffer from short blood circulation time and fast elimination by the reticuloendothelial system (RES).…”