Pancreatic cancer, a prominent cause of cancer-related deaths in both men and women, ranks among the top cancers associated with poor outcomes [1].

Pancreatic ductal adenocarcinoma (PDAC) is a type of pancreatic cancer that presents several therapeutic challenges for patients and healthcare providers. These challenges arise from the aggressive nature of the disease, late-stage diagnosis, and limited treatment options.

Late-stage diagnosis: PDAC is often diagnosed at an advanced stage, when the cancer has already spread and surgical intervention is less feasible. Early detection is challenging due to the lack of specific symptoms in the early stages, and by the time symptoms manifest, the cancer may have already progressed.

Surgical resection is the primary curative treatment for PDAC, but only a minority of patients are eligible for surgery due to late-stage diagnosis and tumor location. Additionally, even after successful surgery, the high rate of recurrence poses a significant challenge, especially because of resistance to chemotherapy and the lack of well-defined molecular targets, limiting the availability of targeted therapies.

The pancreatic tumor microenvironment is characterized by dense fibrosis and a lack of blood vessels, which hinders drug delivery. This makes it difficult for therapeutic agents to reach the tumor cells effectively, especially coupled with the lack of natural nutrients that may hinder the tumor growth [2].

Coenzyme Q10 (CoQ10) is a hydrophobic antioxidant found naturally, that plays a vital role in body energy production. Studies have demonstrated its anticancer effect in pancreatic cancer by enhancing ROS generation, along with antifibrotic properties [[3], [4], [5]]. However, CoQ10 has limited solubility in water. To enhance the cellular uptake of drugs, different strategies have been developed including increased interaction the with hydrophilic part of cellular phospholipid (using cell penetration peptides like TAT [6], ionic interaction of phosphate of membrane lipids [7,8]), increased interaction by hydrophobic part of cellular phospholipid (pro-drug [9]), and nanoparticulate drug delivery systems emerged by using one or two mechanisms above in the increasement cellular uptake over the past few decades [[10], [11], [12], [13]].

Saponins are a class of naturally occurring chemical compounds that are found in a wide variety of plants, including beans, legumes, and many medicinal herbs. These compounds exhibit molecular arrangement comprising a hydrophilic moiety, usually a sugar, and a hydrophobic entity, typically a triterpene or steroid. This amphiphilic structure allows saponins to interact with both water-soluble and lipid-soluble molecules [14]. Moreover, they have also been investigated for their potential anticancer properties, as they have shown different effects including cell-cycle arrest, antioxidant activity, cellular invasion inhibition, induction of apoptosis, and autophagy. Apoptosis in cancer cells [15]. Because of the amphiphilic properties, saponin can form micelles. The aim of this study is to investigate the feasibility of saponins as a micelle drug carrier for solubilization of CoQ10. Quillaja saponin, Ginsenoside R0, and Ginsenoside Rb1 are the three most known and used types of saponins. Quillaja saponin originates from the bark of the Quillaja Saponaria tree, which is native to Chile. Quillaja saponin is a complex mixture of triterpenoid saponins, that are characterized by their ability to form stable foams and emulsions in aqueous solutions [[16], [17], [18], [19]]. Extensive research has revealed its potential health benefits, including antimicrobial, antifungal, and antiviral properties, as well as anti-inflammatory effects [20].

Ginsenosides are a class of natural compounds found in the roots of the Panax ginseng plant, they are also known as panaxosides or saponins. Ginsenosides are triterpene saponins, meaning they consist of a triterpene molecule attached to one or more sugar molecules (arabinose, glucose and rhamnose etc.) and most of them have dammarane skeleton [21]. Ginsenoside Rb0 (Rb0) and Ginsenoside Rb1 (Rb1) are two types of bioactive compounds found in ginseng, a popular medicinal herb that has been used in traditional medicine for centuries [21]. In contrast, Rb0 is a less well-studied ginsenoside which is found in ginseng. It has been shown to have anti-inflammatory, antioxidant properties and has been studied for its potential to reduce the risk of certain types of cancer [[22], [23], [24]]. Rb1 is the most abundant and well-studied ginsenoside found in ginseng. It has been shown to have a variety of health benefits, including diabetes, anti-inflammatory, antioxidant, and neuroprotective properties [25]. There are limited studies about using these all saponins as a drug carrier [[26], [27], [28], [29]].

In this study, saponins are used as a micelle drug carrier because of their amphiphilic properties. The three most popular saponins that Quillaja saponin (Quill), Ginsenoside R0 (Rb0), and Ginsenoside Rb1 (Rb1) were to increase the targeted deliver of CoQ10 and CoQ10 micelles and to investigate their anti-cancer impact on human pancreas adenocarcinoma (PANC-1), human pancreatic microvascular endothelial cells (H6C7) and transgenics mice.