The effect of EGCG/tyrosol-loaded chitosan/lecithin nanoparticles on hyperglycemia and hepatic function in streptozotocin-induced diabetic mice

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia that arises from inadequate insulin secretion (type 1 diabetes) or inefficient insulin utilization (type 2 diabetes) [1]. Diabetes is a global health issue that affects 463 million adults aged 20–79 globally, as reported by the International Diabetes Federation (IDF) in 2019. If effective preventive measures and management strategies are not implemented, the number of people affected will reach 700 million by 2045 [2]. This staggering number highlights the urgent need for increased awareness, prevention, and management of this chronic disease. Treating diabetes, particularly Type 2 diabetes mellitus (T2DM), has been a major challenge for healthcare professionals worldwide. While conventional pharmacological interventions have shown some efficacy, there is an increasing interest in investigating alternative treatment options, particularly those derived from natural compounds [[3], [4], [5]]. Natural compounds are gaining attention as potential therapies with minimal side effects compared to synthetic drugs [[6], [7], [8]]. In this regard, epigallocatechin-3-gallate (EGCG) and tyrosol are natural compounds with well-documented antioxidant and anti-inflammatory properties [9]. EGCG (a catechin gallate ester) is a significant polyphenol compound found in green tea, and tyrosol (2-(4-hydroxyphenyl) ethanol) is a phenolic compound in numerous plant-based foods, like olives and olive oil [10]. Previous studies have shown their potential for facilitating T2DM by improving insulin sensitivity [11], reducing oxidative stress [12], and modulating inflammatory responses [13]. Nevertheless, the therapeutic efficacy of EGCG and tyrosol in T2DM management can be restricted by their low aqueous solubility and poor bioavailability [14]. To address this issue, encapsulating compounds in nanoparticles (NPs) may enhance drug release and increase their therapeutic potency [15,16].

The application of NPs has recently gained considerable importance in medicine [17]. The nanoparticle's application in drug delivery systems allows for controlled drug release, reduces systemic toxicity, and ensures sustained and targeted delivery [[18], [19], [20]]. With their small size and large surface area, NPs can encapsulate and protect therapeutic agents, enhancing their stability and bioavailability [21,22]. In the case of diabetes, NPs can encapsulate and transport insulin, allowing for non-invasive administration and overcoming limitations associated with injections [23]. Furthermore, NPs can be engineered to specifically target pancreatic cells or insulin receptors, improving therapeutic efficacy and minimizing off-target effects [24]. Overall, the application of NPs in diabetes treatment shows promise in revolutionizing drug delivery systems, promoting patient convenience, and enhancing treatment outcomes.

In this regard, chitosan/lecithin nanoparticles (C/L-NPs) offer unique advantages in drug delivery systems for the management of diabetes [25]. The unique properties of C/L-NPs in nanomedicine have sparked significant interest in their potential biomedical applications. These NPs have also been explored as drug-delivery systems in different biomedical fields, including cancer therapy, wound healing, and antibacterial activity [26]. Chitosan, a biocompatible and biodegradable polysaccharide derivative from crustacean shells [27], and lecithin, a phospholipid derived from soybean, can self-assemble to form NPs with high stability and controlled release characteristics. The C/L-NPs can be easily surface-modified to improve bioavailability and target specific cells or tissues. Additionally, they have demonstrated good biocompatibility, minimal toxicity, and the potential for encapsulation of both hydrophilic and hydrophobic drugs [28]. The application of C/L-NPs in nanomedicine holds promise for improved drug delivery, personalized medicine, and enhanced treatment outcomes in various disease conditions.

As a result, the current study aimed to prepare self-assembled C/L-NPs loaded with EGCG and tyrosol (EGCG/tyrosol-loaded C/L NPs) to overcome the limitations of free EGCG/tyrosol application in mice with streptozotocin (STZ)-induced T2DM. We believe that the unique combination of EGCG and tyrosol components in chitosan/lectin NPs has synergistic effects and could potentially be effective in treating diabetes. It is hypothesized that the combination of EGCG and tyrosol, delivered using C/L NPs, may exhibit enhanced antidiabetic effects compared to free drug administration. Furthermore, by encapsulating EGCG/tyrosol in C/L NPs, we can enhance their stability, solubility, and bioavailability, which has the potential to amplify their therapeutic benefits. This study can help to improve our understanding of nanomedicine-based strategies for T2DM management.

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