## 1 Introduction  
Diabetes mellitus (DM) is a major public health problem that represents, nowadays, an important concern due to its increasing prevalence and due to the challenges related to itreatment, which is one of the major causes of mortality [1]. The specific symptom of this chronic metabolic disorder is hyperglycemia due to a deficiency in insulin secretion, caused by damaged pancreatic beta-cells, or, peripherally, insulin resistance, or both of them [2]. DM is associated with severe micro- and macro vascular complications, such as retinopathy [3; 4], neuropathy, nephropathy [5; 6], diabetic foot [7], atherosclerosis, myocardial infarction and stroke [8; 9], rheumatoid arthritis, renal failure, and neurodegenerative disorders [6]. Conventional antidiabetic drugs include sulfonylureas, biganides, thiazoltionedes, alpha-glucosidase inhibitors, glinides, andmodulators of incretins (glucagon-like peptide-1 receptor-agonists and dipeptidyl peptidase IV enzyme inhibitors) [10; 11]. The major target of antidiabetic therapy is to reduce the increased blood glucose level, which, in several cases, is very difficult to achieve [12]. In addition, many antidiabetic drugs are responsible for different side effects, such as hypoglycemia, liver and kidney injury, weight gain, gastrointestinal disturbances, and hypersensitivity reactions [13; 14]. Glibenclamide (Gly) is a second-generation sulfonylurea, which is frequently prescribed for diabetes mellitus type 2 (DM2), when the treatment with biganides and first-generation sulfonylureas cannot ensurean optimal glycemic control [13; 14]. It acts mainly bystimulating insulin secretion in pancreatic beta-cells and, consequently, by reducing the blood glucose levels [9; 10]. Despite its intense and long-term action, Gly has poor aqueous solubility, which causes reduced and variable oral bioavailability [15; 16]. The chronic hyperglycemia, which is the major cause of diabetes mellitus complications, promotes, also, oxidative stress through free reactive oxygen species (ROS) generation and suppression of antioxidant defense system [17; 18]. In addition, there is some evidence thatinvolves ROS in impaired beta-cells function caused by proinflammatory cytokines and autoimmune reactions [19]. Based on the implication of oxidative stress in the progression of diabetes mellitus and its complications, several antioxidants were evaluated for their beneficial effects [20]. Common antioxidants include vitamins (A, C, and E), glutathione, enzymes (superoxide dismutase, catalase, glutathione reductase), lipoic acid, coenzyme Q10, cofactors (folic acid, vitamins B1, B2, B6, B12), and minerals (copper, zinc, selenium, and manganese) [18; 21]. For lipoic acid (LA), literature data reveals important pharmacological effects, such as antioxidant [21; 22], antitumor and anti-inflammatory activity [23], as well as increasing the insulin sensitivity [24]. Moreover, LA is frequently used for relieving the diabetic neuropathy symptoms [25]. This, despite there are available different classes of oral antidiabetic drugs, with different mechanisms of action--new, safer, and effective agents are needed.Moreover, in recent years, many studies focused on the development of drug delivery systems with controlled or sustained release, in order to improve the pharmacokinetic profile of conventional drugs or to assure a safety profile [26; 27]. Chitosan (CS) is a natural biopolymer obtained by alkaline deacetylation of chitin, whose chemical structure consists in \(\beta\)-1,4-linked D-glucosamine and N-acetyl-D-glucosamine units [28]. It is biodegradable, biocompatible, non-toxic, has low immunogenicity [28; 29], and could be derivatized at the amino groups [30]. In addition, CS is known to have significant biological effects such as antidiabetic, antioxidant, antitumor, antimicrobial, anti-inflammatory, cholesterol lowering properties [30; 31].