## 1 Introduction  
Globally, diabetes is one of the most common metabolic diseases, affecting more than 345 million people worldwide [1]. It is estimated that in 2030, this number will increase to about 552 million,which is outrageous and a serious threat to public health [2]. Diabetes is broadly classified into two major groups, namely, Type 1, also known as insulin-dependent diabetes, which occurs when the body cannot produce enough insulin or when the pancreas is unable to produce sufficient insulin, causing hyperglycemia; and Type 2, a more common type of diabetes that results from the combination of inadequate insulin secretion and insulin resistance. In Type 1, the patient requires routine administration of insulin, being nowadays considered the most effective treatment with high specificity and activity [3]. Currently, the conventional route of insulin administration is subcutaneous, which faces many hurdles such as the difficulty of achieving a normal pattern of nutrient-related and basal insulin, significant tissue trauma and pain, particularly with multiple dosing, and hypoglycemia episodes [4]. In order to abrogate these challenges, it is of utmost importance to develop adequate oral insulin delivery systems for effective diabetes therapy. Indeed, oral ingestion remains the most desirable route for the application of pharmaceuticals, as it does not require a skilled health care professional and it therefore conveniently allows self-administration of the drug [5]. Oral ingestion of insulin would deliver the drug directly to the liver through portal circulation, mimicking the fate of endogenously secreted insulin [6]. However, oral delivery of many peptidic drugs faces important challenges. The high molecular weight and hydrophilic nature of many peptides limit their passive diffusion across the cell membrane, which forces them to pass through the gaps in the paracellular space (1-5 nm) [7]. Moreover, in the gastrointestinal tract (GIT), insulin absorption after oral administration is hampered by some pharmacokinetic challenges due to acidic gastric pH and the presence of digestive enzymes [3]. Insulin oral delivery has been investigated using some strategies to address these physicochemical problems by the use of colloidal systems such as microparticles (MPs), liposomes, nanoparticles, and microemulsions, just to mention a few [8]. Among these carriers, MPs have been proposed to overcome the pharmacokinetic problems associated with oral insulin delivery since they prevent peptide degradation in the acidic environment, prolong residence time, increase drug absorption, and promote controlled release, resulting in a better therapeutic response and patient compliance. MP delivery systems are usually formulated by encapsulation of the desired drug using a suitable inert polymeric carrier [9]. Within this context, a suitable biopolymer with uncoadhesive properties can be used as an enclosing carrier in MP preparation in order to enhance stability and achieve controlled release of, especially, some drugs that metabolize quickly. Mucoadhesiveness helps enhance closeness and prolong contact between drugs in polymeric carriers and their mucous surfaces, which maximizes the rate of drug absorption [10]. Such delivery systems confer significant advantages, particularly for drugs that are unstable in the GIT. In this context, we recently developed a polyethylene glycol (PEG)/mucin system for oral delivery of metformin hydrochloride, where PEG acts as an adhesion enhancer [11]. Regarding the other component of this system, mucins are a family of high-molecular-weight glycosylated proteins produced by epithelial tissues in most animals, being the major structure-forming component of the viscoelastic mucus [12; 13]. These glycoconjugates have gained increasing attention from researchers working on drug delivery as a biocompatible modifier for a variety of enzymes and proteins, enhancing their mucoadhesiveness [14; 15].