## 1 Introduction  
Diabetes mellitus (DM) is a type of metabolic disorder with a high level of blood glucose over a prolonged period of time. Diabetes is rapidly increasing in every single part of the world and is considered as one of the major risks to public health in the 21 st century. It is expected that the prevalence of the DM will affect 366 million people by 2030 globally [1; 2; 3], with 90% of cases being the type 2 form of the disease [4].  
International Diabetes Federation data indicate that nine countries across the Gulf Region have the highest adult diabetes population, including Oman (13.4%); United Arab Emirates (18.7%); Saudi Arabia (16.8%); Kuwait (14.6%); Mauritius (16.2%); Bahrain (15.4%); Tonga (13.4%); Malaysia (11.6%); and Reunion (15.3%) [5]. Saudi Arabia is a developing country that has a population of over 28 million [6], of which 25% has been diagnosed with DM [7]. In addition, an increase of 40-50% by 2020 is also predicted [8].  
The current oral antidiabetic agents have no significant effect on repairing the actual secretory function of the pancreatic islet cells, and are often limited by many side effects, including hypoglycemia, dizziness, and nausea during clinical treatment. As a result, symptoms of Type 2 diabetes mellitus (T2 DM) patients remain incompetently managed. Thus, there has been an extensive interest in recognizing or identifying newer therapeutics for treating T2 DM [9].  
The dipeptidyl peptidase-4 (DPP-4) inhibitors are a relatively new class of oral diabetes drugs available for the treatment of type 2 diabetes mellitus (T2 DM). Strategies for treatment include DPP-4 inhibition, as well as to raise circulating levels of the incretin hormones that are involved in decreasing blood glucose levels in the blood, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Sitagliptin (LC15-0444), a newly developed potent oral anti-hyperglycemia agent (anti-diabetic drug) DPP-4 inhibitor, was extensively studied in clinical trials to investigate the molecular interaction with sitagliptin and type 2 diabetes enzyme (DPP-4) [10]. It was approved by the Korea Food & Drug Administration (KFDA) in the year 2012. It is well known that the blood glucose-lowering effects are mediated by glucagon-like peptide 1 GLP-1 and the gastric inhibitory polypeptide (GIP) incretin hormones that are inactivated by DPP-4. Unfortunately, one of the primary weaknesses of using sitagliptin is its biological half-life of 3.6 h in rats, and it is eliminated rapidly. Due to the shorter half-life of sitagliptin, it is suggested that patients need to follow, strictly, the dosing interval, which requires sitagliptin to be administered in two doses of 50 mg per day [11; 12; 13].  
Albumin has excellent mucoadhesive and pH-sensitive properties with controlled drug release characteristics, and thus, has been used widely to increase the delivery of active drugs into multiple mucosal sites [14]. Mucoadhesive drug delivery system offers several benefits by targeting and localization of the dosage form at a specific site, including the minimization of fluctuations in drug concentrations in the plasma, and prolonged retention time at the site of drug absorption, and a strengthened contact of therapeutic agent with the mucosa to increase the drug concentration gradient and also prevent adverse effects. Therefore, absorption and subsequent bioavailability of drugs may be improved, and reducing dosage intervals results in better patient compliance [15; 16].  
The aim of this research is to optimize a mucoadhesive nanoparticle formulation for the delivery of sitagliptin nanoparticles, and evaluate the in vivo drug distribution and retention in rat gastrointestinal tract (GIT). This is the first mucoadhesive nanoparticle drug delivery system that was ever designed to increase the efficacy of the antidiabetic drug sitagliptin.