NIOSOMES VERSUS PRONIOSOMES AS PROMISING DRUG DELIVERY SYSTEMS IN TREATMENT OF DIABETES MELLITUS Review Article MAHMOUD H. TEAIMA 1 , MOSTAFA I. GEBRIL 2 , FATHY I. ABD ALLAH 3,4 , MOHAMED A. EL-NABARAWI 1* 1 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt, 2 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt, 3 International Center for Bioavailability, Pharmaceutical and Clinical Research, Obour City 11828, Egypt, 4 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo 11651, Egypt Email: mahmoud.teaima@pharma.cu.edu.eg Received: 02 Jan 2022, Revised and Accepted: 30 Jul 2022 ABSTRACT Diabetes Mellitus (DM) has emerged as an epidemic that has affected millions of people globally in the last few decades. Conventional antidiabetic dosage forms have a lot of problems that necessitate searching for novel drug delivery systems to overcome these drawbacks. Niosomes and proniosomes have been used to carry a wide variety of antidiabetic drugs achieving controlled and sustained release, which improves patient compliance. This review article describes the fundamental aspects of niosomes and proniosomes, including their structural components, methods of preparation, advantages and drawbacks, characterization, factors affecting niosomes formation along with their application in the treatment of diabetes. It also highlights the participation of other drug delivery systems in the treatment of diabetes done, mainly in the last decade. Keywords: Diabetes mellitus (DM), Niosomes, Proniosomes, Ethosomes, Nanoparticles © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2022v14i5.44039. Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Diabetes Mellitus (DM) is a multi-factorial chronic pathological condition of elevated blood glucose level (BGL) caused by multiple genetic and/or environmental factors, more specifically due to either deficiency of secretion of insulin hormone or due to pancreatic β cells destruction. It may also be caused by the non- utilization of insulin due to insulin resistance (IR) [1, 2]. Diabetes mellitus (DM) is a major health issue, its prevalence presents a real threat to humans [3]. The possibility of diabetes varies in different ethnicities, such as black and Hispanic people, and some minorities, like American Indians and Natives of Alaska, are more likely to have diabetes for a specific genetic profile. Though a lot of antidiabetic drugs are present in the market, achieving a complete and successful cure for DM remains a problem as there are a lot of adverse effects associated with these medications like gastric irritation, phobia of injection, transient nausea, diarrhea, loss of appetite and many more. Also, frequent daily administration of conventional antidiabetic drugs leads finally to patient incompliance [4, 5]. Nanotechnology showed a promising role in the management of diabetes mellitus in the last few years. Vesicular drug delivery systems have gained wide attention in the field of nanotechnology. These systems have the potential to carry a variety of drugs and have been widely used for various goals such as drug targeting, controlled and sustained release, and enhancement of permeation for drugs with low permeability [6]. Nanotechnological systems overcome conventional dosage forms drawbacks such as low aqueous solubility, poor bioavailability, low membrane permeability, variable plasma concentration, undesirable effects, and of course, poor patient compliance because of multiple administration [7, 8]. Nanotechnological systems such as liposomes and niosomes can carry both hydrophilic and hydrophobic drug moieties by encapsulation and partitioning into hydrophobic and hydrophilic parts also act as drug reservoirs [9]. A lot of advantages, but some physical and chemical problems made liposomes unsuitable for oral administration, such as hydrolysis and degradation of phospholipids or problems associated with storage for a long time as aggregation, fusion or leakage, and oxidation in aqueous systems [10]. These drawbacks of liposomes opens the door for niosomes to make remarkable progress. From the last decade onwards, Niosomes and proniosomes are used to improve oral bioavailability of antidiabetic drugs. Searched keywords include niosomes, proniosomes and diabetes mellitus. Sources include recently published review articles and papers mainly published in the last ten years. This review attempts to provide all the basic details about niosomes and proniosomes that were published mainly in the last decade. It focuses mainly on preparation methods of both niosomes and proniosomes, factors affecting their formation, characterization, advantages, disadvantages, and their application in the treatment of diabetes as well as the new achievements in other drug delivery systems to improve the treatment of diabetes. The next trend is using other nano drug delivery systems to improve bioavailability of antidiabetic drugs much more. Types of diabetes mellitus (DM) It is important to determine the type of diabetes to choose the right therapy. American Diabetes Association (ADA) sets the following classification [11]:  Type 1 diabetes mellitus (T1DM) occurs due to autoimmune β- cell destruction, usually leading to absolute insulin deficiency.  Type 2 diabetes mellitus (T2DM) occurs due to a progressive loss of β-cell insulin secretion frequently on the background of insulin resistance.  Gestational diabetes mellitus (GDM) is diagnosed in the second or third trimester of pregnancy that was not overt before gestation.  Specific types of diabetes due to other causes e. g., monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young (MODY)), diseases of the exocrine pancreas (such as cystic fibrosis and pancreatitis), and drug or chemical-induced diabetes (such as with glucocorticoid use, in the treatment of HIV/AIDS, or after organ transplantation). The two main types are (T1DM) and (T2DM) [12]: International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 14, Issue 5, 2022