Green Synthesis of Nanoparticles Using Plant Extracts A Promising Antidiabetic Agent

Introduction

Diabetes mellitus (DM) is a group of metabolic disorders in which the elevated glucose levels in the blood is observed for a long extent of time, and the prevalence of diabetes w'orldwide increases the high risk of heart diseases, chronic kidney diseases, stroke, foot ulcers, and damage to eyes (Ashw'ini and Mahalingam, 2015). Undesired effects associated with conventional antidiabetic drugs have led to the exploration of alternative remedies. Many medicinal plants are used worldwide for the treatment of diabetes, and some of them have been experimentally assessed. Medicinal plant metabolites are perceived to have lesser side effects and have good hypoglycaemic potential (Ashwini and Mahalingam, 2015; Hussain et al., 2016). Plant-based products show higher binding affinities for the specific receptor systems, and their bioactivity is often selective when compared to totally synthetic compounds. Globally, numerous plant species are documented for their ethnomedicinal use in the treatment and control of diabetes; however, only a few of them have been scientifically evaluated for their efficacy (Eddouks et al., 2002; Khan et al., 2012; Bilal et al., 2018). There exists immense anecdotal evidence on the efficacy of medicinal plants for the treatment and management of diabetes mellitus by indigenous people (Ernst, 1997; Grover et al., 2002; Aboa et al., 2008; Malviya et al., 2010; Keter and Mutiso, 2012; Moradi et al., 2018; Skalli et al., 2019).

The prevalence and severity of diabetes have invoked a resurgence of interests in bioprospecting medicinal plants for novel plant-based therapeutics with anti-hyper- glycaemic activities. Many plant extracts and their isolated bioactive compounds have demonstrated significant antidiabetic activity when assessed using different types of experimental methods, and in some cases they exhibited more potency than conventional drug compounds (Kooti et al., 2016). The main active constituents of medicinal plants with antidiabetic activity include glycosides, alkaloids, polysaccharides, galactomannan gum, steroids, guanidine, carbohydrates, terpenoids, peptidoglycan, hypoglycin, glycopeptides, amino acids and inorganic ions. These phytochemicals downregulate or upregulate various metabolic cascades that directly or indirectly affect the glucose level in the human body. Patel et al. (2012) reported that anti- hyperglycaemic effects of some medicinal plants are due to their ability to restore the function of pancreatic tissues by causing an increase in insulin production. Several authors have reviewed the potential of plant secondary metabolites in suppressing and controlling blood sugar to normal levels through diverse mechanisms. However, most of the phytotherapeutic constituents have restricted bioavailability and efficacy as a result of their insolubility.

Nanotechnology is an emerging field that is presently revolutionizing medical research because of its utilization of nanomaterials, which are more biocompatible than conventional therapeutics, thereby bringing noteworthy developments in the treatment and diagnosis of diseases. A nanoparticle (NP), which is in essence a solid colloidal particle, is commonly defined as a discrete entity with at least one dimension being 100 nm (Garcia et al., 2010). Nanoparticles (NPs) demonstrate improved properties by virtue of their morphological parameters such as structure, shape, sizes (1-100 nm) and other amenable functionalities, which can be modulated for increased biocompatibility (Rafique et al., 2017; Bagyalakshmi and Haritha., 2017; Min et al., 2015). They are generally classified into organic and inorganic NPs and can be further categorized into different types based on the size, morphology and physical and chemical attributes. Such categorizations include carbon-based, ceramic, metal, semiconductor, polymeric and lipid-based nanoparticles. Organic NPs are solid particles that are made up of carbon-based compounds (mainly lipids or polymeric) and range in diameter from 10 nm to 1 pm (Kumar and Lai, 2014: Rafique et al., 2017). Inorganic NPs cover a broad range of substances such as elemental metals, metal oxides as well as metal salts. They incorporate semiconductor NPs (zinc sulphide - ZnS, zinc oxide - ZnO), metallic NPs (copper - Cu, gold - Au, aluminium - Al, silver - Ag) and magnetic NPs (copper - Co, iron -Fe, nickel - Ni). They have been given relatively more attention, and metal nanoparticles such as gold, iron, zinc, silver and nanoparticulate metal oxides have been extensively evaluated for their use as drug delivery systems in biomedical applications (Alkaladi et al., 2014).

The use of antidiabetic medicinal plants in the biosynthesis has received substantial research focus as they are considered a valuable alternative to hazardous synthetic compounds.

Nanotechnology and Diabetes Management

Diabetes mellitus has been known for more than 2,000 years and is defined as a group of metabolic disorders characterized by a complete or a relative lack of insulin (Woldu and Lenjisa, 2014). The increase in the prevalence of DM is due to three influencing factors: ethnicity, lifestyle and age. Diabetes mellitus is a lifelong disease that is characterized by hyperglycaemia due to disordered metabolism of glucose (Madsen-Bouterse and Kowluru, 2008). The World Health Organization (WHO, 2016) estimates that over 170 million people worldwide are afflicted with this chronic condition, and it is projected that in the year 2030 this number will rise to over 360 million (Wild et al., 2004).

Table 2.1 shows types of diabetes and their brief description. Type II diabetes mellitus (T2DM) is more worrisome as it accounts for 90% of global diabetes mellitus cases (Badeggi et al., 2020). With T2DM, your body either resists the effects of insulin, which is a hormone that regulates the movement of sugar into your cells, or does not produce enough insulin to maintain normal glucose level (Badeggi et al., 2020). Lysy et al. (2016) reported that 425 million population of adults age between 20 and 79 suffered from diabetes. This is equivalent to 9.9% of the world’s population

TABLE 2.1

Brief Descriptions of the Types of Diabetes

(Renner et al., 2020). According to an estimate by Cho et al. (2018) and Badeggi et al. (2020), if this disease is not properly managed, it would drastically increase by 48% in 28 years. Even though drugs are available on the market, they are costly and continuous administration causes side effects such as heart failure, diarrhoea, damage to the liver, dropsy, weight gain, abdominal pain, flatulence, and hyperglycaemia, necessitating the need for more potent and newer remedies (Badeggi et al., 2020; Lorenzati, et al., 2010; Ahmad et al., 2018).

To date, painless and simpler routes for insulin administration are still in demand in controlling diabetes. Conventional drug delivery systems still have several limitations, including low' potency, improper ineffective dosage and limited specificity for the target (Souto et al., 2019). Nanotechnology, a field that involves nanostructures, nanoparticle design, nanomaterials and their applications in humans, is increasing in importance in diabetics research in the recent decade (Gupta, 2017). It has facilitated the development of novel glucose measurement and insulin delivery modalities, which hold the potential to dramatically improve quality of life for diabetics (DiSanto et al., 2015). Nanoparticle-based delivery systems have been proposed to overcome the enzymatic degradation in the stomach and therefore to improve permeation through the gastrointestinal tract, in order to improve oral insulin absorption (Wong et al., 2017).

Sharma et al. (2015) discussed the limitation and applications of nanoparticles in delivering insulin to the targeted organs or/and tissues. Nanotechnology is being used in non-invasive methods to engineer more effective vaccine and insulin delivery gene and cell therapies for type 1 diabetes (Veiseh et al., 2016). Veiseh et al. (2016) analysed the state of the approaches and discussed critical issues for their translation to clinical practice in managing diabetes wdth nanomedicine, more specifically their challenges and opportunities. Souto et al. (2019) have discussed different types of nanoparticles such as lipid nanoparticles and polymeric niosomes, dendrimers, liposomes, micelles, nano-emulsions and also drug nanosuspensions for improved delivery of different oral hypoglycaemic agents in comparison with conventional therapies. In both types of diabetes, it is necessary to ameliorate the symptoms of hyperglycaemia to reduce the rate of disease progression and its associated complications, or to manage the blood sugar level by using insulin (Souto et al., 2019; Neef and Miller, 2017; Ismail and Csoka, 2017).