Progress in the Development of Chitosan Based Insulin Delivery Systems: A Systematic Literature Review

Abstract

Diabetes mellitus is a chronic disease that is considered a worldwide epidemic, and its control is a constant challenge for health systems. Since insulin had its first successful use, scientists have researched to improve the desired effects and reduce side-effects. Over the years, the challenge has been to increase adherence to treatment and improve the quality of life for diabetics by developing an insulin delivery system. This systematic review (SR) analyses experimental articles from 1998 to 2018 related to the development of the chitosan/insulin delivery system (CIDS). Automated support: Start tool was used to perform part of these activities. The search terms “insulin”, “delivery or release system”, and “chitosan” were used to retrieve articles in PubMed, Science Direct, Engineering Village, and HubMed. A total of 55 articles were selected. The overview, phase, model, way of administration, and the efficiency of CIDS were analyzed. According to SR results, most of the articles were published from 2010 onwards, representing 72.7% of the selected papers, and research groups from China publicized 23.6% of the selected articles. According to the SR, 51% of the studies were carried out in vivo and 45% in vitro. Most of the systems were nanoparticle based (54.8%), and oral administration was proposed by 60.0% of the selected articles. Only 36.4% performed loaded capacity and encapsulation efficiency assays, and 24 h (16.4%), 12 h (12.7%), and 6 h (11.0%) were the most frequent insulin release times. Chitosan’s intrinsic characteristics, which include biodegradability, biocompatibility, adhesiveness, the ability to open epithelial tight junctions to allow an increase in the paracellular transport of macromolecular drugs, such as insulin, and the fact that it does not result in allergic reactions in the human body after implantation, injection, topical application or ingestion, have contributed to the increase in research of CIDS over the years. However, the number of studies is still limited and the use of an alternative form of insulin administration is not yet possible. Thus, more studies in this area, aiming for the development of an insulin delivery system that can promote more adherence to the treatment and patient comfort, are required.

In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of Insulin

“…However, only a few studies reported the nasal delivery of insulin-loaded nanoparticles. It has been revealed that chitosan is able to dramatically enhance the nasal absorption of polar molecules, including peptides and proteins that otherwise are only poorly absorbed via the IN route [64]. Therefore, the effect of chitosan-coating on nanoparticle characteristics, mucoadhesion, drug release, cytotoxicity, and permeability was investigated in comparison with the uncoated nanoparticles.…”

Applications of Chitosan-Alginate-Based Nanoparticles—An Up-to-Date Review

“…Its biocompatibility, biodegradability, nontoxicity, mucoadhesivity, and hemocompatibility are ideal characteristics for designing nanocarriers with controlled delivery and sustained release of various therapeutics [10,[20][21][22][23][24][25][26][27]. Chitosan has shown great promise in nanodelivery for the treatment of cancer [28][29][30], diabetes [31][32][33], eye diseases [34][35][36], infectious diseases [37][38][39][40][41], and more, being also recently employed in the delivery of vaccines [42][43][44][45].…”

Critical material designs for mucus- and mucosa-penetrating oral insulin nanoparticle development

“…Successful mucus penetration requires nanoparticles to first initiate mucoadhesion at the outermost layer of the mucus barrier (Figure 1). Mucoadhesive platforms for oral insulin delivery have been designed using polymers such as thiomers, poly(lactic-co-glycolic acid), alginate, and chitosan [81][82][83][84]. However, the early mucoadhesive nanoparticulate carriers have failed to translate to high oral insulin bioavailability nor significant hypoglycaemic effect [85].…”