Insulin-loaded mucoadhesive nanoparticles based on mucin-chitosan complexes for oral delivery and diabetes treatment

Abstract

In this study, insulin-loaded nanoparticles (NPs) were prepared via self-gelation method using chitosan and aqueous soluble snail mucin as natural polymers. Herein, mucins were ionically interacted with chitosan at different concentrations to obtained insulin-loaded NPs, labelled as A1 (1:1) (i.e., chitosan 2 % w/v + mucin 2 % w/v) and A2 (2:1) (chitosan 4 % w/v + mucin 2 % w/v), using poloxamer and poly vinyl alcohol as solid surfactant. Such formulation was selected to provide the necessary dynamics for the formation of the nanoparticles while maintaining the surface properties that will favor the encapsulation of insulin. Each system was characterized in terms of their particle size distribution, morphology, zeta potential, and polydispersity index. In vitro release of insulin was evaluated in acidic solution (pH 1.2) and phosphate buffer solution (pH 7.4), and the hypoglycaemic activity was evaluated in diabetes rats. The prepared insulin-loaded NPs displayed particles with relatively smooth surfaces and an average particle size of 479.6 and 504.1 nm for A1 and A2, respectively. Zeta potential and polydispersity index, ranged from 22.1-31.2 mV and 0.155-0.185, respectively. The encapsulating efficiency for the systems A1 and A2 were 88.6 and 92.5, respectively, and a self-sustained release of encapsulated insulin was observed for over a period of 8 h. In vivo studies revealed a pronounced hypoglycaemic effect in diabetic rats after peroral administration of the insulin-loaded NPs compared to the effect caused by free oral insulin solution. In addition, both the pharmacokinetic and toxicity results showed low plasma clearance of insulin and no signs of toxicity on the liver enzyme and cell viability, which suggested good biocompatibility of the NPs formulations. Overall, the formation of NPs of insulin with chitosan and snail mucin represents a potentially safe and promising approach to protect insulin and enhance its peroral delivery.

Gels for constant and smart delivery of insulin

“…Unlike micelles, many are particles that are not self-assembling and, apart from size, have more in common with both minigels and microparticles. The composition varies from natural polymers such as chitosan, alginate, dextran, hyaluronic acid and other polysaccharides, [33][34][35][36] but also includes synthetically altered chitosan such as carboxylated, trimethylated (TMC), ethyl (DMEC), mucin-complexed, 37 carboxymethyl (CMCS), oleic acid-zinc insulin complexed, 38 thiolated chitosan 39 and vitamin B12-conjugated chitosan (VitB12-Chi) among many others. Chaturvedi et al included a complex multicomponent particle designed to optimise gut absorption.…”

Nanoparticles prepared from pterostilbene reduce blood glucose and improve diabetes complications

“…Moreover, the EE and LC exhibited little fluctuation and remained stable. However, the EE of insulin NPs prepared with chitosan and water-soluble snail mucin by Mumuni MA [ 41 ] et al was 88.6%. Chen [ 42 ] prepared spherical NPs from six-armed star-shaped poly(lactide-co-glycolide)(6-s-PLGA) NPs that were used to encapsulate puerarin (PU-NPs).…”

Nanoparticles Prepared From Pterostilbene (PTE): A New Strategy for Reducing Blood Glucose and Improving Diabetic Complications

“…Moreover, it can be seen that the EE and LC uctuate little and are stable. However, the EE of insulin NPs prepared by MumuniMA [43] et al with chitosan and water-soluble snail mucin is 88.6%. Chen [44] prepared spherical NPs from six-armed starshaped poly(lactide-co-glycolide)(6-s-PLGA) NPs that were used to encapsulate puerarin (PU-NPs).…”