Development and characterization of new insulin containing polysaccharide nanoparticles

Abstract

A nanoparticle insulin delivery system was prepared by complexation of dextran sulfate and chitosan in aqueous solution. Parameters of the formulation such as the final mass of polysaccharides, the mass ratio of the two polysaccharides, pH of polysaccharides solution, and insulin theorical loading were identified as the modulating factors of nanoparticle physical properties. Particles with a mean diameter of 500 nm and a zeta potential of approximately −15 mV were produced under optimal conditions of DS:chitosan mass ratio of 1.5:1 at pH 4.8. Nanoparticles showed spherical shape, uniform size and good shelf-life stability. Polysaccharides complexation was confirmed by differential scanning calorimetry and Fourier transformed infra-red spectroscopy. An association efficiency of 85% was obtained. Insulin release at pH below 5.2 was almost prevented up to 24 h and at pH 6.8 the release was characterized by a controlled profile. This suggests that release of insulin is ruled by a dissociation mechanism and DS/chitosan nanoparticles are pH-sensitive delivery systems. Furthermore, the released insulin entirely maintained its immunogenic bioactivity evaluated by ELISA, confirming that this new formulation shows promising properties towards the development of an oral delivery system for insulin.

Pullulan-based nanoparticles as carriers for transmucosal protein delivery

“…As can be observed in Figure 2, pullulan-based nanoparticles evidence similar structure and morphology, corresponding to spherical and compact nanoparticles. This morphology corresponds to that widely reported for many formulations of polysaccharide-based nanoparticles (Calvo et al, 1997b;Goycoolea et al, 2009;Oyarzun-Ampuero et al, 2009;Sarmento et al, 2006;TeijeiroOsorio et al, 2009;Zorzi et al, 2011).…”

Films based on chitosan polyelectrolyte complexes for skin drug delivery: Development and characterization

“…6 while Table 3 presents the endothermic and exothermic peaks detected and the values of enthalpies associated. Pure chitosan exhibits one endothermic peak at 112 • C associated to the evaporation of absorbed water, a glass transition at 243 • C and an exothermic peak at about 311 • C ascribed to the polymer degradation, including saccharide rings dehydration, depolymerization and decomposition of deacetylated and acetylated chitosan units [48,66]. These peaks have been reported in several other studies [26,67].…”

Oral Bioavailability of Insulin Contained in Polysaccharide Nanoparticles

“…Recently, we formulated insulin into DS/Chit nanoparticles, which fully retained insulin in simulated gastric medium, and sustained the release up to 24 h in simulated intestinal medium, while preserving its bioactivity. 26 The main objective of the present study was to determine whether insulin encapsulated in DS/Chit nanoparticles induced a hypoglycemic effect after oral administration to diabetic rats. The use of a single nanoparticle administration is the most common way of evaluating the oral insulin bioavailability, mostly because this assay is performed in fasted animals.…”