Alginate/Chitosan Nanoparticles are Effective for Oral Insulin Delivery

Abstract

Purpose. To evaluate the pharmacological activity of insulin-loaded alginate/chitosan nanoparticles following oral dosage in diabetic rats. Methods. Nanoparticles were prepared by ionotropic pre-gelation of an alginate core followed by chitosan polyelectrolyte complexation. In vivo activity was evaluated by measuring the decrease in blood glucose concentrations in streptozotocin induced, diabetic rats after oral administration and flourescein (FITC)-labelled insulin tracked by confocal microscopy. Results. Nanoparticles were negatively charged and had a mean size of 750 nm, suitable for uptake within the gastrointestinal tract due to their nanosize range and mucoadhesive properties. The insulin association efficiency was over 70% and insulin was released in a pH-dependent manner under simulated gastrointestinal conditions. Orally delivered nanoparticles lowered basal serum glucose levels by more than 40% with 50 and 100 IU/kg doses sustaining hypoglycemia for over 18 h. Pharmacological availability was 6.8 and 3.4% for the 50 and 100 IU/kg doses respectively, a significant increase over 1.6%, determined for oral insulin alone in solution and over other related studies at the same dose levels. Confocal microscopic examinations of FITC-labelled insulin nanoparticles showed clear adhesion to rat intestinal epithelium, and internalization of insulin within the intestinal mucosa. Conclusion. The results indicate that the encapsulation of insulin into mucoadhesive nanoparticles was a key factor in the improvement of its oral absorption and oral bioactivity.

Oral Bioavailability of Insulin Contained in Polysaccharide Nanoparticles

“…The hypoglycemic effect appeared more pronounced after 6 h for a dose of 50 IU/kg, but a faster onset was observed for a dose of 100 IU/kg. The values of cumulative hypoglycemic effect found for both groups treated with different insulin doses showed sustained lowering of the blood glucose levels, observed 8 h after administration up to 24 h. Both doses resulted in minimum blood glucose, around 70% of the initial value, after 14 h. Previously, alginate/chitosan nanoparticles administered at same insulin dose level 30 also reduced blood glucose levels to their minimum point after 14 h, but to just over 60% of the initial value. Nevertheless, the hypoglycemic effect was higher after 24 h for the DS/Chit nanoparticles and the PA found for both formulations were comparable, as confirmed from Table 2, reflecting similar relative cumulative reduction in glucose blood levels.…”

“…The adhesion of Chit at the site of insulin GI absorption may offer various advantages for its uptake. 18,19 Previous work with Chit coated alginate nanoparticles 20 and other Chit-based nanoparticles 2,21 demonstrated their potential to orally administer insulin, but those formulations also showed premature gastric insulin release, exposing insulin to undesired GI degradation.…”

Microparticulate polyelectrolyte complexes for gentamicin transport across intestinal epithelia

“…Since calcium ions bind the guluronic sequences strongly, in a highly cooperative way, a competition on the same carboxylic groups between calcium, weakly bound to alginate mannuronic residues, and the polycation CS at this highest concentration could be hypothesized. In any case, CS should be, presumably, localized in the outer layer of the microparticles owing to its low diffusivity through the alginate network, as reported by others (Tønnesen & Karlsen, 2002;Sarmento et al, 2007;Wittaya-Areekul et al, 2006).…”

Biopolymeric nanoparticles

“…Chitosan endows nanoparticles with positive surface charge, prolongs the contact time of the active ingredients with the epithelium and enhances absorption via the paracellular transport pathway through the tight junctions [102][103][104]. Alginate micro and nanoparticles can be easily obtained by inducing gelation with calcium ions [105,106].…”