Oral Bioavailability of Insulin Contained in Polysaccharide Nanoparticles

Abstract

The pharmacological activity of insulin-loaded dextran sulfate/chitosan nanoparticles was evaluated following oral dosage in diabetic rats. Nanoparticles were mucoadhesive and negatively charged with a mean size of 500 nm, suitable for uptake within the gastrointestinal tract. Insulin association efficiency was over 70% and was released in a pH-dependent manner under simulated gastrointestinal conditions. Orally delivered nanoparticles lowered basal serum glucose levels in diabetic rats around 35% with 50 and 100 IU/kg doses sustaining hypoglycemia over 24 h. Pharmacological availability was 5.6 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. Confocal microscopic examinations of FITC-labeled insulin nanoparticles showed adhesion to rat intestinal epithelium, and internalization of insulin within the intestinal mucosa. Encapsulation of insulin into dextran sulfate/chitosan nanoparticles was a key factor in the improvement of the bioavailability of its oral delivery over insulin solution.

Solubility and bioavailability of stabilized amorphous calcium carbonate

“…that died revealed damage to the esophagus or bladders on the stomach wall presumably caused by the metal syringe used in the administration procedure. Figures 5 and 6 present results from bioavailability experiments of rats that survived through the entire experiment, testing the fractional absorption of the preceding preparations intrinsically labeled with 45 Ca following a single oral administration. Figure 5 presents the changes in serum Ca concentration, as calculated by the radioactive readings normalized to the administered dose.…”

“…Three different radiolabeled preparations of calcium carbonate were synthesized using the intrinsic labeling method employing 1 mCi/mL of radioactive 45 CaCl 2 stock solution (PerkinElmer, supplied by Eisenberg Bros. Ltd., Airport City, Israel). Radiolabeled 45 CaCl 2 from the stock solution was diluted with CaCl 2 solution prepared for the calcium carbonate preparations to yield radioactivity of approximately 1 AE 0.3 mCi/5 mg of elemental calcium in each one of the preparations.…”

“…Radiolabeled 45 CaCl 2 from the stock solution was diluted with CaCl 2 solution prepared for the calcium carbonate preparations to yield radioactivity of approximately 1 AE 0.3 mCi/5 mg of elemental calcium in each one of the preparations. Syntheses of all three preparations from this point on were identical to the nonradioactive syntheses described under ''Materials and Methods'' for the synthesis of amorphous and crystalline calcium carbonate for analytical analysis.…”

“…(22) To date, reports on calcium bioavailability in both animals and humans have been inconclusive largely because small differences in experiment parameters can lead to significantly different results. (1,23,24) Taking this into account, evaluation of calcium bioavailability in the rat model is commonly performed using one of the following four assays: (1) analyzing secreted calcium in feces and urine (balance studies) following Ca 2þ administration, (25,26) (2) using double-isotope labeling techniques, such as used commonly with humans, despite suffering from technical difficulties and inaccurate results when performed in rats, (27,28) (3) multiple administrations of 45 Ca-labeled test meals throughout the duration of the experiment, (29) and (4) single administration of a 45 Ca-labeled preparation directly into the rat stomach by gavage. This last method was introduced in 1961 (30) and was found to be the most accurate and costeffective of the four.…”

“…This last method was introduced in 1961 (30) and was found to be the most accurate and costeffective of the four. (27) After careful review of these methods, we decided to use a single administration of 45 Ca-labeled material in this study, aimed at assessing Ca 2þ bioavailability when presented as the amorphous polymorph.…”