Endocrine Abstracts (2009) 20 P376

Insulin-loaded lipid nanospheres surfaced with polysaccharides for oral delivery

Eliana B Souto1 & Selma B Souto2

1Faculty of Health Sciences, Universidade Fernando Pessoa, Porto, Portugal; 2Endocrinology Department, Hospital S João, Porto, Portugal.

Insulin delivery through oral route requires protein protection against gastric environment followed by intestinal absorption. Several approaches using colloidal carriers have been proposed to achieve such attempts. Examples are nanoparticles produced from lipid materials (mono, di and triacylglycerols, waxes, fatty acids), polymeric materials (poly acid lactic/glycolic co-polymers, poly-epsilon caprolactone) or from polysaccharides (hyaluronic acid, dextran sulphate, alginate, chitosan). The present work proposes a new drug delivery system composed of cetyl palmitate nanospheres as matrix core, reinforced with polysaccharide molecules for oral insulin administration. Mean particle size, swelling behaviour and protein release profiles in simulated gastrointestinal conditions have been assessed. Increased insulin protection and modified release profile from lipid nanospheres was observed by reinforcing their matrix with alginate-chitosan and/or dextran sulphate. Surfacing the nanospheres with polysaccharide molecules could avoid insulin release at pH 1.5, protecting the protein from the acidic environment and reducing the total insulin released at pH 6.5. This effect was explained by an interaction between the permanent negatively charged groups of dextran sulphate and insulin molecules. For oral protein absorption, the ileum seems to be an ideal site for nanosphere uptake, where abundant Peyer patches exist with proteolytic enzyme activity. The paracellular pathway has also been shown to contribute to protein absorption, most polypeptide drugs diffuse through the aqueous-filled tight junctional pathway due to their hydrophilic nature.

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