title: Solid lipid nanoparticles formed by solvent-in-water emulsion-diffusion technique: development and influence on insulin stability.
abstract: Insulin-loaded solid lipid nanoparticles (SLN), obtained by the solvent-in-water emulsion-diffusion technique, were produced using isovaleric acid (IVA) as organic phase, glyceryl mono-stearate (GMS) as lipid, soy lecithin and sodium taurodeoxycholate (TDC) as emulsifiers. IVA, a partially water-miscible solvent with low toxicity, was used to dissolve both insulin and lipids. SLN of spherical shape were obtained by simple water dilution of the O/W emulsion. Analysis of SLN content after processing showed interesting encapsulation efficiency with respect to therapeutic doses; moreover, insulin did not undergo any chemical modification within the nanoparticles and most of it remained stable after incubation of the SLN with trypsin solution. The biological activity of insulin, i.e. the ability to decrease glycemia in rats, was not negatively influenced by the SLN production process, as after subcutaneous administration of insulin extracted from SLN to animals, the blood glucose levels were quite similar to those obtained after administration of a conventional insulin suspension. Consequently, SLN seem to have interesting possibilities as delivery systems for oral administration of insulin.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Torino, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Battaglia
authors.forename: Michele
authors.initials: M
authors.lastname: Trotta
authors.forename: Marina
authors.initials: M
authors.lastname: Gallarate
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: Carlotti
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Zara
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bargoni
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D012997:Solvents / Q000737:chemistry; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry*
chemical_list: D007328:Insulin; D008055:Lipids; D012997:Solvents; D014867:Water