title: In vitro uptake evaluation in Caco-2 cells and in vivo results in diabetic rats of insulin-loaded PLGA nanoparticles.
abstract: PLGA nanoparticles (NPs) are largely developed for biological applications but little is known about their uptake. Therefore, we focused our study on the modalities of insulin-loaded PLGA NPs transport across Caco-2 monolayers, and their hypoglycaemic effect on diabetic rats. Insulin-loaded PLGA NPs were formulated by a double emulsion solvent evaporation process. NPs mean diameter was between 130 and 180 nm. NPs were smooth and spherical with an entrapment efficiency above 80%. Fluorescently labeled NPs were incubated with Caco-2 cells to study the process of uptake and the intracellular fate by flow cytometry and confocal laser scanning microscopy. The kinetic of absorption was time-dependent and occurred by clathrin-mediated endocytosis. The intracellular traffic led to a basolateral exocytosis of NPs. In vitro studies and in vivo intraduodenal administration to diabetic rats showed that NPs were resistant in intestinal conditions long enough to allow both the intestinal absorption of NPs and the delivery of functional insulin in bloodstream. The resulting in vivo hypoglycaemic effect was similar to a long-acting insulin one. As no effect on glycaemia occurred after oral administration, further studies need to be conducted to protect NPs from the degradation occurring at the enteric level.
authors.affiliation: Centre Européen d'Etude du Diabète, Boulevard René Leriche, 67200 Strasbourg, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Reix
authors.forename: Audrey
authors.initials: A
authors.lastname: Parat
authors.forename: Elodie
authors.initials: E
authors.lastname: Seyfritz
authors.forename: Remmelt
authors.initials: R
authors.lastname: Van der Werf
authors.forename: Virginia
authors.initials: V
authors.lastname: Epure
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ebel
authors.forename: Louis
authors.initials: L
authors.lastname: Danicher
authors.forename: Eric
authors.initials: E
authors.lastname: Marchioni
authors.forename: Nathalie
authors.initials: N
authors.lastname: Jeandidier
authors.forename: Michel
authors.initials: M
authors.lastname: Pinget
authors.forename: Yves
authors.initials: Y
authors.lastname: Frère
authors.forename: Séverine
authors.initials: S
authors.lastname: Sigrist
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D018938:Caco-2 Cells; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D004337:Drug Carriers / Q000008:administration & dosage*; D004705:Endocytosis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid