title: Effects of poly-(lactide-co-glycolide) nanoparticles on electrophysiological properties of enteroendocrine cells.
abstract: PLGA nanoparticles are widely used to deliver pharmacological compounds and genes to a variety of cell types. Despite the fact that many of these cells types depend critically on ion channel activity to function normally, there have been no studies on the effect of nanoparticles on the ion channel activity. To this end, we have investigated the effect of nanoparticles on cholecystokinin (CCK)-releasing enteroendocrine cell (EEC) line STC-1. It has been shown that regulation of CCK release from STC-1 cells in response to food depends on the normal electrogenic properties of these cells, including the activity of voltage-gated calcium and potassium channels. Due to the importance of voltage-gated ion channels in the normal physiological responses of STC-1 cells, we performed electrophysiological (patch clamp) experiments to assess the effects of PLGA nanoparticles on the voltage-gated calcium and potassium channels. Whole-cell patch clamp recordings on STC-1 cells containing 100 nm nanoparticles show no macroscopic differences in calcium and potassium channel activity. Additional experiments determined that the activation, inactivation, and use-dependent inactivation of these voltage-gated ion channels did not have any significant effect of nanoparticles on these basic biophysical properties. Lastly, we have examined the effects of PLGA nanoparticles on stimulus-induced rise in intracellular calcium concentration in STC-1 cells, which is necessary for release of CCK. Our data demonstrate that the use of PLGA nanoparticles did not alter the electrophysiological properties of STC-1 cells and supports the use of PLGA nanoparticles as an attractive option for delivering pharmaceuticals/genes to cells of the digestive system that might eventually prove useful for reducing appetite/food intake and in treatment of various gastrointestinal illnesses.
authors.affiliation: Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Bhavik
authors.initials: B
authors.lastname: Shah
authors.forename: Soujanya
authors.initials: S
authors.lastname: Kona
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Gilbertson
authors.forename: Kytai T
authors.initials: KT
authors.lastname: Nguyen
mesh_terms: D000818:Animals; D002460:Cell Line; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D019344:Lactic Acid / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid