title: Preparation, characterization, and transport of dexamethasone-loaded polymeric nanoparticles across a human placental in vitro model.
abstract: The purpose of this study was to prepare dexamethasone-loaded polymeric nanoparticles and evaluate their potential for transport across human placenta. Statistical modeling and factorial design was applied to investigate the influence of process parameters on the following nanoparticle characteristics: particle size, polydispersity index, zeta potential, and drug encapsulation efficiency. Dexamethasone and nanoparticle transport was subsequently investigated using the BeWo b30 cell line, an in vitro model of human placental trophoblast cells, which represent the rate-limiting barrier for maternal-fetal transfer. Encapsulation efficiency and drug transport were determined using a validated high performance liquid chromatography method. Nanoparticle morphology and drug encapsulation were further characterized by cryo-transmission electron microscopy and X-ray diffraction, respectively. Nanoparticles prepared from poly(lactic-co-glycolic acid) were spherical, with particle sizes ranging from 140 to 298 nm, and encapsulation efficiency ranging from 52 to 89%. Nanoencapsulation enhanced the apparent permeability of dexamethasone from the maternal compartment to the fetal compartment more than 10-fold in this model. Particle size was shown to be inversely correlated with drug and nanoparticle permeability, as confirmed with fluorescently labeled nanoparticles. These results highlight the feasibility of designing nanoparticles capable of delivering medication to the fetus, in particular, potential dexamethasone therapy for the prenatal treatment of congenital adrenal hyperplasia.
authors.affiliation: Department of Obstetrics & Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Hazem
authors.initials: H
authors.lastname: Ali
authors.forename: Irina
authors.initials: I
authors.lastname: Kalashnikova
authors.forename: Mark Andrew
authors.initials: MA
authors.lastname: White
authors.forename: Michael
authors.initials: M
authors.lastname: Sherman
authors.forename: Erik
authors.initials: E
authors.lastname: Rytting
mesh_terms: D001692:Biological Transport; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D003907:Dexamethasone / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D015233:Models, Statistical; D053758:Nanoparticles; D010316:Particle Size; D010539:Permeability; D010920:Placenta / Q000378:metabolism*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011247:Pregnancy; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone
keywords: BeWo cells; Congenital adrenal hyperplasia; Dexamethasone; Nanoparticles; Placenta; Pregnancy