title: Physicochemical behavior and cytotoxic effects of p(methacrylic acid-g-ethylene glycol) nanospheres for oral delivery of proteins.
abstract: The challenges faced to orally deliver therapeutic agents with unfavorable physicochemical properties, such as proteins, have been the primary motivation for the design and development of novel oral delivery systems that could circumvent biological barriers. In this work, we examined complexation-sensitive hydrogel nanospheres composed of poly[methacrylic acid-grafted-poly(ethylene glycol)] (P(MAA-g-EG)), on a model biological environment. For this purpose, a gastrointestinal cell culture model, the Caco-2 cell line, was employed to investigate the cytotoxic effects of the polymeric carrier and its effects on the cell monolayer integrity. The determination of the cytotoxic effects of the polymer network on the cell monolayer was performed by a colorimetric assay and by the counting of viable cells using the trypan blue exclusion method. Electrophysiological measurements were performed to measure the transepithelial electrical resistance changes in the monolayers in the presence and absence of the nanosphere suspension. The examination of the physicochemical interactions of the P(MAA-g-EG) nanosphere system with Caco-2 cell monolayers revealed that these systems possessed low cytotoxicity and were capable of opening the tight junctions between epithelial cells, therefore significantly reducing the transepithelial electrical resistance.
authors.affiliation: NSF Program on Therapeutic and Diagnostic Devices, School of Chemical Engineering, Purdue University, West Lafayette, IN 47907-1283, USA.
authors.forename: Madeline
authors.initials: M
authors.lastname: Torres-Lugo
authors.forename: Marcos
authors.initials: M
authors.lastname: García
authors.forename: Rae
authors.initials: R
authors.lastname: Record
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Peppas
mesh_terms: D000284:Administration, Oral; D018938:Caco-2 Cells / Q000187:drug effects / Q000502:physiology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D016503:Drug Delivery Systems / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D036103:Nanotechnology / Q000379:methods* / Q000706:statistics & numerical data; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D011506:Proteins / Q000008:administration & dosage*
chemical_list: D011109:Polymethacrylic Acids; D011506:Proteins; C099679:poly(methacrylic acid-ethylene glycol); D011092:Polyethylene Glycols