title: Synthesis and characterization of pH-responsive nanoscale hydrogels for oral delivery of hydrophobic therapeutics.
abstract: pH-responsive, polyanionic nanoscale hydrogels were developed for the oral delivery of hydrophobic therapeutics, such as common chemotherapeutic agents. Nanoscale hydrogels were designed to overcome physicochemical and biological barriers associated with oral delivery of hydrophobic therapeutics such as low solubility and poor permeability due to P-glycoprotein related drug efflux. Synthesis of these nanoscale materials was achieved by a robust photoemulsion polymerization method. By varying hydrophobic monomer components, four formulations were synthesized and screened for optimal physicochemical properties and in vitro biocompatibility. All of the responsive nanoscale hydrogels were capable of undergoing a pH-dependent transition in size. Depending on the selection of the hydrophobic monomer, the sizes of the nanoparticles vary widely from 120nm to about 500nm at pH 7.4. Polymer composition was verified using Fourier transform infrared spectroscopy and1H-nuclear magnetic resonance spectroscopy. Polymer biocompatibility was assessed in vitro with an intestinal epithelial cell model. All formulations were found to have no appreciable cytotoxicity, defined as greater than 80% viability after polymer incubation. We demonstrate that these nanoscale hydrogels possess desirable physicochemical properties and exhibit agreeable in vitro biocompatibility for oral delivery applications.
authors.affiliation: Department of Chemical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Amey S
authors.initials: AS
authors.lastname: Puranik
authors.affiliation: Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Ludovic P
authors.initials: LP
authors.lastname: Pao
authors.affiliation: Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: White
authors.affiliation: Department of Chemical Engineering, The University of Texas at Austin, Austin, TX 78712, USA; Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA; College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA; Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: peppas@che.utexas.edu.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Peppas
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000737:chemistry; D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007413:Intestinal Mucosa / Q000378:metabolism; D008027:Light; D008264:Macrophages / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D010539:Permeability; D000071228:Polyelectrolytes; D011108:Polymers / Q000737:chemistry; D012542:Scattering, Radiation; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D020100:Hydrogels; D000071228:Polyelectrolytes; D011108:Polymers; C513055:ABCB1 protein, human
keywords: Cancer; Hydrogels; Hydrophobic therapeutics; Nanoparticles; Oral drug delivery