Development of a P((MAA-co-NVP)-g-EG) Hydrogel Platform for Oral Protein Delivery: Effects of Hydrogel Composition on Environmental Response and Protein Partitioning.
Hydrogels based upon terpolymers of methacrylic acid, N-vinyl pyrrolidone, and poly(ethylene glycol) are developed and characterized for their ability to respond to changes in environmental pH and to partition protein therapeutics of varying molecular weights and isoelectric points. P((MAA-co-NVP)-g-EG) hydrogels are synthesized with PEG-based cross-linking agents of varying length and incorporation densities. The composition is confirmed using FT-IR spectroscopy and shows peak shifts indicating hydrogen bonding. Scanning electron microscopy reveals microparticles with an irregular, planar morphology. The pH-responsive behavior of the hydrogels is confirmed under equilibrium and dynamic conditions, with the hydrogel collapsed at acidic pH and swollen at neutral pH. The ability of the hydrogels to partition model protein therapeutics at varying pH and ionic strength is evaluated using three model proteins: insulin, porcine growth hormone, and ovalbumin. Finally, the microparticles are evaluated for adverse interactions with two model intestinal cell lines and show minimal cytotoxicity at concentrations below 5 mg mL-1.
Department of Biomedical Engineering, The University of Texas at Austin, 107 West Dean Keeton Street Stop C0800, Austin, TX, 78712, USA.|Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, 107 West Dean Keeton Street Stop C0800, Austin, TX, 78712, USA.
Stephanie
S
Steichen
Department of Biomedical Engineering, The University of Texas at Austin, 107 West Dean Keeton Street Stop C0800, Austin, TX, 78712, USA.|Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, 107 West Dean Keeton Street Stop C0800, Austin, TX, 78712, USA.
Colleen
C
O'Connor
Department of Biomedical Engineering, The University of Texas at Austin, 107 West Dean Keeton Street Stop C0800, Austin, TX, 78712, USA.|Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, 107 West Dean Keeton Street Stop C0800, Austin, TX, 78712, USA.|McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 East Dean Keeton Street Stop C0400, Austin, TX, 78712, USA.|Department of Surgery and Perioperative Care, Dell Medical School, The University of Texas at Austin, 1501 Red River Street, Austin, TX, 78702, USA.|Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, Austin, TX, 78712, USA.
Nicholas A
NA
Peppas
D000179:Acrylates / Q000138:chemical synthesis* / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D016923:Cell Death; D013006:Growth Hormone / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism; D009391:Nephelometry and Turbidimetry; D009994:Osmolar Concentration; D010047:Ovalbumin / Q000378:metabolism; D011109:Polymethacrylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D011205:Povidone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D011506:Proteins / Q000008:administration & dosage*; D017550:Spectroscopy, Fourier Transform Infrared; D034421:Sus scrofa; D013818:Thermogravimetry; D017186:Titrimetry
D000179:Acrylates; D007328:Insulin; D011109:Polymethacrylic Acids; D011506:Proteins; C000624148:poly(methacrylic acid-co-N-vinylpyrrolidone-g-polyethylene glycol); D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D013006:Growth Hormone; D010047:Ovalbumin; D011205:Povidone; C036658:acrylic acid
drug delivery systems; hydrogels; proteins; stimuli-sensitive polymers; swelling