Assessment of poly(methacrylic acid-co-N-vinyl pyrrolidone) as a carrier for the oral delivery of therapeutic proteins using Caco-2 and HT29-MTX cell lines.
Hydrogels of poly(methacrylic acid-co-N-vinyl pyrrolidone) were synthesized and evaluated for their use as carriers for oral protein delivery. Insulin loading efficiencies were determined to be near 90% for carriers crosslinked with ethylene glycol dimethacrylate with corresponding weight incorporation levels near 12%. Although no insulin was released in gastric conditions, as desired, near instantaneous release occurred when the pH was raised to values typical of the intestinal area. Cytocompatibility studies with Caco-2 and Caco-2/HT29-MTX cultures demonstrated that microparticles did not elicit toxic effects at concentrations up to 5.0 mg/mL. Insulin transport studies revealed that the carriers did not disrupt the cell layer and thus did not change the insulin permeability in the apical-to-basolateral direction. Therefore, microparticles of this system were best suited for oral delivery of therapeutic agents that do not require transport facilitation.
Carr
Daniel A
DA
Department of Chemical Engineering, The University of Texas at Austin, 1 University Station C0400, Austin, Texas 78712, USA.
Peppas
Nicholas A
NA
D000284:Administration, Oral; D000465:Algorithms; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005753:Gastric Mucosa / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D020100:Hydrogels; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D008422:Materials Testing; D008768:Methylmethacrylates / Q000737:chemistry*; D053758:Nanoparticles; D011205:Povidone / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage*
D004337:Drug Carriers; D020100:Hydrogels; D007004:Hypoglycemic Agents; D007328:Insulin; D008768:Methylmethacrylates; D011506:Proteins; C037334:poly(methylmethacrylate-N-vinylpyrrolidone); D011205:Povidone