pH-Responsive poly(itaconic acid-co-N-vinylpyrrolidone) hydrogels with reduced ionic strength loading solutions offer improved oral delivery potential for high isoelectric point-exhibiting therapeutic proteins.
pH-Responsive hydrogels comprised of itaconic acid copolymerized with N-vinylpyrrolidone (P(IA-co-NVP)) were synthesized and tested as carriers for the oral delivery of high isoelectric point (pI) exhibiting therapeutic proteins. Swelling studies show that P(IA-co-NVP) hydrogels exhibit significantly greater and faster pH-responsive swelling than previously studied methacrylic acid-based hydrogels, achieving up to 68% greater equilibrium swelling and 10.4 times greater swelling in time-limited experiments. Using salmon calcitonin as a model high pI protein therapeutic, we show that P(IA-co-NVP) hydrogels exhibit significantly greater delivery potential than methacrylic acid-based hydrogels. Additionally, we show that utilizing a lower ionic strength solution during drug loading significantly improves drug delivery potential for high pI therapeutics. By using a 1.5mM PBS buffer rather than the standard 150 mM PBS buffer during loading, up to 83 times as much calcitonin can be delivered in neutral conditions, with up to a 9.6-fold improvement in percent release. Using P(IA-co-NVP) hydrogel microparticles and a low ionic strength loading solution, up to 48 μg calcitonin/mg hydrogel can be delivered in small intestinal conditions. Based on expected absorption in the small intestine, this is sufficient delivery potential for achieving therapeutic dosage via a single, regularly-sized pill taken daily.
McKetta Department of Chemical Engineering, The University of Texas at Austin, C0400, Austin, TX 78712, United States. Electronic address: mkoetting@utexas.edu.
Michael C
MC
Koetting
McKetta Department of Chemical Engineering, The University of Texas at Austin, C0400, Austin, TX 78712, United States; Department of Biomedical Engineering, The University of Texas at Austin, C0800, Austin, TX 78712, United States; College of Pharmacy, The University of Texas at Austin, C0400, Austin, TX 78712, United States. Electronic address: peppas@che.utexas.edu.
Nicholas A
NA
Peppas
D000284:Administration, Oral; D018938:Caco-2 Cells; D002116:Calcitonin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D065546:Drug Liberation; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D007526:Isoelectric Point; D009994:Osmolar Concentration; D011108:Polymers / Q000737:chemistry* / Q000633:toxicity; D011760:Pyrrolidinones / Q000737:chemistry* / Q000633:toxicity; D012996:Solutions
D004337:Drug Carriers; D020100:Hydrogels; D011108:Polymers; D011760:Pyrrolidinones; D012996:Solutions; C000595245:poly(itaconic acid-co-N-vinylpyrrolidone); C028815:salmon calcitonin; D002116:Calcitonin
Ionic strength; Isoelectric point; Itaconic acid; Oral drug delivery; Protein therapeutics; pH-Responsive hydrogels