472815 Design,Development and Optimization of pH-Responsive Hydrogels for the Oral Delivery of Human Growth Hormone

Thursday, November 17, 2016: 9:10 AM
Continental 5 (Hilton San Francisco Union Square)
Stephanie Steichen1,2, Nicholas Peppas1,2,3,4 and Colleen O'Connor1, (1)Biomedical Engineering, The University of Texas at Austin, Austin, TX, (2)Institute for Biomaterials, Drug Delivery and Regenerative Medicine, Austin, TX, (3)Chemical Engineering, The University of Texas at Austin, Austin, TX, (4)Pharmacy, The University of Texas at Austin, Austin, TX

Protein therapeutics have the potential to treat a variety of debilitating disorders ranging from diabetes, growth hormone deficiencies, and even certain forms of cancer. However, due to their large and low stability, their administration has been traditionally limited painful and embarassing injections. An orally delivered carrier capable of protecting the delicate cargo during its transit through the gastrointestinal tract and undergoing targeting delivery to the absorptive region of the upper small intestine has the potential to overcome limits of protein stability, improve oral bioavailability and provide a more patient tolerated means of protein administration. To this end, a pH-responsive hydrogel carrier composed of methacrylic acid (MAA), N-vinyl pyrrolidone (NVP), and poly(ethylene glycol), P((MAA-co-NVP)-g-EG), was developed to deliver higher molecular weight protein therapeutics via the oral route. By varying crosslinking density and length, the swelling behavior of these gels could be modulated and adjusted to accomodate the larger protein, with loading efficiencies up to 60% for human growth hormone. Additionally, due to their pH-responsive behavior, the protein was not released under simulated gastric conditions but was preferentially released in simulated intestinal conditions. The hydrogel carriers also proved to be non-toxic in both model intestinal cell lines - Caco-2 and HT29-MTX - and in vivo upon administration to C57Bl/6 mice. Finally, when administered to the intestine, human growth hormone loaded P((MAA-co-NVP)-g-EG) hydrogels successfully delivered their protein payload with oral bioavailabilities of 0.5 - 5%, which is similar to other reported oral delivery stratgies for protein therapeutics.

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