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Design of pH-Responsive Biomaterials to Enable the Oral Route of Hematological Factor IX

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Abstract

The oral administration of hematological factor IX (FIX) can offer a convenient prophylactic treatment for hemophilia B patients. pH-Responsive hydrogels based on poly(methacrylic acid)-grafted-poly(ethylene glycol) (P(MAA-g-EG)) have been engineered as delivery vehicles for FIX. In oral delivery, such hydrogel carriers protected FIX from the gastric environment and released it under intestinal conditions as demonstrated by evaluation of the loading and release of FIX. Tailoring of the hydrogel networks improved the loading of FIX within the microcarriers, which is critical for minimizing protein degradation. Optimizing the loading conditions by increasing the incubation time and using a reduced ionic strength buffer further improved the delivery potential of the microcarriers. The presence of the microcarriers significantly enhanced the oral absorption of FIX in vitro. As shown in this work, P(MAA-g-EG) microcarriers are promising candidates for the oral delivery of FIX.

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Abbreviations

FaSSGF:

Fasted-state simulated gastric fluid

FaSSIF:

Fasted-state simulated intestinal fluid

hFIX:

Human factor IX

MAA:

Methacrylic acid

PEGDMA:

Poly(ethylene glycol) dimethacrylate

P(MAA-g-EG):

Poly(methacrylic acid)-grafted-poly(ethylene glycol)

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Acknowledgments

This work was supported in part by a grant from the National Institutes of Health (R01-EB-000246-21) and the Fletcher S. Pratt Foundation. SDH acknowledges support from the National Science Foundation Graduate Research Fellowship Program (DGE-1110007) and the P.E.O. Scholar Award. The authors thank the Microscopy and Imaging Facility of the Institute for Cellular and Molecular Biology at The University of Texas at Austin for facilitating the use of SEM microscopy. The authors would also like to acknowledge Katie Moy and Joel Liou for their assistance with polymer synthesis and characterization.

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Authors and Affiliations

  1. McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA

    Sarena D. Horava & Nicholas A. Peppas

  2. Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, Austin, TX, USA

    Sarena D. Horava & Nicholas A. Peppas

  3. Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA

    Nicholas A. Peppas

  4. Department of Surgery and Perioperative Care, Dell Medical School, The University of Texas at Austin, Austin, TX, USA

    Nicholas A. Peppas

  5. Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA

    Nicholas A. Peppas

Authors
  1. Sarena D. Horava
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  2. Nicholas A. Peppas
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Correspondence to Nicholas A. Peppas.

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Associate Editor Michael S. Detamore oversaw the review of this article.

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Horava, S.D., Peppas, N.A. Design of pH-Responsive Biomaterials to Enable the Oral Route of Hematological Factor IX. Ann Biomed Eng 44, 1970–1982 (2016). https://doi.org/10.1007/s10439-016-1566-x

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  • DOI: https://doi.org/10.1007/s10439-016-1566-x

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