Annals of Biomedical Engineering

, Volume 44, Issue 6, pp 1970–1982 | Cite as

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

  • Sarena D. Horava
  • Nicholas A. PeppasEmail author
Emerging Trends in Biomaterials Research


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.


Biomaterials Drug delivery Hydrogels Factor IX 



Fasted-state simulated gastric fluid


Fasted-state simulated intestinal fluid


Human factor IX


Methacrylic acid


Poly(ethylene glycol) dimethacrylate


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



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.

Supplementary material

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Supplementary material 1 (TIFF 163 kb)
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Supplementary material 2 (TIFF 4729 kb)
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Supplementary material 3 (TIFF 91 kb)


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Copyright information

© Biomedical Engineering Society 2016

Authors and Affiliations

  1. 1.McKetta Department of Chemical EngineeringThe University of Texas at AustinAustinUSA
  2. 2.Institute for Biomaterials, Drug Delivery, and Regenerative MedicineThe University of Texas at AustinAustinUSA
  3. 3.Department of Biomedical EngineeringThe University of Texas at AustinAustinUSA
  4. 4.Department of Surgery and Perioperative Care, Dell Medical SchoolThe University of Texas at AustinAustinUSA
  5. 5.Division of Pharmaceutics, College of PharmacyThe University of Texas at AustinAustinUSA

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