Drug Delivery and Translational Research

, Volume 2, Issue 4, pp 254–264 | Cite as

Recombinant human hyaluronidase PH20 (rHuPH20) facilitates subcutaneous infusions of large volumes of immunoglobulin in a swine model

  • David W. KangEmail author
  • Laurence Jadin
  • Tara Nekoroski
  • Fred H. Drake
  • Monica L. Zepeda
Research Article


Many patients with primary immunodeficiency disease (PIDD) require lifelong immunoglobulin (Ig) replacement therapy. Home-based subcutaneous (SC) infusion provides advantages to patients with PIDD compared to hospital-based intravenous infusion. One limitation of current practice with SCIg infusion is the need for small-volume infusions at multiple injection sites on a frequent basis. A method was developed for large-volume SC infusion that uses preinfusion of recombinant human hyaluronidase (rHuPH20) to facilitate fluid dispersion. Miniature swine was used as a preclinical model to assess the effects of rHuPH20-facilitated infusions, of a single monthly dose, on fluid dispersion, infusion-related pressure, swelling, induration, and tissue damage. Preinfusion of vehicle (control) or rHuPH20 (75 U/g Ig) was performed simultaneously on contralateral abdominal sites on each animal, followed by infusion of 300 mL 10 % Ig (30 g) at each site. Compared to control infusions, rHuPH20 significantly reduced infusion pressure and induration (p < 0.05) and accelerated postinfusion Ig dispersion. Histological evaluation of infusion site tissue showed moderate to severe swelling for the control. Swelling after rHuPH20-facilitated infusion was mild on day 1 and had completely resolved shortly thereafter. Laser Doppler imaging of control infusion sites revealed local cutaneous hypoperfusion during Ig infusion, which was reduced almost 7-fold (p < 0.05) with the use of rHuPH20. These results demonstrate that rHuPH20-facilitated Ig infusion is associated with improved dispersion of Ig, resulting in reduced tissue pressure, induration, and reduced risk of tissue damage from mechanical trauma or local ischemia, thus enabling SC administration of large volumes of Ig at a single site.


Recombinant human hyaluronidase Subcutaneous infusion Immunoglobulin Primary immunodeficiency disease Induration Miniature swine 



The authors would like to thank Ghia Bacani for formulation support, James Skipper and Adrian Radi for assistance with the preclinical studies, Rebecca Symons for histology support, Dr. Michael J. Tomlinson for histopathological assessment, Dr. Ping Jiang for statistical analysis of the histopathological assessment, and Drs. Daniel C. Maneval, David A. Gold, Curtis B. Thompson, and H. Michael Shepard for critical review of the manuscript. Medical writing support, funded by Baxter BioScience, was provided by Roland Tacke, Candace Lundin, and Josh Collis of Gardiner-Caldwell Communications.


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Copyright information

© Controlled Release Society 2012

Authors and Affiliations

  • David W. Kang
    • 1
    Email author
  • Laurence Jadin
    • 1
  • Tara Nekoroski
    • 1
  • Fred H. Drake
    • 1
  • Monica L. Zepeda
    • 1
  1. 1.Halozyme Therapeutics, IncSan DiegoUSA

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