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Cited by 323Proteoglycans and glycosaminoglycans researchIntramuscular injections and effectsHydrogels: synthesis, properties, applications

Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration

Frost, Gregory I·2007·Expert Opinion on Drug Delivery
DOI 10.1517/17425247.4.4.427
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Abstract

The extracellular matrix is a significant barrier to the effective subcutaneous delivery of many drugs, limiting both pharmacokinetic parameters and injection volumes. The space outside adipocytes in the hypodermis is not a fluid, but rather a solid extracellular matrix of collageneous fibrils embedded within a glycosaminoglycan-rich viscoelastic gel that buffers convective forces. The extracellular matrix limits the volume of drug that can be injected at a single site, as well as the rate and amount that reach the vascular compartment. A fully human recombinant DNA-derived hyaluronidase enzyme (rHuPH20) has been developed to leverage the historical efficacy of animal testes extract-derived spreading factors to reversibly modify the hypodermis, in light of discovery of the human hyaluronidase gene family. The application of this technology to increase both injection volumes and bioavailability from subcutaneous injection may overcome some key limitations of this route of administration in multiple settings of care.

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Crossref · 10.1517/17425247.4.4.427

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66 of 66 references verified0 citation errors · 0 not checkable

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  • Coadministration of the dispersion enhancer hyaluronidase facilitates spreading of an injected volume in the subcutaneous interstitial space and enables injection of a larger volume at an individualized rate at the patient's preferred injection site.

    “it has been shown that coadministration of the dispersion enhancer hyaluronidase facilitates spreading of an injected volume in the subcutaneous interstitial space and, therefore, enables injection of a larger volume at an individualized rate at the patient’s preferred injection site (e.g. thigh, abdomen, or upper arm) [18].”

    From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [18]

  • Hyaluronan provides a barrier against the spreading of injected fluids.

    “Hyaluronan provides a barrier against the spreading of injected fluids [18].”

    From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [18]

  • Intravenous doses of rHuPH20 from 38 to 12,000 units/kg in rhesus primates and 10,500 units/kg in rodents have been generally well-tolerated.

    “Intravenous doses from 38 to 12,000 units/kg in rhesus primates and 10,500 units/kg in rodents have been generally well-tolerated.”

    From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [18]

  • In primates, rHuPH20 has been shown to be well-tolerated at 45,000 units per subcutaneous injection and 4500 units per periocular injection.

    “In primates, rHuPH20 has been shown to be well-tolerated at 45,000 units per subcutaneous injection and 4500 units per periocular injection.”

    From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [18]

  • Subcutaneous infusions can be coadministered or produced as coformulations with the dispersion-enhancer hyaluronidase, an enzyme that facilitates spreading of an injected fluid in the subcutaneous tissue.

    “In an attempt to increase the subcutaneous bioavailability of a biotherapeutic, subcutaneous infusions can be coadministered (or produced as coformulations) with the dispersion-enhancer hyaluronidase (discussed in detail in Sect. 4), an enzyme that facilitates spreading of an injected fluid in the subcutaneous tissue [18].”

    From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [18]

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Authors
Frost, G. I.
Affiliations
Halozyme Therapeutics (United States) (US)
Corresponding author
Frost, Gregory I
Venue
Expert Opinion on Drug Delivery
Publisher
Informa UK Limited
Published
2007-07
Volume
4
Issue
4
Pages
427-440
ISSN
  • 1742-5247 (ISSN-L)
  • 1744-7593
DOI
10.1517/17425247.4.4.427
OpenAlex
W2158548553
Cited by
323
References
66
Citations by year
2026: 25 · 2025: 18 · 2024: 16 · 2023: 23 · 2022: 15 · 2021: 27 · 2020: 18 · 2019: 8 · 2018: 27 · 2017: 18 · 2016: 19 · 2015: 17 · 2014: 28 · 2013: 12 · 2012: 23
FWCI
0.45
Type
journal article
Language
en
Open access
closed
Locations
  • Expert Opinion on Drug Delivery (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Health Sciences › Medicine › Emergency Medicine › Intramuscular injections and effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
Keywords
recombinant human hyaluronidase, rHuPH20, subcutaneous drug delivery, extracellular matrix, hyaluronic acid, subcutaneous tissue, injection volume, bioavailability, hyaluronidase, glycosaminoglycans, collagen, pharmacokinetics
MeSH terms
Amino Acid Sequence, Animals, Extracellular Matrix, Humans, Hyaluronoglucosaminidase, Injections, Subcutaneous, Molecular Sequence Data, Recombinant Proteins, Solubility, Protein Engineering, Cell Adhesion Molecules, Dermis

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