Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration.
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.
Frost
Gregory I
GI
Halozyme Therapeutics, Inc., 11588 Sorrento Valley Road, San Diego, CA 92121, USA. gfrost@halozyme.com
D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020405:Dermis / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008969:Molecular Sequence Data; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D012995:Solubility
D015815:Cell Adhesion Molecules; D011994:Recombinant Proteins; D006821:Hyaluronoglucosaminidase; C066852:hyaluronidase PH-20