A recombinant human enzyme for enhanced interstitial transport of therapeutics
| Autor: | J.E. Lim, M.L. Zepeda, H. M. Shepard, Bookbinder Louis H, Gregory I. Frost, John S. Patton, M.F. Haller, A. Hofer, Gilbert A. Keller, Thomas S. Edgington |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Drug Injections Subcutaneous media_common.quotation_subject medicine.medical_treatment Biological Availability Biological Transport Active Hyaluronoglucosaminidase Mice Nude Pharmaceutical Science Inflammation Pharmacology Adenoviridae Polyethylene Glycols Capillary Permeability Mice Drug Delivery Systems Drug Therapy Pharmacokinetics Interstitial matrix Hyaluronidase Animals Humans Medicine Particle Size media_common business.industry Antibodies Monoclonal Endothelial Cells Genetic Therapy Macaca mulatta Recombinant Proteins Capillaries Bioavailability Molecular Weight Cytokine Pharmaceutical Preparations Recombinant Human Hyaluronidase Antibody Formation Interferon Type I Cytokines Female medicine.symptom business medicine.drug |
| Zdroj: | Journal of Controlled Release. 114:230-241 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2006.05.027 |
| Popis: | Subcutaneously injected therapeutics must pass through the interstitial matrix of the skin in order to reach their intended targets. This complex, three-dimensional structure limits the type and quantity of drugs that can be administered by local injection. Here we found that depolymerization of the viscoelastic component of the interstitial matrix in animal models with a highly purified recombinant human hyaluronidase enzyme (rHuPH20) increased the dispersion of locally injected drugs, across a broad range of molecular weights without tissue distortion. rHuPH20 increased infusion rates and the pattern and extent of appearance of locally injected drugs in systemic blood. In particular, rHuPH20 changed the pharmacokinetic profiles and significantly augmented the absolute bioavailability of locally injected large protein therapeutics. Importantly, within 24 h of injection, the interstitial viscoelastic barriers were restored without histologic alterations or signs of inflammation. rHuPH20 may function as an interstitial delivery enhancing agent capable of increasing the dispersion and bioavailability of coinjected drugs that may enable subcutaneous administration of therapeutics and replace intravenous delivery. |
| Databáze: | OpenAIRE |
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