Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Electrogene transfer (EGT) of plasmid DNA into skeletal muscle is a promising strategy for the treatment of muscle disorders and for the systemic secretion of therapeutic proteins. We report here that preinjecting hyaluronidase (HYAse) significantly increases the gene transfer efficiency of muscle EGT. Three constructs encoding mouse erythropoietin (pCMV/mEPO), secreted alkaline phosphatase (pCMV/SeAP), and luciferase (pGGluc) were electroinjected intramuscularly in BALB/c mice and rabbits with and without HYAse pretreatment. Preinjection 1 or 4 hr before EGT increased EPO gene expression by about 5-fold in mice and maintained higher gene expression than plasmid EGT alone. A similar increment in gene expression was observed on pretreatment with HYAse and electroinjection of pCMV/mEPO into rabbit tibialis muscle. The increment of gene expression in rabbits reached 17-fold on injection of plasmid pCMV/SeAP and 24-fold with plasmid pGGluc. Injection of a plasmid encoding beta-galactosidase (pCMV/beta gal/NLS) and subsequent staining with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside indicated that HYAse increased the tissue area involved in gene expression. No irreversible tissue damage was observed on histological analysis of treated muscles. HYAse is used in a variety of clinical applications, and thus the combination of HYAse pretreatment and muscle EGT may constitute an efficient gene transfer method to achieve therapeutic levels of gene expression.
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PMID:Hyaluronidase increases electrogene transfer efficiency in skeletal muscle. 1186 Jul 3

An injectable hyaluronic acid (HA) microhydrogel was successfully developed as a novel drug carrier for controlled release formulation of protein drugs. HA hydrogels were prepared by the disulfide bond formation of thiolated HA (HA-SH). EPO was loaded in situ during HA-SH hydrogel preparation using an accelerating agent of sodium tetrathionate. The gelation time was drastically reduced from a day to 30 min when sodium tetrathionate was added for HA-SH hydrogel preparation. In vitro release of EPO in PBS at 37 degrees C showed that EPO was rapidly released for 3 days with an initial burst and then slowly up to 9 days from HA-SH hydrogels. HA-SH microhydrogels were prepared by the reactive spray drying of diluted HA-SH precursor solution. The mean particle size was approximately 2.3 mum and the water content after spray drying was approximately 14%. Ellman's test showed that sodium tetrathionate contributed not only for rapid crosslinking reaction but also for the reduction of residual free thiol content in HA-SH microhydrogels after spray drying. EPO recovery from HA-SH microhydrogels after degradation with hyaluronidase SD was higher than 95%. The released EPO appeared to be intact from the analysis with RP-HPLC. According to in vivo release test of EPO from HA-SH microhydrogels in Sprague Dawley (SD) rats, elevated plasma concentration of EPO higher than 0.1 ng/mL, which is a critical minimal concentration for EPO efficacy, was maintained up to 7 days. There was no adverse effect during and after the in vivo tests.
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PMID:Injectable hyaluronic acid microhydrogels for controlled release formulation of erythropoietin. 1707 46