Hyaluronan in cytosol--microinjection-based probing of its existence and suggested functions.

Hyaluronan (HA) is a large glycosaminoglycan produced by hyaluronan synthases (HAS), enzymes normally active at plasma membrane. While HA is delivered into the extracellular space, intracellular HA is also seen, mostly in vesicular structures, but there are also reports on its presence in the cytosol and specific locations and functions there. We probed the possibility of HA localization and functions in cytosol by microinjecting fluorescent HA binding complex (fHABC), HA fragments and hyaluronidase (HYAL) into cytosol.

Subcutaneous drug delivery: a route to increased safety, patient satisfaction, and reduced costs.

The subcutaneous (SC) route of administration is generally preferred over intravenous administration because it enables at-home injection, improves quality of life, and reduces health care costs. In general, a volume of no greater than 1 to 2 mL is injected SC; however, for high-dose agents with limited solubility, such as monoclonal antibodies, larger volumes must be administered, which requires divided doses, smaller volumes, or more frequent dose administration. Therapeutics are being formulated with an enzyme, recombinant human hyaluronidase, to enhance the dispersion and absorption of SC administered therapeutics by transiently depolymerizing hyaluronan, a major component of the interstitial matrix.

The INFUSE-Morphine IIB study: use of recombinant human hyaluronidase (rHuPH20) to enhance the absorption of subcutaneous morphine in healthy volunteers.

Morphine is usually given intravenously (IV) for the treatment of moderate-to-severe pain, but subcutaneous (SC) administration is a viable alternative for parenteral delivery. The pharmacokinetics of SC morphine may be enhanced by coadministration with a hyaluronidase product. In this Phase IV, double-blind, randomized, crossover study, 18 healthy adults received a single dose of 2mg morphine SC with 150U of recombinant human hyaluronidase (rHuPH20), SC with 0.

The INFUSE-Morphine study: use of recombinant human hyaluronidase (rHuPH20) to enhance the absorption of subcutaneously administered morphine in patients with advanced illness.

Morphine is often administered by the subcutaneous (SC) route when venous access is difficult to achieve. Hyaluronidase temporarily increases the permeability of SC connective tissues by degrading hyaluronan and has been shown to increase the dispersion and absorption of coadministered molecules. Therefore, hyaluronidase could enhance the pharmacokinetics of subcutaneous morphine.

Assessing the role of human recombinant hyaluronidase in gravity-driven subcutaneous hydration: the INFUSE-LR study.

Background: Subcutaneous hydration has potential advantages over intravenous. Despite studies supporting the efficacy and safety of subcutaneous hydration it has not been studied extensively to date either with or without hyaluronidase.

Objectives: To compare flow rate, tolerability, and safety of gravity-driven subcutaneous fluid administration with and without recombinant human hyaluronidase (rHuPH20) in healthy volunteers.

In vitro release of vascular endothelial growth factor from gadolinium-doped biodegradable microspheres.

A drug delivery vehicle was constructed that could be visualized noninvasively with MRI. The biodegradable polymer poly(DL-lactic-co-glycolic acid) (PLGA) was used to fabricate microspheres containing vascular endothelial growth factor (VEGF) and the MRI contrast agent gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). The microspheres were characterized in terms of size, drug and contrast agent encapsulation, and degradation rate.