ENHANZE® drug delivery technology: a novel approach to subcutaneous administration using recombinant human hyaluronidase PH20

ENHANZE® drug delivery technology is based on the proprietary recombinant human hyaluronidase PH20 enzyme (rHuPH20; Halozyme Therapeutics, Inc.) that facilitates the subcutaneous (SC) delivery of co-administered therapeutics. rHuPH20 works by degrading the glycosaminoglycan hyaluronan (HA), which plays a role in resistance to bulk fluid flow in the SC space, limiting large volume SC drug delivery, dispersion, and absorption. Co-administration of rHuPH20 with partner therapies can overcome administration time and volume barriers associated with existing SC therapeutic formulations, and has been shown to reduce the burden on patients and healthcare providers compared with intravenous formulations. rHuPH20 (as HYLENEX® recombinant) is currently FDA-approved for subcutaneous fluid administration for achieving hydration, to increase the dispersion and absorption of other injected drugs, and in subcutaneous urography for improving resorption of radiopaque agents. rHuPH20 is also co-formulated with two anticancer therapies, trastuzumab (i.e. Herceptin® SC) and rituximab (i.e. RITUXAN HYCELA®/RITUXAN® SC/MabThera® SC) and dosed sequentially with human immunoglobin to treat primary immunodeficiency (i.e. HyQvia®/HYQVIA®). This article reviews pharmaceutical properties of rHuPH20, its current applications with approved therapeutics, and the potential for future developments.

Quantitation of the results of abdominal liposuction.

BACKGROUND: There are few objective techniques to accurately measure the outcome of liposuction. Consequently, there is also a paucity of data quantifying the results of this procedure. OBJECTIVES: The authors compare changes in abdominal volume and circumference with several objective measurement techniques in a relatively homogeneous group of individuals undergoing liposuction in a single, defined abdominal region. METHODS: This clinical study enrolled 23 patients with a body mass index (BMI) <25 kg/m(2) who had a localized anterior abdominal contour defect. Patients underwent standard suction-assisted tumescent liposuction. Changes in abdominal volume and circumference in the operative area (60 mm above to 80 mm below the umbilicus) preoperatively and 10 weeks postoperatively were assessed using a 3-dimensional (3D) digital photographic system and a standardized constant-tension manual tape measure procedure. RESULTS: The majority of the patients in this study were Caucasian women with a mean age of 42 years, a mean weight of 65.8 kg, and a mean BMI of 23.8 kg/m(2). In the study population, mean abdominal volume and umbilical circumference were reduced by 231.0 mL (~30% of subcutaneous fat) and 1.7 cm, respectively, at 10 weeks postoperatively as determined by 3D digital imaging. Fat volume in the surgical aspirate (mean = -183.3 mL) was a poor predictor of individual outcome, as assessed 10 weeks postoperatively by both the 3D digital imaging and multilevel constant-tension tape measure assessment tools. CONCLUSIONS: Both 3D digital photographic imaging and a standardized manual tape measurement procedure proved to be reliable tools for objectively assessing changes in abdominal circumference and volume produced by standard liposuction of a single, defined abdominal region.

MN-001, a novel oral anti-inflammatory agent, suppresses bladder hyperactivity in a rat model.

OBJECTIVE: To evaluate the effects of MN-001, a novel orally active anti-inflammatory agent, in suppressing the bladder hyperactivity resulting from ovalbumin (OA)-induced mast-cell stimulation in a rat model. MATERIALS AND METHODS: Sprague-Dawley rats of both sexes were divided into five groups of 10 each, with group 1 as the control and groups 2-5 undergoing OA sensitization to produce mast-cell degranulation using an established method. At 14 days after sensitization, rats were given an acute intravesical challenge: in group 1, by saline (control), and in groups 2-5, with approximately 2 mL of OA (10 mg/mL in sterile saline). Groups 3-5 received the investigational agent MN-001 orally at 10, 30 or 50 mg/kg, respectively, 1 h before intravesical OA challenge. Urodynamics were then evaluated to quantify the frequency of contractions (voids), intercontractile interval (ICI) and non-voiding contractions (NVCs). RESULTS: Acute intravesical OA challenge in rats in group 2 caused contractions of bladder smooth muscle, leading to a significant (P < 0.05) dose-dependent increase in NVCs and a decrease in ICI. Rats pre-treated with MN-001 at 30 and 50 mg/kg (groups 4 and 5) had significantly fewer NVCs and a greater ICI than rats in group 2 (P < 0.05). CONCLUSION: OA challenge in OA-sensitized rats produces bladder hyperactivity, as reflected in significantly more NVCs and a lower ICI. At doses of 30 and 50 mg/kg orally, MN-001 produces significant protection against the OA-induced bladder hyperactivity. MN-001 might have a role in managing mast cell activity and the associated bladder symptoms in patients with interstitial cystitis.

The effects of citicoline and lamotrigine alone and in combination following permanent middle cerebral artery occlusion in rats.

The neuroprotective efficacies of citicoline and lamotrigine, alone and in combination, were investigated in experimental permanent focal ischemia. Seven groups of adult male rats underwent focal cerebral ischemia and were given the following treatments: placebo (P), low and high doses of citicoline (C250 and C500, 250 and 500 mg/kg/day i.p., respectively), low and high doses of lamotrigine (L50 and L100, 50 and 100 mg/kg/day p.o., respectively), and combination regimes of both drugs in low (C250 + L50) and high doses (C500 + L100). Citicoline, but not lamotrigine, exerted neuroprotective efficacy during this acute ischemic stroke model. The citicoline and lamotrigine combination did not provide a significant additive neuroprotective effect.