recombinant human hyaluronidase
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Author(s):  
Stephen P. Knowles ◽  
Marie A. Printz ◽  
David W. Kang ◽  
Michael J. LaBarre ◽  
Renee P. Tannenbaum

Author(s):  
Lavinia Morosi ◽  
Marina Meroni ◽  
Paolo Ubezio ◽  
Ilaria Fuso Nerini ◽  
Lucia Minoli ◽  
...  

Abstract Background Scarce drug penetration in solid tumours is one of the possible causes of the limited efficacy of chemotherapy and is related to the altered tumour microenvironment. The abnormal tumour extracellular matrix (ECM) together with abnormal blood and lymphatic vessels, reactive stroma and inflammation all affect the uptake, distribution and efficacy of anticancer drugs. Methods We investigated the effect of PEGylated recombinant human hyaluronidase PH20 (PEGPH20) pre-treatment in degrading hyaluronan (hyaluronic acid; HA), one of the main components of the ECM, to improve the delivery of antitumor drugs and increase their therapeutic efficacy. The antitumor activity of paclitaxel (PTX) in HA synthase 3-overexpressing and wild-type SKOV3 ovarian cancer model and in the BxPC3 pancreas xenograft tumour model, was evaluated by monitoring tumour growth with or without PEGPH20 pre-treatment. Pharmacokinetics and tumour penetration of PTX were assessed by HPLC and mass spectrometry imaging analysis in the same tumour models. Tumour tissue architecture and HA deposition were analysed by histochemistry. Results Pre-treatment with PEGPH20 modified tumour tissue architecture and improved the antitumor activity of paclitaxel in the SKOV3/HAS3 tumour model, favouring its accumulation and more homogeneous intra-tumour distribution, as assessed by quantitative and qualitative analysis. PEGPH20 also reduced HA content influencing, though less markedly, PTX distribution and antitumor activity in the BxPC3 tumour model. Conclusion Remodelling the stroma of HA-rich tumours by depletion of HA with PEGPH20 pre-treatment, is a potentially successful strategy to improve the intra-tumour distribution of anticancer drugs, increasing their therapeutic efficacy, without increasing toxicity.


Author(s):  
Sneha Pervin ◽  
Somsubhra Ghosh ◽  
Sankhadip Bose ◽  
Nandan Sarkar

Primary immunodeficiency disorder (PID) refers to a heterogeneous cluster of over 350 syndromes that upshot from defects in the immune system development or function. PIDs are broadly classified as disorders of adaptive immunity or innate immunity. The enhanced efficacy of human immune serum globulin 10% with recombinant human Hyaluronidase with comparison to blood vessel human gamma globulin is a very prospective open-label study for PID. Treatment of primary immunological disorder diseases (PIDD) with Subcutaneous(SC) infusions of immune gamma globulin headed by an injection of hyazyme to extend SC tissue porousness was evaluated in two consecutive, prospective, non-controlled, multi-center studies. HYQVIA could be a subcutaneously mediated medication to treat the primary immunological disorder in adults. ENHANZE® drug delivery technology relies on the proprietary rHuPH20 macromolecule that facilitates the SC delivery of co administered medical specialty. Recombinant Human Hyaluronidase works by degrading the glycosaminoglycan hyaluronan, which plays a role in resistance to excessive flow of fluid within the Subcutaneous matrix, limiting massive volume SC drug delivery, dispersion, and absorption. Co-administration of recombinant Hyazyme with partner therapies can overcome administration time and volume barriers associated with existing SC therapeutic formulations.


PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254765
Author(s):  
David W. Kang ◽  
Beate Bittner ◽  
Barry J. Sugarman ◽  
Monica L. Zepeda ◽  
Marie A. Printz

Background Recombinant human hyaluronidase PH20 (rHuPH20) facilitates the dispersion and absorption of subcutaneously administered therapeutic agents. This study aimed to characterize the transient, local action of rHuPH20 in the subcutaneous (SC) space using focused biodistribution and dye dispersion studies conducted in mice. Materials and methods To evaluate the biodistribution of rHuPH20, mice were intradermally administered rHuPH20 (80 U). The enzymatic activity of rHuPH20 was analyzed in the skin, lymph nodes, and plasma. Animal model sensitivity was determined by intravenous administration of rHuPH20 (80 U) to the tail vein. To evaluate local dispersion, mice received an intradermal injection of rHuPH20 followed by an intradermal injection of Trypan Blue dye at a contralateral site 45 minutes later. Dye dispersion was measured using a digital caliper. Results After intradermal rHuPH20 injection, enzymatic activity was detected within the skin near the injection site with levels decreasing rapidly after 15 minutes. There was no clear evidence of systemic exposure after administration of rHuPH20, and no discernible rHuPH20 activity was observed in lymph or plasma as a function of time after dosing. In the dye dispersion study, delivery of rHuPH20 at one site did not impact dye dispersion at a distal skin site. Conclusion These observations support the classification of rHuPH20 as a transiently active and locally acting permeation enhancer.


Author(s):  
Ji Hye Lee ◽  
Miyoun Yoo ◽  
Sang Mee Lee ◽  
Soon-Jae Park ◽  
Tae Young Kil ◽  
...  

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Galen H. Shi ◽  
Robert J. Connor ◽  
David S. Collins ◽  
David W. Kang

AbstractRecombinant human hyaluronidase PH20 (rHuPH20) facilitates subcutaneous (SC) delivery of co-administered therapeutic agents by locally and transiently degrading hyaluronan in the SC space, and can be administered with therapeutics using a variety of devices. Two SC delivery studies were carried out to assess auto-injector (AI) performance, each in 18 Yucatan miniature pigs. Abdominal injections were administered using three auto-injectors of 1 mL (AI1) and 2 mL (AI2 and sAI2) with different injection speeds and depths (5.5–7.5 mm) and two pre-filled syringe (PFS) devices of 1 and 2 mL. The injection included a placebo buffer with and without rHuPH20 to evaluate the effect of rHuPH20 on SC injection performance. The feasibility of using similar devices to deliver a placebo buffer in humans was investigated. rHuPH20 was not studied in humans. In miniature pigs, postinjection swelling was evident for most PFS/AI injections, particularly 2 mL. Swelling heights and back leakage were typically lower with rHuPH20 co-administration versus placebo for most device configurations (1 or 2 mL PFS or AI). Auto-injections with versus without rHuPH20 also resulted in reduced swelling firmness and faster swelling resolution over time. Slow injections with rHuPH20 had shorter and more consistent injection time versus placebo. In humans, minimal injection site swelling and negligible back leakage were observed for 2-mL injections of placebo, while more erythema was observed in humans versus miniature pigs. Even at high delivery rates with PFS or AI, the addition of rHuPH20 resulted in improved SC injection performance versus placebo in miniature pigs.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Jessica A. Cowell ◽  
Marie A. Printz ◽  
Curtis B. Thompson

Abstract Objectives Drug–drug interaction studies for hyaluronidase safety assessments have evaluated only animal-derived enzyme preparations. We therefore set out to evaluate whether high-dose administration of two antihistamines, a potent corticosteroid, steroid hormone, adrenocorticotropic hormone (ACTH), or salicylic acid would alter the dispersive activity of recombinant human hyaluronidase PH20 (rHuPH20). Methods NCr nu/nu mice were pretreated with diphenhydramine, cetirizine, dexamethasone, estrogen, ACTH, salicylic acid, and/or neutral-buffered saline (NBS). An hour following final pretreatment, dosed mice were anesthetized with ketamine/xylazine and placed in an imaging chamber. A 120 mg/mL immunoglobulin G (IgG) solution with 0.3 μg/mL IgGDL755 (labeled IgG) was injected intradermally, with/without 2,000 U/mL rHuPH20. Fluorescent images of labeled IgG dispersion were acquired ≤20 min post injection. Results Dispersion of high-concentration labeled IgG combined with rHuPH20 was greater at all time points vs. antibody alone. At 20 min post injection (last time point), the antibody dispersion area was significantly increased with rHuPH20 vs. without rHuPH20 (p≤0.005). The relative percent increase in antibody dispersion with rHuPH20 ranged from 22.8‒106.6% over the 20-min time course, compared with the corresponding non-rHuPH20 treated groups. The area of labeled IgG dispersion was statistically similar between rHuPH20 groups pretreated with an active compound and their paired NBS pretreated controls. Conclusions The addition of 2,000 U/mL rHuPH20 to a high-concentration antibody solution reproducibly incre-ased local antibody dispersion. Systemic pretreatment with diphenhydramine, cetirizine, dexamethasone, estrogen, ACTH, or salicylic acid did not affect the enzymatic spreading activity of rHuPH20, as measured by intradermal dispersion of labeled IgG in mice.


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