Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration
Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration
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DOI：
10.1517/17425247.4.4.427
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发表时间：
2007-07-01
影响因子：
6.6
通讯作者：
Frost, Gregory I.
中科院分区：
文献类型：
--
作者：
Frost, Gregory I.
细胞外基质是许多药物有效皮下递送的重要障碍，限制了药代动力学参数和注射体积。皮下组织中脂肪细胞外的空间不是流体，而是包埋在富含糖胺聚糖的粘弹性凝胶内的胶原纤维的固体细胞外基质，其缓冲对流力。细胞外基质限制了可以在单个部位注射的药物体积，以及到达血管室的速率和量。根据人透明质酸酶基因家族的发现，已经开发了完全人重组DNA衍生的透明质酸酶（rHuPH 20），以利用动物睾丸提取物衍生的扩散因子的历史功效来可逆地修饰皮下组织。应用该技术增加皮下注射的注射体积和生物利用度可以克服该给药途径在多种护理环境中的一些关键限制。
The extracellular matrix is a significant barrier to the effective subcutaneous delivery of many drugs, limiting both pharmacokinetic parameters and injection volumes. The space outside adipocytes in the hypodermis is not a fluid, but rather a solid extracellular matrix of collageneous fibrils embedded within a glycosaminoglycan-rich viscoelastic gel that buffers convective forces. The extracellular matrix limits the volume of drug that can be injected at a single site, as well as the rate and amount that reach the vascular compartment. A fully human recombinant DNA-derived hyaluronidase enzyme (rHuPH20) has been developed to leverage the historical efficacy of animal testes extract-derived spreading factors to reversibly modify the hypodermis, in light of discovery of the human hyaluronidase gene family.. The application of this technology to increase both injection volumes and bioavailability from subcutaneous injection may overcome some key limitations of this route of administration in multiple settings of care.