دانلود رایگان مقاله لاتین هیالورونیداز کایمریک از سایت الزویر
عنوان فارسی مقاله:
طراحی و آماده سازی هیالورونیداز کایمریک به عنوان مراقبی برای تجویز زیر جلدی بیوفارماکیوتیکال
عنوان انگلیسی مقاله:
Design and preparation of chimeric hyaluronidase as a chaperone for the subcutaneous administration of biopharmaceuticals
سال انتشار : 2016
برای دانلود رایگان مقاله هیالورونیداز کایمریک اینجا کلیک نمایید.
مقدمه انگلیسی مقاله:
1. Introduction
Subcutaneous (SC) administration for the delivery of biomacromolecular pharmaceuticals provides better safety and convenience than intravenous (IV) administration [1]. However, the bioavailabilities of SC-administered molecules would be lower than the IV route in general, especially for macromolecules [2], when in SC administration, the drugs have to pass through the complex three-dimensional extracellular matrix (ECM) of the dermis and then traverse capillaries or lymphatics in order to reach the general cardiovascular pool [3].Because the hyaluronan network constitutes the main filler in ECM and serves as a barrier for drug delivery, its breakup could loosen SC space and therefore enhance molecular dispersion [4]. In the past, hyaluronidases extracted from animal tissues were used as chaperone factors [5]. However, undefined impurities and heterogeneous ingredients may cause inflammation. Thus, these hyaluronidases were gradually substituted by recombinant human hyaluronidase rhPH20, which was approved by the FDA in 2005 [6]. As reported, rhPH20 efficiently elevated absolute bioavailabilities of the small molecules ondansetron, morphine and ceftriaxone to 79% [7], 103% [8] and 107% [9], respectively. For biomacromolecular pharmaceuticals, however, the results were not as significant as for the small molecules. Absolute bioavailabilities ranging from 40% to 94% were reported with rhPH20, and required the incorporation of other substances, such as heparin [10–12]. It is possible that the effect of hyaluronidase on the subcutaneous delivery of biomacromolecules is not long enough. Frost [4] reported that the ECM changes induced by rhPH20 were almost reversible within 24 h. This period may be short for macromolecules, whose convection and diffusion are much slower than smallmolecules. Furthermore, biomacromolecules such as proteinsare likely to be metabolized in the SC space. Retention in the SC space will lead to longer exposure to catabolic enzymes, while the promotion of intravascular uptake would reduce degradation. The extracellular matrix in the dermis has a complex composition and is made up of an intricate stereochemical structure, which the drugs have to pass through. Therefore, enough open time and space for the ECM “channel” may be helpful to minimize local entrapment and degradation, facilitating the macromolecule diffusion to the vascular compartment successfully. The question is why rhPH20 has so short an action time. Like other proteins, the hyaluronidase can be damaged in the subcutaneous environment through hydrolysis, enzymatic degradation, antigen-antibody reactions, or macrophage ingestion. Although the mechanism is not clear, it would be worthwhile to construct a new hyaluronidase with better durability than the current product against damaging factors, prolonging its role as a channel opener. The strategy in this paper was to conjugate hyaluronidase with human serum albumin (HSA) or the IgG Fc portion. HSA is the most abundant protein in blood plasma and is widely used as a stabilizing agent for therapeutic proteins in drug formulations. It consists of three conserved homologous structural motifs, each carrying a binding site specific for affinity chromatography [13]. Fusion of heterologous peptides with the IgG Fc portion provides stability for natural proteins [14]. Both HSA and Fc fragments have been used for the conjugation of pharmaceutical drugs and are safe in vivo [15]. Bearing this in mind, we explored whether these reconstruction techniques could improve stability in the dermis and thus exert long-lasting effects. Two pharmaceutical proteins, Stelara (150 kDa) and TFI (250 kDa), were chosen as model molecules to co-administered for pharmacokinetics study. Stelara, also named as ustekinumab, is used to treat patients with relapsing-remitting multiple sclerosis [16]. TFI (TNFR2-Fc-IL-1ra) is a bifunctional ligand with enhanced anti-inflammatory effect [17].
برای دانلود رایگان مقاله هیالورونیداز کایمریک اینجا کلیک نمایید.
کلمات کلیدی:
Enzymatic Copolymerization to Hybrid Glycosaminoglycans: A Novel ... pubs.acs.org/doi/pdf/10.1021/bm0700340 by H Ochiai - 2007 - Cited by 14 - Related articles molecularly designed carbohydrate monomers through non- biosynthetic ... Chimeric GAGs have been prepared by ... low yields. Very recently, another method to prepare chimeric .... hyalurolyticus hyaluronidase digestion at 0 and 24 h. Generating Porcine Chimeras Using Inner Cell Mass Cells and ... - PLOS journals.plos.org/plosone/article?id=10.1371/journal.pone.0061900 by K Nakano - 2013 - Cited by 12 - Related articles Apr 23, 2013 - The rate of production of chimeric blastocysts after aggregation with ... The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ... IVM oocytes with expanded cummulus cells were treated with 1 mg/ml hyaluronidase dissolved in Tyrode's ... A recombinant chimeric protein specifically induces mutant KRAS ... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190097/ by T Pan - 2016 - Related articles Jun 14, 2016 - Our findings indicate that recombinant PTD-RBD-VIF, a chimeric protein with a .... were digested with collagenase and hyaluronidase and cells were .... to the idea generation, experimental design, manuscript preparation and ... Design and syntheses of hyaluronan oligosaccharide conjugates as ... https://www.ncbi.nlm.nih.gov › NCBI › Literature › PubMed Central (PMC) by X Lu - 2015 - Cited by 1 - Related articles May 22, 2015 - The HA tetrasaccharide obtained was utilized to prepare multiple S-linked HA ... Keywords: CD44, Hyaluronan, Inhibitor design, Synthesis ... a CD44 HABD/IgGFc chimera onto anti-IgG antibody coated 96-well plates [24]. ... Due to the low cost of hyaluronidase (~ $100/g) and HA polysaccharide ($2/g), this ... Subcutaneous immunoglobulin: opportunities ... - Wiley Online Library onlinelibrary.wiley.com/doi/10.1111/j.1365-2249.2009.04027.x/abstract by S Misbah - 2009 - Cited by 87 - Related articles Oct 30, 2009 - For example, hyaluronidase-facilitated administration increases the bioavailability of SCIg, and may allow for the administration of larger ... Subcutaneous immunoglobulin: opportunities ... - Wiley Online Library onlinelibrary.wiley.com/doi/10.1111/j.1365-2249.2009.04027.x/full by S Misbah - 2009 - Cited by 86 - Related articles Oct 30, 2009 - For example, hyaluronidase-facilitated administration increases the bioavailability of .... the presentations focused upon the design of protocols for the use of SCIg in ..... of the AUC with the same 10% IgG preparation using the i.v. route. ..... Zhiguo Su, Design and preparation of chimeric hyaluronidase as a ...
