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The Accelerated Blood Clearance Phenomenon of PEGylated Nanocarriers
Published in Raj Bawa, János Szebeni, Thomas J. Webster, Gerald F. Audette, Immune Aspects of Biopharmaceuticals and Nanomedicines, 2019
Amr S. Abu Lila, Tatsuhiro Ishida
PEGylation refers to the conjugation of polyethylene glycol (PEG), and it has been extensively applied in the pharmaceutical industry, particularly in the field of drug delivery, in order to improve the pharmacokinetic behavior of PEGylated therapeutics [1]. The crucial role of PEGylation derives mainly from the ability of PEG, a hydrophilic polymer, to attract water molecules, which results in a significant increase in the hydrodynamic size, and thereby, attenuates a rapid renal clearance of PEGylated products [2]. In addition, the steric stabilization that is imparted by the formation of a hydration zone around a PEGylated substance protects the PEGylated product against enzymatic degradation and against the surface binding of certain serum proteins (opsonins) that interact with the immune system [3, 4]. Consequently, PEGylation efficiently evades the recognition of PEGylated products by the mononuclear phagocyte system (MPS), which is an obstacle that has hindered the therapeutic efficacy of many non-PEGylated products.
Glossary of scientific and technical terms in bioengineering and biological engineering
Published in Megh R. Goyal, Scientific and Technical Terms in Bioengineering and Biological Engineering, 2018
PEG is an abbreviation for polyethylene glycol that is a polyether compound with many applications from industrial manufacturing to medicine. The structure of PEG is H-(O-CH2-CH2)n-OH. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular weight.
Translation: Opportunities and Challenges
Published in Sourav Bhattacharjee, Principles of Nanomedicine, 2019
Another point of criticism is the over-reliance on the enhanced permeation and retention (EPR) effect, which has been one of the key motives for rushing anticancer nanoformulations through clinical trials. A detailed discussion of the EPR effect is provided in Chapter 3. In a nutshell, the EPR effect ensures accumulation of nanomedicines in tumors due to the leaky vasculature. The EPR effect does exist, though how much it helps in site-specific delivery in tumors is highly debatable [81–84]. It is known that a significant fraction, sometimes as high as ≥90%, of the administered dose of nanomedicines is filtered by macrophages in the reticuloendothelial system (RES) (liver, spleen, lungs) promptly after administration. Coating of the nanomedicines with opsonin proteins (e.g., collagen and fibronectin) in blood triggers such RES-based entrapment and subsequent clearance from the blood. Hence, only a meager fraction of the administered dose ultimately reached systemic circulation [85–87]. One recent metanalytic review of all the literature published on tumor-specific nanomedicine formulations has argued that only 0.7% of the injected dose (median average) reaches the tumor sites [88]. Even in most promising formulations, this fraction is rarely >5% of the administered dose. Unfortunately, it is simply too low to exert any therapeutic effect despite EPR. For a fruitful translation, capture by the RES has to be addressed. PEGylation has widely been advocated as a strategy to avoid the RES and extend the blood circulation time of the nanomedicines, which is a valid strategy. However, PEGylation is not always an easy technique, while polyethylene glycol (PEG) itself is not a biodegradable polymer [89, 90]. It is known that the metabolism of PEG in the human body is quite slow and can result in acidic products due to enzymatic conversion of its terminal hydroxyls into acid groups. Hence, a PEG overdose is reported to result in acidosis and hypercalcemia [91]. Additionally, PEG provides with an extra layer over the nanoconstructs to meddle with the timely release of the encapsulated drug.
Synthesis and characterization of hybrid nanocarrier layered double hydroxide grafted by polyethylene glycol and gemcitabine
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Xue Li, Shuxin Xu, Haojiang Wang, Anjie Dong
Polyethylene glycol (PEG) is generally utilized as functional polymers for modification of drug delivery carriers [29]. As its dominance, PEG shows regular structure, fine biocompatibility and solubility as well as favorable intermiscibility within amounts of organisms. In addition, the existence of PEG enhances the dispersibility of drug delivery system and gives rise to more effective in vivo circulation. According to the advantages mentioned above, PEG becomes massive popular in many fields, especially in studies of drug delivery system [30, 31]. Cao et al. synthesised PEG-conjugated LDH nanoparticles by introducing phosphonic acid terminated PEG before and after LDH aging to improve the colloidal and biological stability of LDHs for biomedical applications [32]. Gemcitabine (Gemci) is considered to be a sort of widely used anti-cancer drug [33, 34]. Chemically gemcitabine is a nucleoside analog in which the hydrogen atoms on the 2′ carbon of deoxycytidine are replaced by fluorine atoms. As with fluorouracil and other analogues of pyrimidines, the triphosphate analogue of gemcitabine replaces one of the building blocks of nucleic acids. This process arrests tumor growth, leading to cell apoptosis. Gemcitabine is broadly used in treatments of pancreatic cancer, ovarian cancer and breast cancer.Small interfering RNAs (siRNAs) were identified as ribonucleic acids which help in gene silencing and are capable of controlling over-expressed α-syn gene to a normal level. However, the utilization of naked siRNA is limited by its low transfection efficiency and degradability in blood. Moreover, siRNA is not permeable to the blood/brain barrier. Thus, LDH can perform as a vehicle which provides a space where siRNA can intercalate in order to remain activity until the nanocarrier arrives to the focal zone. In our study, we intercalate siRNAs into the interlamellar of LDH to protect siRNAs from the blood environment and realize the function of siRNA on a large degree.
Significance of radiative magnetohydrodynamic flow of suspended PEG based ZrO2 and MgO2 within a conical gap
Published in Waves in Random and Complex Media, 2022
S. Mamatha Upadhya, C. S. K. Raju, K. Vajravelu, Suresh Sathy, Umer Farooq
Polyethylene glycol (PEG) is a water-soluble liquid or waxy solid applied in pharmaceutical and cosmetic preparations, in the production of polyurethane resins PEG is used in industrial processes to suppress foaming, in the manufacture of wetting or emulsifying agents and lubricants.
Bioinks—materials used in printing cells in designed 3D forms
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Dilara Goksu Tamay, Nesrin Hasirci
Poly(ethylene glycol) (PEG) which is also known as poly(ethylene oxide) or poly(oxyethylene), is a synthetic hydrophilic polymer. It can be synthesized as linear, branched or star-shaped and can be easily modified to produce bioinks. It can be activated with the addition of reactive groups so that tunable bioinks can be produced with a wide range of mechanical and rheological properties. These bioinks can withhold cells and can be printed without any damage to cells [125]. PEG is biocompatible and non-immunogenic, and widely used in the preparation of micro or nano carriers for drug delivery with controllable sizes or degradation rates [207,208]. PEG scaffolds are also produced for tissue engineering applications [209,210]. Many drugs were conjugated to PEG via PEGylation process. This increases the therapeutic activity of the drug by increasing the circulation time of in the body and prevents the attack of enzymes [211]. Although PEG is known as non-immunogenic, there are studies showing that there are antibodies which recognize PEG and cause immunogenic response [212,213]. PEG is not biodegradable; however, it can be made biodegradable by copolymerizing with polymers having functional groups such as poly(glycolic acid) (PGA) and poly(lactic acid) [214]. It can be combined with proteins having RGD sequences and be attractive for cells to adhere and proliferate [215]. Hudson et al. blended PEG with gelatin methacrylate (GelMA) which enhanced the cytocompatibility of the scaffold produced [216]. Presence of GelMA increased fibroblast surface binding and spreading as compared to pure PEG hydrogels. Hockaday et al. printed PEGDA-alginate hydrogels with Native anatomic and axisymmetric aortic valve geometries by using different molecular weights (700 or 8000 MW) of PEGDA [217]. They optimized printing conditions and then seeded and cultured porcine aortic valve interstitial cells (PAVIC). In order to optimize printing parameters and determine the effects of extrusion parameters on cell viability, Kang et al. used PEGDA-gelatin bioink as model bioink and PAVIC as model cells were determined [218]. They printed highly viscous hydrogels loaded with high cell concentration. Mechanical strength of PEG is not high, but it can be tailored with the addition of either diacrylate to form PEGDA, or methacrylate to form PEGMA. Acrylate functional groups with unsaturated double bonds can crosslink by free radical reactions via photopolymerization and lead to a high strength material to be used as bioink [219–221]. There is also 4-arm poly(ethylene glycol)-tetra-acrylate (PEGTA) which has high crosslinking density and therefore has high mechanical stability [222]. Wu et al. prepared a bioink from PEGDA and gellan gum which demonstrated superior shear-thinning and recovery properties [53]. The constructs containing BMSCs and MC3T3-E1 were printed as human ear and nose in the natural size and stabilized by UV after printing.