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VNPs as Tools for Nanomedicine
Published in Nicole F Steinmetz, Marianne Manchester, Viral Nanoparticles, 2019
Nicole F Steinmetz, Marianne Manchester
Polythylene glycol (Fig. 8.1) is a non-charged, highly hydrophilic polymer. PEG is non-toxic and has been approved for use in humans by the U.S. Food & Drug Administration (FDA). Increasingly being used for pharmaceuticals and other biomedical applications, PEGylation efficiently reduces or blocks biospecific interactions, increases solubility and stability, increases plasma circulation time, and reduces immunogenicity. PEGylation has been applied to a variety of nanomaterials including liposomes, carbon nanotubes, and dendrimers (reviewed in Harris & Chess, 2003; Roberts et al., 2002; Wattendorf & Merkle, 2008). Structure of polyethylene glycol (PEG).
Anti-PEG Immunity Against PEGylated Therapeutics
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
Polyethylene glycol (PEG) is one of the most widely used “stealth” polymers in the field of pharmaceutics for protein and drug carriers [1, 2]. PEGylation is the covalent coupling of polyethylene glycol (PEG) to peptides and proteins in order to significantly extend their biological half-life, reduce toxicity, and mask both humoral and cellular immunogenicity while sustaining therapeutic effectiveness [3, 4]. The covalent attachment of PEG to liposomes and colloidal nanocarriers can also suppress protein adsorption onto their surfaces, thereby rendering them invisible to the cells of the mononuclear phagocyte system (MPS), which extends their circulation time in the body and improves their overall therapeutic efficacy [5–7].
Proteins and Proteomics
Published in Firdos Alam Khan, Biotechnology Fundamentals, 2020
PEGylation is the process of covalent attachment of poly(ethylene glycol) (PEG) polymer chains to another molecule, normally a drug or therapeutic protein. PEGylation is routinely achieved by incubation of a reactive derivative of PEG with the target macromolecule. The covalent attachment of PEG to a drug or therapeutic protein can “mask” the agent of the host’s immune system (reduced immunogenicity and antigenicity) and increase the hydrodynamic size (size in solution) of the agent, which prolongs its circulatory time by reducing renal clearance. PEGylation can also provide water solubility to hydrophobic drugs and proteins.
Cell membrane-cloaked bioinspired nanoparticles: a novel strategy for breast cancer therapy
Published in Journal of Dispersion Science and Technology, 2023
Anuja Muley, Abhijeet Kulkarni, Prajakta Mahale, Vishal Gulecha
Nanotechnology given another stage for nano-scale drug delivery. A few ideal qualities of nanoformulations are that it ought to be monodisperse, biocompatible, nontoxic, significantly stable and can be scale up at industry level [5]. Different nanoformulations investigated till date in breast cancer are liposomes [6], nanoparticles [7], carbon nanotube [8], polymeric micelles [9], polymerosome [10], solid lipid nanoparticles [11], dendrimers [12], cyclodextrin complexes [13]. Nanoparticles give advantages over other dosage form like tunable size, higher stability, easy surface modification, variety in the material, easy method of preparations, and variety in drug routes. Organic and inorganic nanoparticle systems can be fabricated from different materials, such as lipids, polymers, ceramic, and metals [14]. A PEGylation strategy is investigated as a method of decreasing opsonization of NPs through stearic hindrance and maximizing residence time [15]. Despite this, some drawbacks associated with PEGylation include decreased intracellular uptake, lower transfection efficiency, anti-PEG antibody production, etc [16].
Toxicity and immunogenicity concerns related to PEGylated-micelle carrier systems: a review
Published in Science and Technology of Advanced Materials, 2019
Kouichi Shiraishi, Masayuki Yokoyama
PEGs form a hydrated PEG layer, which resists adsorption of serum proteins and phagocytic uptake. This effect has been called a stealth effect. The stealth effect of PEGylation improves the blood circulation half-lives of biopharmaceuticals, as well as nanoparticles. In recent studies, we and other researchers have shown importance of PEGylation density onto nanoparticles’ surface, and they revealed a ‘dense brush’ conformation is required to suppress phagocytic uptake in vitro and to exhibit long-blood circulation in vivo (Figure 1) [14–18]. These features of PEGylation have led to a new era for developments in biopharmaceuticals and drug carriers. Abuchowski et al. assessed the conjugation of PEG onto proteins, such as bovine serum albumin (BSA) and liver catalase, and claimed that PEGylated BSA improved blood circulation half-lives and elicited antibodies against neither PEG-BSA nor BSA [19]. The results indicate high potency of PEGylation for biopharmaceuticals. PEGylation onto liposomes (PEG-liposomes) exhibited less accumulation in the liver and spleen than did non-PEGylated counterparts [20]. Stealth PEG-liposomes exhibited long blood circulation half-lives. Although PEG-liposomal systems exhibited the stealth effect, the first and only FDA approved PEGylated liposomal drug, CAELYXTM/Doxil is a cytotoxic doxorubicin-loaded PEG-liposome system [21].
PEGYLATION: an important approach for novel drug delivery system
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Deepa Yadav, Hitesh Kumar Dewangan
PEGylation is the attachment of PEG molecule to one more molecule like protein or peptide to enhance the medical value of formulation. In another term, it is a method of covalent addition of PEG polymer chains to one more molecule. Covalent attachment is responsible for decreasing immunogenicity and antigenicity. PEGylation was initially introduced by Davis and Abuchowski in 1970 on behalf of albumin and catalase alteration, after this, the procedure of PEGylation has been residential extremely [1–6]. PEGylation is the alteration of protein, peptide, and non-peptide molecules through the addition of PEG molecules. Polyethylene glycol is poison less, non-immunogenic, non-antigenic in nature, it is extremely water-soluble. PEGylated formulations have numerous benefits: an extended residence in the body, decrease degradation via metabolic enzymes, a decrease of protein elimination [7]. PEGylation shows various benefits over non-PEGylated products. It is responsible for enhancing the therapeutic potential of drugs by increasing its circulation time. PEGylation decreases the immunogenicity and antigenicity of drugs thus it is also responsible for the stability of drugs. Today there are several approved PEGylated pharmaceutical products available in the market and they play a very important role in the drug delivery system. It is also helpful in increasing the hydrodynamic size of drugs. PEGylation prolongs the circulatory time of drugs by dropping its renal clearance [8]. Several examples are given in which PEGylation is done by enzyme catalysis reactions such as transglutaminase. It is also done by the alkylation process [9, 10]. This paper explains the concept of PEGylation. It represents the benefit of PEGylated drugs. PEGylation is beneficial for the enhancement of the circulation time of drugs that finally increases the therapeutic efficacy of the drug.