Recent advances in the bioanalytical methods of polyethylene glycols and PEGylated pharmaceuticals

Abstract

Polyethylene glycols are synthetic polymers composed of repeating oxyethylene subunits, which have been known for non-toxic, non-immunogenic, non-antigenic, good solubility in water and therefore approved for pharmaceutical applications. Recently, attachment or amalgamation of polyethylene glycols to therapeutic small molecules, peptides, proteins, or nanoparticles has become a mature technology for the sake of improving their pharmacokinetic and pharmacological profiles, also referred to as PEGylation. By comparison, there are only a few PEGylated pharmaceuticals have been registered for further clinical trials and even less was approved for marketing. High failure rate of PEGylated pharmaceuticals in pre-clinical and clinical trials could be majorly attributed to their unclear pharmacokinetic behaviors. Therefore, the in vivo fate of the PEGylated pharmaceuticals for the various routes of administration needs to be thoroughly investigated An accurate in vivo pharmacological study thereof highly depends on the precise detection of polyethylene glycols as well as their fragments in biological matrixes. The goal of this review is to highlight the analytical methods that were developed and applied to evaluate the polyethylene glycols in pharmaceutical ingredients and excipients, which bring us closer to bridging

Recent developments in capillary and microchip electroseparations of peptides (2019–mid 2021)

“…In most of the above applications of (bio) synthetic or naturally isolated peptides, CE and CEC can be used as sensitive control methods to assess the peptide purity. As shown in some previous [107,199] and recent [200][201][202] reviews, CE methods provide fast and accurate qualitative and quantitative information about purity of peptide drugs. Further, some recent applications of CE methods to peptide analyses will be presented, in addition to those shown in the previous sections.…”

Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery

“…PEGylation has been proposed for virtually every one of the nanoparticle types described in the previous section. This includes PEGylated carbon nanotubes (Pennetta et al, 2020), gold nanoparticles (Oroskar et al, 2016;Lin et al, 2017;Sun et al, 2019), silver nanoparticle (Pinzaru et al, 2018), silver-graphene nanoparticles (Habiba et al, 2015), nano-graphene (Zhang et al, 2014;Zhang Z. et al, 2020;Mahdavi et al, 2020), lipid micelles (Arleth et al, 2005;Viitala et al, 2019; Figure 6D), nanodiscs (Zhang et al, 2014), dendrimers (Kojima et al, 2000;Larson, 2009, 2011;Zhang et al, 2014), and a topic covered comprehensively in our previous review, liposomes (Bunker et al, 2016; Figures 6A,C).…”

“…All of these structures can have their properties fine-tuned by being functionalized to polymers or smaller molecules themselves, in the same fashion as described above for the drug molecule itself. For example functionalizing poly(ethylene glycol) (PEG) (Israelachvili, 1997), a process known as "PEGylation" (Bunker, 2012(Bunker, , 2015Pasut and Veronese, 2012;Bunker et al, 2016;Zhang Z. et al, 2020) has been proposed and studied for virtually all of these nanoparticle forms and, as we will discuss in further detail in the next section, alternate polymers to PEG are under investigation. The extent to which these systems can be fine-tuned is limitless, for example formulation alteration of liposomes offer an extremely broad pallet (Bunker et al, 2016;.…”

Nanodrugs Targeting T Cells in Tumor Therapy

“…Polymer-protein conjugates that are applied in cancer treatment are mainly PEGylated proteins as PEGylation effectively protects proteins from degradation and improves drug distribution ( 131 ). The PEGylated liposomal formulation of doxorubicin, Doxil, was the first nano-medicine approved by the FDA for ovarian cancer (OC), acquired immune deficiency syndrome (AIDS)-related Kaposi´s sarcoma and multiple myeloma ( 98 ).…”