Improvement of Drug Therapy by Covalent PEG Conjugation: An Overview From a Research Laboratory

Abstract

In the last two decades, efforts focused in the field of drug delivery have made it possible to reach important goals, especially with proteins and peptides. The story of the evolution of this matter is vast and it is difficult to summarize its various aspects in a single review. On the other hand, it could be really interesting to look at the inside story of a typical academic research lab that has dedicated almost all its resources to drug delivery. In our case, an initial interest in the issue of protein conformation stability soon paved the way for a new area of study: the modification of proteins with synthetic polymers. We have seen this technique transformed from a crude and inhomogeneous procedure into a well-recognized and successful approach. This great advance has been possible thanks to the development of dedicated chemical coupling methods and to the better understanding of the behavior of polymers in vivo. In particular, among the several polymers investigated, PEG has became the best polymer for protein modification. Exploiting the unique properties of this polymer, we have conducted several investigations in the field of protein PEGylation and then transferred the acquired know-how to the development of conjugates with low molecular weight drug. This last aspect still presents several unmet needs that are awaiting proper solutions

FDA-approved poly(ethylene glycol)–protein conjugate drugs

“…[4][5][6] The non-ionic, hydrophilic PEG provides a steric shield for conjugates from recognition by the patient's immune system and effectively increases the size of the biomolecule, 7 thereby reducing clearance from the bloodstream. 8 By increasing the half-life of the protein drug, the dosage frequency is reduced. 9 Since most protein drugs need to be injected, this result is significant.…”

Polymers in Drug Delivery—State of the Art and Future Trends

“…Two different approaches for the attachment of PEG to carriers have been investigated. On the one hand, the hydrophilic polymer was covalently attached to the already formulated delivery system 228–231. The other strategy is the synthesis of block or graft copolymers, with the shielding polymer being grafted onto the transport polymer prior to incorporation of the drugs 232, 233.…”

Curtailment of Nephrotoxicity of Polyethylene Glycol via Moringa Oleifera Leaf Extract in Male Rats

“…Polyethylene glycol (PEG) refer to polymers of ethylene oxide [HO-(CH2-CH2-O)n-H], may exist in liquid or lowmelting solid condition based on their molecular weights (Castanho et al, 2009). FDA agree using PEG for medical fields as it was used in topical and anti-microbial cream, and its use could lead to reach to the circulatory system, and thus many lead to an increase in osmolality in the blood, calcium and kidney failure (Cadnapaphornchai et al, 1981;Herold et al, 1989;Pasut & Veronese, 2010). The German Cosmetic, Toiletry, Perfumery and Detergent Association explained many impurities when using PEG in cosmetics for example (dioxin, ethylene, ethylene oxide and heavy metals) (Fruijtier-Pölloth, 2005).…”