Drug and protein delivery by polymer conjugation

Grigoletto, Antonella; Maso, Katia; Mero, Anna; Rosato, Antonio; Schiavon, Oddone; Pasut, Gianfranco

doi:10.1016/j.jddst.2015.08.006

Cited by 37 publications

(21 citation statements)

References 111 publications

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“…PEG has been used as an excipient in many pharmaceuticals, cosmetics, and consumer products for decades, and as a conjugate with biologicals (i.e., PEGylation) since 1990 [ 1 , 2 , 3 , 4 , 5 ]. Currently, there are 20 PEGylated therapies with diverse indications in clinical use in the United States and Europe [ 1 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Polyethylene Glycol Exposure with Antihemophilic Factor (Recombinant), PEGylated (rurioctocog alfa pegol) and Other Therapies Indicated for the Pediatric Population: History and Safety

Stidl¹,

Denne

Goldstine

et al. 2018

Pharmaceuticals

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Polyethylene glycol (PEG) is an inert, water soluble polymer, used for decades in pharmaceuticals. Although PEG is considered safe, concerns persist about the potential adverse effects of long-term exposure to PEG-containing therapies, specifically in children, following the introduction of PEGylated recombinant factor products used for the treatment of hemophilia. Given the absence of long-term surveillance data, and to evaluate the potential risk, we estimated PEG exposure in the pediatric population receiving PEGylated therapies with pediatric indications administered intravenously or intramuscularly. We used a range of pediatric weights and doses based on prescribing information (PI) or treatment guidelines. PIs and reporting websites were searched for information about adverse events (AEs). For a child weighing 50 kg on the highest prophylactic dose of a FVIII product, the range of total PEG exposure was 40–21,840 mg/year; for factor IX (FIX) products, the range was 13–1342 mg/year; and for other products, the range was 383–26,743 mg/year, primarily as a derivative excipient. No AE patterns attributable to PEG were found for any of these products, including potential renal, neurological, or hepatic AEs. Our analyses suggest the pediatric population has had substantial exposure to PEG for several decades, with no evidence of adverse consequences.

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Section: Introductionmentioning

confidence: 99%

Polyethylene Glycol Exposure with Antihemophilic Factor (Recombinant), PEGylated (rurioctocog alfa pegol) and Other Therapies Indicated for the Pediatric Population: History and Safety

Stidl¹,

Denne

Goldstine

et al. 2018

Pharmaceuticals

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“…We recently completed the enzymatic set by obtaining recombinant Uox from the same source ( 17 ). To improve the bioavailability of Dr Uox, Dr Urah and Dr Urad we used chemical conjugation with polyethylene glycol (PEG), a well-known technology that has been used to prolong half-life of biotech-drugs ( 18 , 19 ). PEG is a biocompatible polymer that can be covalently conjugated to proteins to improve their biocompatibility and reduce immunological recognition and clearance ( 19 – 23 ).…”

Section: Introductionmentioning

confidence: 99%

A Trivalent Enzymatic System for Uricolytic Therapy of HPRT Deficiency and Lesch-Nyhan Disease

et al. 2017

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PurposeBecause of the evolutionary loss of the uricolytic pathway, humans accumulate poorly soluble urate as the final product of purine catabolism. Restoration of uricolysis through enzyme therapy is a promising treatment for severe hyperuricemia caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT). To this end, we studied the effect of PEG conjugation on the activity and stability of the enzymatic complement required for conversion of urate into the more soluble (S)-allantoin.MethodsWe produced in recombinant form three zebrafish enzymes required in the uricolytic pathway. We carried out a systematic study of the effect of PEGylation on the function and stability of the three enzymes by varying PEG length, chemistry and degree of conjugation. We assayed in vitro the uricolytic activity of the PEGylated enzymatic triad.ResultsWe defined conditions that allow PEGylated enzymes to retain native-like enzymatic activity even after lyophilization or prolonged storage. A combination of the three enzymes in an appropriate ratio allowed efficient conversion of urate to (S)-allantoin with no accumulation of intermediate metabolites.ConclusionsPharmaceutical restoration of the uricolytic pathway is a viable approach for the treatment of severe hyperuricemia.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-017-2167-6) contains supplementary material, which is available to authorized users.

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“…Due to its biocompatibility and proteinrepellent properties, PEG is frequently used in many biomedical applications including bioconjugation and drug delivery (Veronese and Pasut, 2005;Cheng et al, 2007;Bruni et al, 2017). Bioconjugation with PEG, also known as PEGylation, is the formation of a covalent bond between therapeutic molecules and PEG in order to extend circulation half-life of therapeutics, thus reducing the frequency of dosing while maintaining the pharmaceutical effects (Grigoletto et al, 2016).…”

Section: Pegylationmentioning

confidence: 99%

Nanosized Delivery Systems for Therapeutic Proteins: Clinically Validated Technologies and Advanced Development Strategies

Moncalvo

Espinoza

Cellesi

2020

Front. Bioeng. Biotechnol.

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The impact of protein therapeutics in healthcare is steadily increasing, due to advancements in the field of biotechnology and a deeper understanding of several pathologies. However, their safety and efficacy are often limited by instability, short half-life and immunogenicity. Nanodelivery systems are currently being investigated for overcoming these limitations and include covalent attachment of biocompatible polymers (PEG and other synthetic or naturally derived macromolecules) as well as protein nanoencapsulation in colloidal systems (liposomes and other lipid or polymeric nanocarriers). Such strategies have the potential to develop next-generation protein therapeutics. Herein, we review recent research progresses on these nanodelivery approaches, as well as future directions and challenges.

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Drug and protein delivery by polymer conjugation

Cited by 37 publications

References 111 publications

Polyethylene Glycol Exposure with Antihemophilic Factor (Recombinant), PEGylated (rurioctocog alfa pegol) and Other Therapies Indicated for the Pediatric Population: History and Safety

Polyethylene Glycol Exposure with Antihemophilic Factor (Recombinant), PEGylated (rurioctocog alfa pegol) and Other Therapies Indicated for the Pediatric Population: History and Safety

A Trivalent Enzymatic System for Uricolytic Therapy of HPRT Deficiency and Lesch-Nyhan Disease

Nanosized Delivery Systems for Therapeutic Proteins: Clinically Validated Technologies and Advanced Development Strategies

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