Questioning the use of PEGylation for drug delivery

Abstract

Polyethylene glycol (PEG) is widely utilized in drug delivery and nanotechnology due to its reported “stealth” properties and biocompatibility. It is generally thought that PEGylation allows particulate delivery systems and biomaterials to evade the immune system and thereby prolong circulation lifetimes. However, numerous studies over the past decade have demonstrated that PEGylation causes significant reductions in drug delivery, including enhanced serum protein binding, reduced uptake by target cells, and the elicitation of an immune response that facilitates clearance in vivo. This report reviews some of the extensive literature documenting the detrimental effects of PEGylation, and thereby questions the wisdom behind employing this strategy in drug development.

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Acknowledgments

Some of the work discussed here was supported by grant no. 1 RO1EB016378 and no. 1 RO1GM093287 to TJA.

Conflict of interest

The authors are academic researchers with no financial interest in any of the work described in this manuscript.

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Correspondence to Thomas J. Anchordoquy.

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Verhoef, J.J.F., Anchordoquy, T.J. Questioning the use of PEGylation for drug delivery. Drug Deliv. and Transl. Res. 3, 499–503 (2013). https://doi.org/10.1007/s13346-013-0176-5

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Keywords

  • Polyethylene glycol
  • PEG
  • Transfection
  • DNA
  • RNA
  • Drug delivery
  • Immunogenicity
  • Stealth