Architectural Modification of Conformal PEG-Bottlebrush Coatings Minimizes Anti-PEG Antigenicity While Preserving Stealth Properties.

Published

Journal Article

Poly(ethylene glycol) (PEG), a linear polymer known for its "stealth" properties, is commonly used to passivate the surface of biomedical implants and devices, and it is conjugated to biologic drugs to improve their pharmacokinetics. However, its antigenicity is a growing concern. Here, the antigenicity of PEG is investigated when assembled in a poly(oligoethylene glycol) methacrylate (POEGMA) "bottlebrush" configuration on a planar surface. Using ethylene glycol (EG) repeat lengths of the POEGMA sidechains as a tunable parameter for optimization, POEGMA brushes with sidechain lengths of two and three EG repeats are identified as the optimal polymer architecture to minimize binding of anti-PEG antibodies (APAs), while retaining resistance to nonspecific binding by bovine serum albumin and cultured cells. Binding of backbone- versus endgroup-selective APAs to POEGMA brushes is further investigated, and finally the antigenicity of POEGMA coatings is assessed against APA-positive clinical plasma samples. These results are applied toward fabricating immunoassays on POEGMA surfaces with minimal reactivity toward APAs while retaining a low limit-of-detection for the analyte. Taken together, these results offer useful design concepts to reduce the antigenicity of polymer brush-based surface coatings used in applications involving human or animal matrices.

Full Text

Duke Authors

Cited Authors

  • Joh, DY; Zimmers, Z; Avlani, M; Heggestad, JT; Aydin, HB; Ganson, N; Kumar, S; Fontes, CM; Achar, RK; Hershfield, MS; Hucknall, AM; Chilkoti, A

Published Date

  • April 2019

Published In

Volume / Issue

  • 8 / 8

Start / End Page

  • e1801177 -

PubMed ID

  • 30908902

Pubmed Central ID

  • 30908902

Electronic International Standard Serial Number (EISSN)

  • 2192-2659

Digital Object Identifier (DOI)

  • 10.1002/adhm.201801177

Language

  • eng

Conference Location

  • Germany