Packing density of the PEG-shell in PEG-albumins: PEGylation induced viscosity and COP are inverse correlate of packing density

K. Ananda, Belur N. Manjula, Fantao Meng, Vivek N. Acharya, Marcos Intaglietta, Seetharama A. Acharya

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

PEG-Alb represents a new class of low viscogenic plasma expanders that achieve super perfusion in vivo by mimicking the vasodilatory influence of high viscogenic plasma expanders. PEGylation-engineered structure of PEG albumin can be envisaged as a deformable molecular domain around the rigid central protein core. The correlation between the structure of PEG-shell in terms of packing of the PEG inside the PEG shell and PEGylation induced plasma expander (PE)-like properties of albumin has been investigated as a function of the number and length of the PEG-chain. The increase in molecular radius of albumin on PEGylation is non-linear as a function of the number of PEG chains conjugated. The packing density of PEG within the PEG-shell is an inverse correlate of PEG-chain size; i.e. the shorter chains pack more compactly than the longer ones. The PEGylation induced increase in the viscosity and COP of albumin is an exponential correlation of the number of ethylene oxide units (-CH2-CH2-O-) conjugated and is also a function of the PEG-chain length. At equivalence of PEG mass conjugated, the viscosity and COP of PEG-albumin adducts correlate inversely with packing density of PEG. All PEGylated albumins are not equivalent on the basis of total PEG mass conjugated. Accordingly, the structure of PEG albumin and its solution properties can be engineered to optimize a given total PEG mass for the application of PEG albumin as a resuscitation fluid. The extension arms minimize the influence of PEG shell on the structure of the protein core. We speculate that EAF-PEGylation is a preferable platform for PEGylation of protein therapeutics and is expected to generate products with better therapeutic efficacy.

Original languageEnglish (US)
Pages (from-to)14-27
Number of pages14
JournalArtificial Cells, Blood Substitutes, and Biotechnology
Volume40
Issue number1-2
DOIs
StatePublished - Feb 1 2012

Keywords

  • Microcirculation
  • PEGylated albumin
  • Plasma expanders
  • Supra perfusion

ASJC Scopus subject areas

  • Biotechnology
  • Biomedical Engineering

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