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Journal of Bioactive and Compatible Polymers
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Branched and Linear Poly(Ethylene Glycol): Influence of the Polymer Structure on Enzymological, Pharmacokinetic, and Immunological Properties of Protein Conjugates

Francesco M. Veronese

Department of Pharmaceutical Sciences, Centro di Studio di Chimica del Farmaco e dei Prodotti, Biologicamente Attivi del CNR, University of Padova, Via F Marzolo, 5, 35131 Padova, Italy

Paolo Caliceti

Department of Pharmaceutical Sciences, Centro di Studio di Chimica del Farmaco e dei Prodotti, Biologicamente Attivi del CNR, University of Padova, Via F Marzolo, 5, 35131 Padova, Italy

Oddone Schiavon

Department of Pharmaceutical Sciences, Centro di Studio di Chimica del Farmaco e dei Prodotti, Biologicamente Attivi del CNR, University of Padova, Via F Marzolo, 5, 35131 Padova, Italy

Linear and branched poly(ethylene glycol)s, with similar molecular weights, were conjugated with uricase and asparaginase, and an investigation of enzymological, immunological, and pharmacokinetic properties of the conjugates was carried out. It was found that the steric hindrance of the branched polymer has a relevant role in determining the biological properties of the conjugates. Conjugations with branched polymers inactivate the enzyme less than the linear ones. Compared to the native and the linear polymer conjugate counterparts the branched polymer derivatives: (1) are more stable to proteolysis by elastase, pronase, and trypsin, (2) stay longer in the blood with increased systemic availability after intravenous administration in mice, and (3) give rise to lower levels of antinative enzyme antibodies after immunization. These data are consistent with a greater surface area of protein covered by the branched PEG.

Journal of Bioactive and Compatible Polymers, Vol. 12, No. 3, 196-207 (1997)
DOI: 10.1177/088391159701200303
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