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Journal of Bioactive and Compatible Polymers
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Physico-Chemical and Biological Properties of Monofunctional Hydroxy Teriminating Poly(N-Vinylpyrrolidone) Conjugated Superoxide Dismutase

Paolo Caliceti

Dipartimento di Scienze Farmaceutiche, (Centro di Chimica del Farmaco e dei Prodotti Biologicamente Attivi del CNR), Università di Padova, Via F. Marzolo 5, Padova, Italy

Oddone Schiavon

Dipartimento di Scienze Farmaceutiche, (Centro di Chimica del Farmaco e dei Prodotti Biologicamente Attivi del CNR), Università di Padova, Via F. Marzolo 5, Padova, Italy

Margherita Morpurgo

Dipartimento di Scienze Farmaceutiche, (Centro di Chimica del Farmaco e dei Prodotti Biologicamente Attivi del CNR), Università di Padova, Via F. Marzolo 5, Padova, Italy

Francesco M. Veronese

Dipartimento di Scienze Farmaceutiche, (Centro di Chimica del Farmaco e dei Prodotti Biologicamente Attivi del CNR), Università di Padova, Via F. Marzolo 5, Padova, Italy

Luciana Sartore

Dipartimento di Ingegneria Meccanica, Università di Brescia, Via Branze, Brescia, Italy

Elisabetta Ranucci

Dipartimento di Ingegneria Meccanica, Università di Brescia, Via Branze, Brescia, Italy

Paolo Ferruti

Dipartimento di Ingegneria Meccanica, Università di Brescia, Via Branze, Brescia, Italy

Monofunctional hydroxy-terminated poly(N-vinylpyrrolidone) was obtained by radical polymerization in the presence of isopropoxyethanol for protein surface modification. Superoxide dismutase was modified to various degrees by reaction with PVP-OH activated by 4-nitrophenyl chloroformate with high retention of enzymatic activity. All the polymer-enzyme conjugates showed increased body residence time after intravenous injection in rats with respect to the native enzyme. The residence time depended upon the number of bound polymer chains. PVP was found to affect the pharmacokinetic properties of the enzyme after subcutaneous, intramuscular and intraperitoneal administration. The antigenicity of superoxide dismutase was reduced to one third following modification, while its immunogenicity after intravenous, subcutaneous and intraperitoneal injection totally disappeared. The conjugates exhibited increased solubility in organic solvents and increased stability towards thermal denaturation, whereas changes in the structural properties were observed by circular dichroism measurements.

Journal of Bioactive and Compatible Polymers, Vol. 10, No. 2, 103-120 (1995)
DOI: 10.1177/088391159501000202
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