Synthesis and characterization of poly(2-ethyl 2-oxazoline)-conjugates with proteins and drugs: Suitable alternatives to PEG-conjugates?
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Mero, Anna; Pasut, Gianfranco; Via, Lisa Dalla; Fijten, Martin W. M.; Schubert, Ulrich S.; Hoogenboom, Richard; Veronese, Francesco M.
- Abstract:
- Poly(2-ethyl-2-oxazoline) (POZ) was synthesized by living cationic ring-opening polymerization under microwave irradiation yielding
polymers with low polydispersity indices (PDI, 1.15). The polymerization was quenched with sodium carbonate yielding a hydroxyl end-group
with a high degree of functionality. The hydroxyl group was converted to carboxylate and the polymer was purified by ionic exchange
chromatography. Following activation to succinimidyl ester, POZ-conjugates to high and low molecular weight biomolecules, trypsin and Ara-C,
were obtained. The properties of the conjugates were compared to those of the corresponding conjugates with poly(ethylene glycol) (PEG) of
similar size. The coupling of POZ to trypsin did not affect the enzymatic activity towards low mass substrates but, on the contrary, reduced the
activity on the higher mass ones. Furthermore, the POZ–protein conjugates showed hydrodynamic volumes and protein rejecting properties
similar to those of PEG-conjugates. Similarly, the POZ–Ara-C conjugate revealed a drug release profile, stability towards the degrading enzyme
cytidine deaminase and in vitro cytotoxicity comparable to what has already been described for the PEG derivative. These data support the
potential of POZ as a versatile alternative to the well-known and widely used PEG for protein and drug conjugation and delivery.
- Year:
- 2008
- Type of Publication:
- Article
- Journal:
- Journal of Controlled Release
- Volume:
- 125
- Pages:
- 87 - 95