title: Synthesis and characterization of poly(2-ethyl 2-oxazoline)-conjugates with proteins and drugs: suitable alternatives to PEG-conjugates?
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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Padua, via Marzolo 5, Padua 35128, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Mero
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pasut
authors.forename: Lisa
authors.initials: L
authors.lastname: Dalla Via
authors.forename: Martin W M
authors.initials: MW
authors.lastname: Fijten
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Schubert
authors.forename: Richard
authors.initials: R
authors.lastname: Hoogenboom
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Veronese
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D002364:Caseins / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry*; D004950:Esterases / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D010080:Oxazoles / Q000008:administration & dosage* / Q000737:chemistry*; D011073:Polyamines; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry*; D014357:Trypsin / Q000737:chemistry
chemical_list: D000964:Antimetabolites, Antineoplastic; D002364:Caseins; D004337:Drug Carriers; D010080:Oxazoles; D011073:Polyamines; D011108:Polymers; C511916:poly(2-ethyl-2-oxazoline); D003561:Cytarabine; D011092:Polyethylene Glycols; D004950:Esterases; D014357:Trypsin; D000581:Amidohydrolases; C019665:amidase