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Cited by 432

The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.

Polyoxazoline: Chemistry, Properties, and Applications in Drug Delivery

Viegas, Tacey X., Bentley, Michael D., Harris, J. Milton, Fang, Zhihao, Yoon, Kunsang, Dizman, Bekir, Weimer, Rebecca, Mero, Anna, Pasut, Gianfranco, Veronese, Francesco M.·2011·Bioconjugate Chemistry
DOI 10.1021/bc200049d
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Abstract

Polyoxazoline polymers with methyl (PMOZ), ethyl (PEOZ), and propyl (PPOZ) side chains were prepared by the living cationic polymerization method and purified by ion-exchange chromatography. The following properties of polyoxazoline (POZ) were measured: apparent hydrodynamic radius by aqueous size-exclusion chromatography, relative lipophilicity by reverse-phase chromatography, and viscosity by cone-plate viscometry. The PEOZ polymers of different molecular weights were first functionalized and then conjugated to model biomolecules such as bovine serum albumin, catalase, ribonuclease, uricase, and insulin. The conjugates of catalase, uricase, and ribonuclease were tested for in vitro activity using substrate-specific reaction methods. The conjugates of insulin were tested for glucose lowering activity by injection to naïve Sprague-Dawley rats. The conjugates of BSA were injected into New Zealand white rabbits and serum samples were collected periodically and tested for antibodies to BSA. The safety of POZ was also determined by acute and chronic dosing to rats. The results showed that linear polymers of POZ with molecular weights of 1 to 40 kDa can easily be made with polydispersity values below 1.10. Chromatography results showed that PMOZ and PEOZ have a hydrodynamic volume slightly lower than PEG; PEOZ is more lipophilic than PMOZ and PEG; and PEOZ is significantly less viscous than PEG especially at the higher molecular weights. When PEOZ was attached to the enzymes catalase, ribonuclease, and uricase, the in vitro activity of the resultant bioconjugates depended on the extent of protein modification. POZ conjugates of insulin lowered blood glucose levels for a period of 8 h when compared to 2 h for insulin alone. PEOZ, like PEG, was also able to successfully attenuate the immunogenic properties of BSA. The POZ polymers (10 and 20 kDa) are safe when administered intravenously to rats, and the maximum tolerated dose (MTD) was greater than 2 g/kg. Blood counts, serum chemistry, organ weights, and the histopathology of key organs were normal. These results conclude that POZ has the desired drug delivery properties for a new biopolymer.

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Metadata

Authors
Viegas, T. X., Bentley, M. D., Harris, J. M., Fang, Z., Yoon, K., Dizman, B., Weimer, R., Mero, A., Pasut, G., & Veronese, F. M.
Venue
Bioconjugate Chemistry
Publisher
American Chemical Society (ACS)
Published
2011-04-20
Volume
22
Issue
5
Pages
976-986
ISSN
  • 1043-1802 (ISSN-L)
  • 1520-4812
DOI
10.1021/bc200049d
OpenAlex
W2317610963
Cited by
432
References
32
FWCI
9.88
Type
journal article
Language
en
Open access
closed

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