The synthesis of a series of novel, water-soluble poly(organophosphazenes) prepared via living cationic polymerization is presented. The degradation profiles of the polyphosphazenes prepared are analyzed by GPC, 31P NMR spectroscopy, and UV-Vis spectroscopy in aqueous media and show tunable degradation rates ranging from days to months, adjusted by subtle changes to the chemical structure of the polyphosphazene. Furthermore, it is observed that these polymers demonstrate a pH-promoted hydrolytic degradation behavior, with a remarkably faster rate of degradation at lower pH values. These degradable, water soluble polymers with controlled molecular weights and structures could be of significant interest for use in aqueous biomedical applications, such as polymer therapeutics, in which biological clearance is a requirement and in this context cell viability tests are described which show the non-toxic nature of the polymers as well as their degradation intermediates and products.

Institute of Cancer Research and Comprehensive Cancer Center of the Medical University of Vienna Medical University of Vienna Borschkegasse 8a 1090 Vienna Austria

Institute of Cancer Research and Comprehensive Cancer Center of the Medical University of Vienna Medical University of Vienna Borschkegasse 8a 1090 Vienna Austria ; Research and Platform Translational Cancer Therapy Research Vienna Austria

Institute of Organic Chemistry Johannes Kepler University Linz Altenberger Street 69 4040 Linz Austria ; Faculty of Science University of South Bohemia Branišovská 31 370 05 České Budějovice Czech Republic

Institute of Polymer Chemistry Johannes Kepler University Linz Welser Street 42 4060 Leonding Austria

See more in PubMed

Ulery BD, Nair LS, Laurencin CT. J. Polym. Sci., Part B: Polym. Phys. 2011;49:832–864. PubMed PMC

Nicolas J, Mura S, Brambilla D, Mackiewicz N, Couvreur P. Chem. Soc. Rev. 2013;42:1147–1235. PubMed

Schacht E, Vandorpe J, Dejardin S, Lemmouchi Y, Seymour L. Biotechnol. Bioeng. 1996;52:102–108. PubMed

Haag R, Kratz F. Angew. Chem. Int. Ed. 2006;45:1198–1215. PubMed

Duncan R. Nat. Rev. Cancer. 2006;6:688–701. PubMed

Etrych T, Jelínková M, Ríhová B, Ulrbich KK. J. Controlled Release. 2001;73:89–102. PubMed

Ulbrich K, Etrych T, Chytil P, Jelínková M, Ríhová B. J. Controlled Release. 2003;87:33–47. PubMed

Duncan R. Nat. Rev. Drug Discovery. 2003;2:347–360. PubMed

Markovsky E, Baabur-Cohen H, Eldar-Boock A, Omer L, Tiram G, Ferber S, Ofek P, Polyak D, Scomparin A, Satchi-Fainaro R. J. Controlled Release. 2012;161:446–460. PubMed

Shenoi RA, Narayanannair JK, Hamilton JL, Lai BFL, Horte S, Kainthan RK, Varghese JP, Rajeev KG, Manoharan M, Kizhakkedathu JN. J. Am. Chem. Soc. 2012;134:14945–14957. PubMed

Duncan R, Vicent MJ. Adv. Drug Delivery Rev. 2010;62:272–282. PubMed

van der Poll DG, Kieler-Ferguson HM, Floyd WC, Guillaudeu SJ, Jerger K, Szoka FC, Fréchet JM. Bioconjugate Chem. 2010;21:764–773. PubMed PMC

Zhang S, Li A, Zou J, Lin LY, Wooley KL. ACS Macro Lett. 2012;1:328–333. PubMed PMC

Teasdale I, Brüggemann O. Polymers. 2013;5:161–187. PubMed PMC

Lakshmi S, Katti DS, Laurencin CT. Adv. Drug Delivery Rev. 2003;55:467–482. PubMed

Allcock HR. Soft Matter. 2012;8:7521–7532. PubMed PMC

Allcock HR. Chemistry and Applications of Polyphosphazenes. 1st. Hoboken: Wiley; 2003.

Ren N, Huang X-J, Huang X, Qian Y-C, Wang C, Xu Z-K. J. Polym. Sci., Part A: Polym. Chem. 2012;50:3149–3157.

Teasdale I, Wilfert S, Nischang I, Brüggemann O. Polym. Chem. 2011;2:828–834.

Kumbar SG, Bhattacharyya S, Nukavarapu SP. Khan YM, Nair LS, Laurencin CT. J. Inorg. Organomet. Polym. Mater. 2006;16:365–385.

Allcock HR, Fuller TJ, Mack DP, Matsumara K, Smeltz KM. Macromolecules. 1977;10:824–830.

Allcock HR, Pucher SR, Scopelianos AG. Macromolecules. 1994;27:1071–1075.

Andrianov AK, Marin A. Biomacromolecules. 2006;7:1581–1586. PubMed

Morozowich NL, Weikel AL, Nichol JL, Chen C, Nair LS, Laurencin CT, Allcock HR. Macromolecules. 2011;44:1355–1364.

Laurencin CT, Norman ME, Elgendy HM, El-Amin SF, Allcock HR, Pucher SR, Ambrosio AA. J. Biomed. Mater. Res. 1993;27:963–973. PubMed

Allcock HR, Pucher SR. Macromolecules. 1991;24:23–34.

Allcock HR, Kwon S. Macromolecules. 1988;21:1980–1985.

Andrianov AK, Marin A, Peterson P. Macromolecules. 2005;38:7972–7976.

Crommen JHL, Schacht EH, Mense EHG. Biomaterials. 1992;13:511–520. PubMed

Crommen JHL, Schacht EH, Mense EHG. Biomaterials. 1992;13:601–611. PubMed

Allcock HR, Morozowich NL. Polym. Chem. 2012;3:578–590.

Allcock HR, Crane CA, Morrissey CT, Nelson JM, Reeves SD, Honeyman CH, Manners I. Macromolecules. 1996;29:7740–7747.

Blackstone V, Lough AJ, Murray M, Manners I. J. Am. Chem. Soc. 2009;131:3658–3667. PubMed

Nichol JL, Morozowich NL, Allcock HR. Polym. Chem. 2013;4:600–606.

Tian Z, Zhang Y, Liu X, Chen C, Guiltinan MJ, Allcock HR. Polym. Chem. 2013;4:1826–1835.

Wilfert S, Iturmendi A, Henke H, Brüggemann O, Teasdale I. Macromol. Symp. in press. PubMed PMC

Wang B, Rivard E, Manners I. Inorg. Chem. 2002;41:1690–1691. PubMed

Paulsdorf J, Burjanadze M, Hagelschur K, Wiemhöfer H. Solid State Ionics. 2004;169:25–33.

Peddada LY, Harris NK, Devore DI, Roth CM. J. Controlled Release. 2009;140:134–140. PubMed PMC

Henke H, Wilfert S, Iturmendi A, Brüggemann O, Teasdale I. J. Polym. Sci., Part A: Polym. Chem. 2013;51:4467–4473. PubMed PMC

Gabler DG, Haw JF. Macromolecules. 1991;24:4218–4220.

Andrianov AK. Polyphosphazenes for Biomedical Applications. 1st. Hoboken: Wiley; 2009. pp. 25–26. ed.;, Chapter 2.

Allcock HR, Pucher SR, Scopelianos AG. Macromolecules. 1994;27:1–4.

Allcock HR, Maher AE, Ambler CM. Macromolecules. 2003;36:5566–5572.

Zhang S, Wang H, Shen Y, Zhang F, Seetho K, Zou J, Taylor J-SA, Dove AP, Wooley KL. Macromolecules. 2013;46:5141–5149. PubMed PMC

DeCollibus DP, Marin A, Andrianov AK. Biomacromolecules. 2010;11:2033–2038. PubMed

Carriedo GA, García Alonso FJ, García Álvarez JL, Presa Soto A, Tarazona MP, Laguna MTR, Marcelo G, Mendicuti F, Saiz E. Macromolecules. 2008;41:8483–8490.

Allcock HR, Fuller TJ, Matsumura K. Inorg. Chem. 1982;21:515–521.