Biomacromolecules
ARTICLE
profiles of the solubilized dye determined at acidic pH have
shown that the two copolymers have good potential for the
controlled release of hydrophobic drug molecules.
(2) Nakamura, T.; Nagasaki, Y.; Kataoka, K. Bioconjugate Chem.
1998, 9, 300–303.
(3) Koyama, Y.; Ishikawa, M.; Iwamoto, M.; Kojima, S. J. Controlled
Release 1992, 22, 253–261.
(4) Cammas, S.; Suzuki, K.; Sone, C.; Sakurai, Y.; Kataoka, K.;
Okano, T. J. Controlled Release 1997, 48, 157–164.
(5) Chung, J. E.; Yokoyama, M.; Okano, T. J. Controlled Release
2000, 65, 93–103.
(6) Engin, K.; Leeper, D. B.; Cater, J. R.; Thistlethwaite, A. J.;
Tupchong, L.; McFarlane, J. D. Int. J. Hypertherm. 1995, 11, 211–
216.
(7) van Sluis, R.; Bhujwalla, Z. M.; Ballerteros, P.; Alverez, J.; Cerdan,
S.; Galons, J. P.; Gillies, R. J. Magn. Reson. Med. 1999, 41, 743–750.
(8) Ojugo, A. S. E.; Mesheehy, P M. J.; McIntyre, D. J. O.; McCoy,
C.; Stubbs, M.; Leach, M. O.; Judson, I. R.; Griffiths, J. R. NMR Biomed.
1999, 12, 495–504.
(9) Calderon, M.; Quadir, M. A; Strumia, M.; Haag, R. Biochimie
2010, 92, 1242–1251.
(10) Gillies, E. R.; Frechet, J. M. J. Bioconjugate Chem. 2005,
16, 361–368.
(11) Haag, R. Angew. Chem., Int. Ed. 2004, 43, 278–282.
(12) Haag, R.; Kratz, F. Angew. Chem., Int. Ed. 2006, 45, 1198–1215.
(13) Gillies, E. R.; Frechet, J. M. J. Pure Appl. Chem. 2004,
76, 1295–1307.
(14) Yoo, H. S.; Lee, E. A.; Park, T. G. J. Controlled Release 2002,
82, 17–27.
’ CONCLUSIONS
A new biocatalytic route has been designed and developed to
synthesize three novel sugar-PEG-based amphiphilic polymers
11ꢀ13 by copolymerization of functionalized pentofuranose
backbone with PEG-600 dimethyl ester using Novozyme-435.
Regioselectivity has been exhibited in the polymerization of
monomers 2 and 5 with PEG dimethyl ester, where PEGylation
occurs only at the primary hydroxyl groups leading to the
formation of polymers 11 and 12. All three polymers have been
explored for drug delivery application. Attachment of phenyl and
pentyl moieties to the pentofuranose backbone in the copoly-
mers 12 and 13, respectively, leads to the formation of supra-
molecular aggregates of diameters 124 and 223 nm, respectively,
in the aqueous solution, as observed by DLS. Supramolecular
aggregates of polymers 12 and 13 were capable to encapsulate
nile red molecule, as revealed by the guest enacapsulation studies
done in buffered aqueous solutions. Nile red release in case of
polymer 13 was found to be faster with a half-life time of 2.0 h
than that in the polymer 12 with a half-life time of 3.4 h at
acidic pH 5.0 (37 °C). No release was observed at physiological
pH 7.4 (37 °C), as observed by fluorescence studies of nile-red-
loaded aggregates. Further studies are in progress to achieve the
lead polymeric architectures with higher drug loading capacity
and longer lasting release profiles.
(15) Satturwar, P.; Eddine, M. N.; Ravenelle, F.; Leroux, J.-C. Eur. J.
Pharm. Biopharm. 2007, 65, 379–387.
(16) Jang, W.-D.; Nishiyama, N.; Zhang, G.-D.; Harada, A.; Jiang,
D.-L.; Kawauchi, S.; Morimoto, Y.; Kikuchi, M.; Koyama, H.; Aida, T.;
Kataoka, K. Angew. Chem., Int. Ed. 2005, 44, 419–423.
(17) Chen, W.; Meng, F.; Li, F.; Ji, S.-J.; Zhong, Z. Biomacromolecules
2009, 10, 1727–1735.
’ ASSOCIATED CONTENT
(18) Chen, W.; Meng, F.; Cheng, R.; Zhong, Z. J. Controlled Release
2010, 142, 40–46.
(19) Youssefyeh, R. D.; Verheyden, J. P. H.; Moffatt, J. G. J. Org.
Chem. 1979, 44, 1301–1309.
(20) Christensen, S. M.; Hansen, H. F.; Koch, T. Org. Process Res.
Dev. 2004, 8, 777–780.
(21) Yang, K. L.; Blackman, B.; Diederich, W.; Flaherty, P. T.;
Mossman, C. J.; Roy, S.; Ahn, Y. M.; Georg, G. I. J. Org. Chem. 2003,
68, 10030–10039.
S
Supporting Information. Experimental details of synth-
b
esis of monomers and copolymers, H NMR and 13C NMR
1
spectra of compounds 2ꢀ8 and for copolymers 11ꢀ13, DEPT-
135 NMR spectra of compounds 4ꢀ8 and for copolymers
1
1
11ꢀ13, Hꢀ H COSY spectrum of copolymer 13, and gel
permeation chromatograms of copolymers 11ꢀ13. This material
(22) Crich, D.; Li, M. J. Org. Chem. 2008, 73, 7003–7010.
(23) Yu, S.-H.; Wang, H.-Y.; Chiang, L.-W.; Pei, K. Synthesis 2007,
9, 1412–1420.
’ AUTHOR INFORMATION
(24) Prasad, A. K.; Kalra, N.; Yadav, Y.; Kumar, R.; Sharma, S. K.;
Patkar, S.; Lange, L.; Wengel, J.; Parmar, V. S. Chem. Commun.
2007, 2616–2617.
(25) Dueno, E. E.; Chu, F.; Kim, S.-I.; Jung, K. W. Tetrahedron Lett.
1999, 40, 1843–1846.
Corresponding Author
*(R.H.) Tel: +49-30-838-52633; Fax: +49-30-838-53357;
E-mail: haag@chemie.fu-berlin.de. (A.K.P.) Tel: 00-91-11-
27662486; E-mail: ashokenzyme@yahoo.com.
(26) Dhavale, D. D.; Matin, M. M. Tetrahedron 2004, 60, 4275–
4281.
(27) Gupta, S.; Pandey, M. K.; Levon, K.; Haag, R.; Watterson, A. C.;
Parmar, V. S.; Sharma, S. K. Macromol. Chem. Phys. 2010, 211, 239–244.
(28) Faber, K. Biotransformations in Organic Chemistry, 5th ed.;
Springer-Verlag: Berlin, 2004.
(29) Drauz, K.; Waldmann, H. Enzyme Catalysis in Organic Synthesis;
VCH: Weinheim, Germany, 1994; Vols. 1 and 2.
(30) Prasad, A. K.; Kalra, N.; Yadav, Y.; Singh, S. K.; Sharma, S. K.;
Patkar, S.; Lange, L.; Olsen, C. E.; Wengel, J.; Parmar, V. S. Org. Biomol.
Chem. 2007, 5, 3524–3530.
(31) Maity, J.; Shakya, G.; Singh, S. K.; Ravikumar, V. T.; Parmar,
V. S.; Prasad, A. K. J. Org. Chem. 2008, 78, 5629–5632.
(32) Singh, S. K.; Sharma, V. K.; Olsen, C. E.; Wengal, J.; Parmar,
V. S.; Prasad, A. K. J. Org. Chem. 2010, 75, 7932–7935.
(33) Kumar, R.; Chen, M.-H.; Parmar, V. S.; Samuelson, L. A.;
Kumar, J.; Nicolosi, R.; Yoganathan, S.; Watterson, A. C. J. Am. Chem.
Soc. 2004, 126, 10640–10644.
’ ACKNOWLEDGMENT
We thank the Department of Biotechnology (DBT, New
Delhi, India) and the International Bureau (IB) of the Federal
Ministry of Education and Research (BMBF, Bonn, Germany)
and the University of Delhi under the DU-DST Purse grant for
financial assistance to this work. S.B. thanks Institute for Chem-
istry and Biochemistry, Free University Berlin, Germany for
providing the opportunity and infrastructure to accomplish a part
of this work. S.B. and D.M. thank UGC, New Delhi for the award
of research fellowship.
’ REFERENCES
(1) Francesco, M. V.; Gianfranco, P. Drug Discovery Today 2005,
10, 1451–1458.
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