Synthesis of N,N-dimethyl N-ethyl Chitosan as a Carrier for Oral Delivery of Peptide Drugs

Abstract

N, N-dimethyl N-ethyl chitosan (DMEC), a quanternized derivative of chitosan was synthesized based on a modified two-step method via a 2² factorial design to optimize the preparative conditions. The degree of deacetylation of the starting chitosan was determined by FTIR and NMR methods and was 95%. In the first step of the synthesis, mono-ethyl chitosan was prepared by introducing an ethyl group onto the amine group of chitosan via a Schiff base and in the next step methyl iodide was added to produce DMEC which was water soluble in a pH range of 4-8. The DMEC polymers with different degrees of quaternization were obtained and fully characterized using FTIR and 1H-NMR spectroscopic methods. Based on 1H-NMR calculations, the degree of quaternization was 52% by optimizing the two-step process.

Keywords

chitosan quaternized chitosan drug absorption enhancer degree of quaternization

Get full access to this article

View all access options for this article.

References

Denkbas, E. and Ottenbrite, R. M. (2006). J. Bioact. Comp. Poly., 21(4) 351-367 .

Roberts, G. (1992). Chitin Chemistry, Macmillan, London .

Illum, L. (1998). Pharm. Res., 15: 1326-1331 .

Rinaudo, M. and Domard, A. (1989). Chitin and Chitosan, pp. 71-86, Elsevier Applied Sciences, London .

Thanou, M. , Florea, B. I. , Langemeyer, M. W. E. , Verhoef, J. C. , and Junginger, H. E. (2000). Pharm. Res., 17: 27-31 .

Lueßen, H. L. , Lehr, C. M. , Rentel, C. O. , Noach, A. B. J. , de Boer, A. G. , Verhoef, J. C. , and Junginger, H. E. (1994). J. Control. Rel., 29: 329-338 .

Illum, L. , Farraj, N. F. , and Davis, S. S. (1994). Pharm. Res., 11: 1186-1189 .

Artursson, P. , Lindmark, T. , Davis, S. S. , and Illum, L. (1994). Pharm. Res., 11: 1385-1391 .

Agnihotri, S. A. , Mallikarjuna, N. N. , and Aminabhavi, T. M. (2004). J. Control. Rel., 100: 5-28 .

10.

Curti, E. , de Britto, D. , and Campana, S. P. (2003). Macromol. Biosci., 3: 571-576 .

11.

Van der Merwe, S. M. , et al. , (2004). Eur. J. Pharm. Biopharm., 58: 225-235 .

12.

Thanou, M. , Verhoef, J. C. , and Junginger, H. E. (2001). Adv. Drug Del. Rev., 50: S91-S101 .

13.

Hamman, J. H. , Stander, M. , and Kotze, A. F. (2002). Int. J. Pharm., 232: 235-242 .

14.

Hamman, J. H. , Schultz, C. M. , and Kotze, A. F. (2003). Drug Dev. Ind. Pharm., 29: 161-172 .

15.

Domszy, J. G. and Roberts, G. A. F. (1985). Macromol. Chem., 186: 1671-1677 .

16.

Hiral, A. , Odani, H. , and Nakajima, A. (1991). Polym. Bull., 26: 87-94 .

17.

Wang, W. , Bo, S. , Li, S. , and Qin, W. (1991). Int. J. Biol. Macromol., 13: 281-285 .

18.

Kim, C. H. , Choi, J. W. , Chun, H. J. , and Choi, K. S. (1997). Polym. Bull., 38: 387-393 .

19.

Domard, A. , Rinaudo, M. , and Terrassin, C. (1986). Int. J. Biol. Macromol., 8: 105-107 .

20.

Barr, W. H. and Riegelman, S. (1970). J. Pharm. Sci., 59: 154-163 .

21.

Sieval, A. B. , Thanou, M. , Kotze, A. F. , Verhoef, J. C. , Brussee, J. , and Junginger, H. E. (1998). Carbohydr. Polym., 36: 157-165 .

22.

Avadi, M. R. , Erfan, M. , Sadeghi, A. M. M. , Moezi, L. , Dehpour, A. R. , Rafiee-Tehrani, M. , and Shafiee, A. (2004). J. Bioact. Compat. Polym., 19: 421-443 .

23.

Avadi, M. R. , Zohuriaan-Mehr, M. J. , Younessi, P. , Amini, M. , Rafiee-Tehrani, M. , and Shafiee, A. (2003). J. Bioact. Comp. Polm., 18: 469-469 .

24.

Kim, C. H. , Jang, W. C. , Heung, J. C. , and Kyu, S. C. (1996). Polym. Bull., 38: 387-393 .

25.

Yao, K. D. , Yin, Y. J. , Xu, M. X. , and Wang, Y. F. (1995). Polym. Int., 38: 77-80 .

26.

Desbrieres, J. , Martinez, C. , and Rinaudo, M. (1996). Int. J. Biol. Macro-mol., 19: 21-28 .