Colon-Specific Delivery of IgG from Highly Swellable Dextran Hydrogels: In-Vitro Study

Yıl 2007, Cilt: 35 Sayı: 3, 163 - 171, 01.08.2007

Dilek İmren Menemşe Gümüşderelioğlu Ali Güner

Öz

Colonic drug delivery has gained increased importance for the delivery of peptide and protein drugs. In this study, thestrategy is to investigate release of high molecular weight MW protein drugs from dextran-based hydrogels.The hydrogels were synthesized in the presence of crosslinking agents, N,N’-methylenebisacrylamide MBAm andepichlorohydrin ECH . While dextran-MBAm hydrogels are having average equilibrium swelling ratios between 12.0 at pH 2 and 14.0 at pH 7 , dextran-ECH hydrogels have values between 9.0 at pH 2 and 12.5 at pH 7 . Themodel high molecular weight protein, immunoglobulin G IgG , was loaded into the 50% by weight crosslinkercontaining dextran hydrogels by two ways, i.e. during the crosslinking reaction or by soaking method. The loadingcapacity was varied between 3.0 and 4.0 mg per g of dry gel by depending upon the loading procedure. In-vitrorelease experiments were performed in the simulated gastrointestinal system in the presence and absence ofdextranase. The diffusion exponents were calculated by means of the semi-empirical power law equation indicatedthat IgG was mainly released by non-Fickian diffusion. The release of IgG from both hydrogels was substantiallyhigher than that of similar systems especially in the presence of dextranase, which was attributed to the highswellability of the dextran hydrogels synthesized here

Anahtar Kelimeler

Dextran, protein delivery, hydrogels, IgG, colon-specific delivery

Kaynakça

• R.J.H. Stenekes, A.E. Loebis, C.M. Fernandes, D.J.A. Crommelin and W.E. Hennink, Pharm. Res., 17 (2000) 690. 11. L. Howgaard and H. Brİndsted, J. Control. Release. 36 (1995) 159.
• A. Güner, Ö. Akman and Z.M.O. Rzaev, React. Funct. Polym., 47 (2001) 55.
• D. İmren, M. Gümüşderelioğlu and A. Güner, Biochem. Eng. J., (2007) (submitted).
• A.K. Doğan, M. Gümüşderelioğlu and E. Aksöz, J. Biomed. Mat. Res. Part B:Appl Biomat., 74B 1 (2005) 504.
• D. İmren, M. Gümüşderelioğlu and A. Güner, J. Appl. Polym. Sci., 102 (2006) 4213.
• H. Schoot, J. Macromol. Sci-Phys., 31B (1992) 1.
• P.J. Flory and R. Rehner, J. Chem. Phys., 11 (1943) 521.
• N.A. Peppas and E.W. Merril, J. Polym. Sci Polym. Chem., 14 (1976) 459. 19.E.W. Merril, K.A. Dennison and C. Sung, Biomaterials., 14 (1993) 1117.
• V. Carelli, G. Di Colo, E. Nannipieri and M.F. Serafini, Int. J. Pharm., 55 (1989) 199.
• L. Yang, C. Chu and J.A. Fix, Int. J. Pharm., 235 (2002) 1.
• H.C. Chiu, A.T. Wu and Y.F. Lin, Polymer, 42 (2001) 1471.
• W.E. Hennink, H. Talsma, J.C:H. Borchert, S.C. de Smedt and J. Demeester, J. Control. Release., 39 (1996) 47.
• P.L. Ritger and N.A. Peppas, J. Control. Release, 5 (1987) 37.