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Abstract

The α-amylase induced enzymatic degradation of terpolymeric beads, composed of calcium alginate, starch and poly(ethylene) glycol, were studied for gastrointestinal drug delivery. The beads demonstrated faster degradation with increased enzyme activity in the range 0.64 to 2.24IU/mL. A linear relationship of the degradation rates and corresponding enzyme concentration indicate that degradation is governed by Michaelis-Menten kinetics. The degradation rate was enhanced with increases in starch content in the beads. The smaller value of KM (3.15 × 10⁻⁵ mol⁻¹ dm⁻³) indicated higher enzyme-substrate affinity. The beads crosslinked with barium ions demonstrated slower degradation due to a higher degree of crosslinking in the beads. With increases in initial water content, the degradation was found to increase. In order to incorporate in vivo GI conditions, the degradation was also studied using a flow through diffusion cell (FTDC). The hydrogel beads exhibited slower degradation by FTDC compared to traditional in vitro methods and the degradation was dependent on the nature of the filler particles used in the diffusion cell.

Keywords

enzyme degradation polymeric beads gastrointestinal drug delivery amylase sodium alginate beads flow through diffusion cell FTDC

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References

Reddy, S.M. , Sinha, V.R. and Reddy, D.S. (1999). Oral Colon Specific Drug Delivery Systems for Pharmacotherapy of Peptide and Nonpeptide Drugs , Drugs of Today, 35: 537–580 .

Mehvar, R. (2000). Dextrans for Targeted and Sustained Delivery of Therapeutic and Imaging Agents , J. Cont. Release, 69: 47–47 .

Kakoulidaes, E.P. , Smart, J.D. and Tsibouklis, J. (1998). Azo Crosslinked Poly(acrylic acid) for Colonic Delivery and Adhesion Specificity: In Vitro Degradation and Preliminarily Ex Vivo Bioadhesion Studies , J. Cont. Release, 54: 95–109 .

Cadee, J.A. , Groot de, C.J. , Jiskoot, W. , den Otter, W. and Hennink, W.E. (2002). Release of Recombinant Human Interleukin-2 from Dextran-based Hydrogels , J. Cont. Release, 78(1–3): 1-1 .

Ruiwen, Shi , and Helen Burt, M. (2004). Amphiphilic Dextran Graftpoly(caprolactone) Films for the Controlled Release of Paclitaxel . Int. J. Pharmac., 271: 167–179 .

De Jong, S.J. , Van Eerdenbrugh, B. , Van Nostrum, C.F. , Kettenes,Van den , Bosch, J.J. and Hennink, W.E. (2001). Physically Crosslinked Dextran Hydrogels by Stereocomplex Formation of Lactic Acid Oligomers: Degradation and Protein Release Behavior , J. Cont. Release, 71: 261–275 .

Kabir, I. , Vagen, B. , Batuom, M. and Rubinstein, A. (2003). Phosphate Cross-linked Guar for Colon-specific Drug Delivery , J. Cont. Release, 63(1–2): 129-129 .

Sardar, M. , Roy, I. and Gupta, M.N , (2003). A Smart Bioconjugate of Alginate and Pectinase with Unusual Biological Activity Toward Chitosan , Biotechnol. Prog., 19: 1654–1658 .

Stubbe, B. , Maris, G. , Mooter, Van den , De Smedt, S.C. , Demeester, J. and Guy, Van Den. (2001). The In Vitro Evaluation of Azo Containing Polysaccharides Gels for Colon-delivery , J. Cont. Release, 75: 103–103 .

10.

Tuovinen, L. , Peitonen, S. , Lilkola, M. , Hotakainea, M. , Lahtela, M. , Paso, A. and Jarvinen, K. (2004). Drug Release from Starch-Acetate Microparticles and Films with and without Incorporated α-amylase , Biomaterials, 25(18): 4355–4362 .

11.

Hovgaard, L. and Brondated, H. (1995). Dextran Hydrogels for Colon-specific Drug-delivery , J. Control. Release, 34: 159–159 .

12.

Fronssen, O. , Vandervennel, L. , Raders, P. and Hennink, W.E. (2000). Chemically Degrading Dextran Hydrogels: Controlled Release of a Model Protein from Cylinders and Microspheres , J. Cont. Release, 60: 211–211 .

13.

Fathima, N.N. , Madhan, B. , Rao, J.R. , Nair, B.U. and Ramasami, T. (2004). Interaction of Aldehydes with Collagen: Effect on Thermal, Enzymatic and Conformational Stability , Int. J. Biolog. Macromolecules, 34(4): 241–247 .

14.

Bronsted, H. , Hovagaard, L. and Simonsen, L. (1995). Dextran Hydrogels for Colon-specific Drug Delivery. In Comparative Release Study of Hydrocortisone and Prednisolone Sodium Phosphate , STP Pharm. Sci., 5: 65–65 .

15.

Bajpai, S.K. and Sharma, S. (2004). Investigation of Swelling/Degradation Behaviour of Alginate Beads Cross-linked with Ca2+ and Ba2+ Ions , React. and Funct., 59: 129–140 .

16.

Azevedo, H.S. , Gama, F.M. and Reis, R.L. (2003). In Vitro Assessment of the Enzymatic Degradation of Several Starch Based Biomaterials , Biomacromolecules, 4: 1703–1703 .

17.

Miller, G.L. (1959). Use of Dinitrosalicylic Acid Reagent for Determination of the Amount of Reducing Sugar , Anal. Chem., 31: 420–420 .

18.

Hamidi, G. , Ponchal, G. and Duchene, D. (1998). An Original Method for Studying In Vitro the Enzymatic Degradation of Cross-linked Starch Microspheres , J. Cont. Release, 55: 193–201 .

19.

Araki, Y. , Anodh, A. , Fujiyama, Y. and Itoh, A. (2002), Int. J. Molecular Medicine, 9: 627–627 .

20.

Plummer, D.T. (1997). An Introduction to Practical Biochemistry, 3rd edn, Tata McGraw Hill, 226–231.

21.

Fronssen, O. , Vos, O.P. and Hennink, W.E. (1997). Delayed Release of a Model Protein from Enzymatically Degrading Dextran Hydrogels , J. Cont. Release, 44: 237–245 .

22.

Aslani, P. and Kennedy, R.A. (1996). Studies on Diffusion in Alginate Gels. I. Effect of Crosslinking with Calcium or Zinc Ions on Diffusion of Acetaminophen , J. Cont. Release, 42: 75–82 .

23.

Hennink, W.E. , Talsma, H. , Barchert, J.C.H. , De Smedt, S.C. and Demeester, J. (1996). Controlled Release of Protein from Dextran Hydrogels , J. Cont. Release, 39: 47–55 .

24.

Kenyon, C.J. , Hooper, G. , Tierney, D. , Butler, J. , Devance, J. and Wilding, I.R. (1995). The Effect of Food on the Gastrointestinal Transit Time and Systematic Absorption of Naproxen from a Novel Sustained Release Formulation , J. Cont. Release, 34: 31–36 .

25.

Ahmed, I.S. (2005). Effect of Simulated Gastrointestinal Conditions on Drug Release from Pectin/Ethyl Cellulose as Film Coating for Drug Delivery to the Colon , Drug Dev. and Ind. Pharm., 31(4–5): 465–470 .

A Novel Approach to Study Enzymatic Degradation of Ter-polymeric Beads for Gastrointestinal Drug Delivery: Synthesis and Characterization

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