Poly(N-isopropylacrylamide), poly(methacrylic acid) and their copolymers for oral colon-specific drug delivery

Abstract

A series of cross-linked gels of Poly(N-isopropylacrylamide) [P(NIPAAm)] and Poly(methacr-ylic acid)[P(MAA)] homopolymers and P(NIPAAm-co-MAA) random copolymers were synthesized based on NIPAAm and MAA using 4,4-Bis-(methacryloylamino) azobenzene (BMAAB) as a cross-linker. The swelling behavior of these hydrogels in different pH buffer solutions was studied. The influential factors of the gels including composition of NIPAAm and MAA, pH and temperature upon swelling behavior were investigated. The obtained gels not only hold pH and thermometrical sensitivity, but also take on enzymatic sensitivity due to the cross-linker could be degraded by enzymes of colon. Swelling equilibrium degree of copolymers was very low in acidic medium, which could avoid drug releasing due to biggish swelling of carrier in stomach. Hydrogels would partly swell owing to higher pH value in small intestine. When arrived in colon, hydrogels completely swelled, meanwhile, azoenzymes located would degrade azo-bonds of polymeric network and then drug released in colon.

Keywords

pH sensitivity / thermometrical sensitivity / colon-specific

References

[1] Maroni A., Curto M. D. D., Serratoni M., . Feasibility, Stability and Release Performance of a Time-dependent Insulin Delivery System Intended for Oral Colon Release[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2009, 72: 246-251.

[2] Malik D. K., Baboota S., Ahuja A., . Recent Advances in Protein and Peptide Drug Delivery Systems[J]. Curr. Drug Deliv., 2007, 4: 141-151.

[3] Lin Y., Chen Q., Luo H. Preparation and Characterization of N-(2-carboxybenzyl)chitosan as a Potential pH-sensitive Hydrogel for Drug Delivery[J]. Carbohydrate Research, 2007, 342: 87-95.

[4] Yin Y., Yang Y., Xu H. Swelling Behavior of Hydrogels for Colon-Site Drug Delivery[J]. Journal of Applied Polymer Science, 2002, 83: 2835-2842.

[5] Mahkam M. New pH-sensitive Glycolpolymers for Colon-specific Drug Delivery[J]. Drug Delivery, 2007, 14: 147-153.

[6] Gazzaniga A., Maroni A., Sangalli M.E., . Time-controlled Oral Delivery Systems for Colon Targeting[J]. Expert Opin. Drug Deliv., 2006, 3: 583-597.

[7] Yin Y., Yang Y., Xu H. Hydrogels for Colon-Specific Drug Delivery: Swelling Kinetics and Mechanism of Degradation in vitro[J]. Journal of Polymer Science Part B: Polymer Physics, 2001, 39(24): 3128-3137.

[8] Musial W., Kubis A. Biodegradable polymers for Colon-specific Drug Delivery[J]. Polim. Med., 2005, 35: 51-61.

[9] Jain A., Gupta Y., Jain S.K. Azo Chemistry and Its Potential for Colonic Delivery[J]. Critical Reviews in Therapeutic Drug Carrier Systems, 2006, 23: 349-400.

[10] Sinha V.R., Kumria R. Colonic Drug Delivery: Prodrug Approach[J]. Pharmaceutical Research, 2001, 18: 557-564.

[11] Yin Y., Yang Y., Xu H. Swelling Kinetics of Hydrogels for Colon-site Drug Delivery[J]. Acta Polymerica Sinica, 2001, 5: 650-655.

[12] Díez-Peńa E., Quijada-Garrido I., Barrales-Rienda J. M. Analysis of the Swelling Dynamics of Cross-Linked P(N-iPAAm-co-MAA) Copolymers and Their Homopolymers under Acidic Medium. A Kinetics Interpretation of the Overshooting Effect[J]. Macromolecules, 2003, 36: 2475-2483.

[13] Díez-Peńa E., Quijada-Garrido I., Barrales-Rienda J. M. Influence of the Hydrogen Bonding on the Swelling Behavior of P[(N-iPAAm)-co-(MAA)] Copolymers. A Case of Autocatalytic Swelling Kinetics[J]. Macromolecules, 2002, 35: 8882-8888.

[14] Yin Y., Dong H., Ji X. Study on the Swelling Dynamics of Carboxy Methyl Cellulose-graftpoly(acrylic acid) Hydrogels and the Overshooting Effect[J]. Acta Chimica Sinica, 2007, 65(3): 271-278.

[15] Koussathana M., Lianos P., Staikos G. Investigation of Hydrophobic Interactions in Dilute Aqueous Solutions of Hydrogen-Bonding Interpolymer Complexes by Steady-State and Time-Resolved Fluorescence Measurements[J]. Macromolecules, 1997, 30: 7798-7802.

[16] Nonaka T., Yoda T., Kurihara S. Swelling Behavior of Thermo-sensitive Polyvinyl Alcoholgraft-N-isopropylacrylamide Copolymer Membranes Containing Carboxyl Groups and Properties of Their Polymer Solutions[J]. Journal of Polymer Science Part A: Polymer Chemistry, 1998, 36(17): 3097-3106.