Characteristics of Natural Polysaccharides for Colon Drug Targeting
DOI:
https://doi.org/10.37285/ijpsn.2019.12.1.2Abstract
Targeting drugs directly to the colon is advantageous in the topical treatment of colonic diseases such as ulcerative colitis and Crohn’s disease and has shown potential in gaining the oral delivery of peptides and other labile drugs. A colonic drug delivery system is required to protect a drug during its transit through the upper gastro-intestinal (G.I.T.) tract and allow its release in the colon. Several methods of colonic targeting have been proposed. These include taking advantage of the apparent consistency of small intestinal transit times, the utilization of pH changes within the G.I. tract and the exploitation of bacterial enzymes localized in the colonic region of the G.I. tract. Among the different approaches to achieve targeted drug release to the colon, the use of polymers especially biodegradable by colonic bacteria holds great promise. Polysaccharides are bacterial enzymes that are available in sufficient quantity to be exploited in colon targeting of drugs. Based on this approach, various polysaccharides have been investigated for colon-specific drug release. These polysaccharides include pectin, guar gum, amylose, inulin, dextran, chitosan, and chondroitin sulfate. This family of natural polymers has an appeal to drug delivery as it is comprised of polymers with a large number of derivatizable groups, a wide range of molecular weights, varying chemical compositions, and, for the most part, low toxicity and biodegradability yet high stability. The most favorable property of these materials is their approval as pharmaceutical excipients. Polysaccharides are bacterial enzymes that are available in sufficient quantity to degrade these natural polysaccharides.
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Keywords:
Colonic drug delivery system, Biodegradable, Natural polysaccharides
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Published
2019-01-31
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1.
Kumar A, Pandey K A. Characteristics of Natural Polysaccharides for Colon Drug Targeting. Scopus Indexed [Internet]. 2019 Jan. 31 [cited 2024 Nov. 19];12(1):4362-70. Available from: https://ijpsnonline.com/index.php/ijpsn/article/view/275
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Review Articles
References
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Allcock HR and Ambrosio AMA (1996). Synthesis and characteriza-tion of pH-sensitive poly (organophosphazene) hydrogels, Biomaterials 17: 2295-2302.
Amrutkar, JR. and Gattani, SG (2009). Chitosan–Chondroitin Sulfate Based Matrix Tablets for Colon Specific Delivery of Indomethacin. AAPS Pharm Sci Tech., 10: 670-677.
Anal, AK.; Bhopatkar, D.; Tokura, S.; Tamura, H. and Stevens, WF (2003). Chitosan–alginate multilayer beads for gastric passage and controlled intestinal release of protein. Drug Dev. Ind. Pharm., 29: 713-724.
Anil, K A. and Willem, FS (2005). Chitosan–alginate multilayer beads for controlled release of ampicillin. International Journal of Pharmaceutics, 290: 45-54.
Aysu, Yurdasiper. and Ferhan, Sevgi (2010). An overview of modified release chitosan, alginate and eudragit RS microparticles. J. Chem. Pharm. Res., 2(3): 704-721.
Bagyalakshmi, J.; Arun Raj, R.; and Ravi, TK (2011). Fomulation, physical charecterisation and in-vitro release studies of prednisolone alginate beads for colon targeting by ionotropic gelation. Pharmacie Globale (IJCP) 3: 4-12.
Cavalcanti, OA.; Silva, CC.; Pineda, EG. and Hechenleitner, AW (2005). Synthesis and characterization of phosphated crosslinked chondroitin sulfate: Potencial ingredient for specific drug delivery. Acta Farmaceutica Bonaerense 24: 234-238.
Chambin, OG.; Dupuis, G.; Champion, D.; Voilley, A. and Pourcelot, Y (2006). Colon-specific drug delivery: Influence of solution reticulation properties upon pectin beads performance. International Journal of Pharmaceutics 321: 86-93.
Chourasia, MK. and Jain, SK (2003). Pharmaceutical approaches to colon targeted drug delivery systems. J. Pharm Pharm Sci 6: 33-66.
Cummings, JH.; Milojevic, S.; Harding, M.; Coward, WA.; Gibson, GR. and Botham, RL (1996). In vivo studies of amylose and ethylcellulose coated [13C]glucose microspheres as a model for drug delivery to the colon. J Control Release 40: 123-131.
Daris, M.; Williams, R. and Chakraborty, J (1997). Prednisone or prednisolone for the treatment of chronic active hepatitis? A comparison of plasma availability. Brit. J. Clin. Pharmaco, 5(6): 501-505.
Dodane V and Vilivalam, VD (1998). Pharmaceutical applications of chitosan. PSTT 1: 246-/253.
George M and Abraham TE (2007). pH sensitive alginate-guar gum hydrogel for the controlled delivery of protein drugs. International Journal of Pharmaceutics, 335: 123-129.
González-Rodríguez ML, Holgado, MA.; Sánchez-Lafuente, C.; Rabasco, AM and Fini A (2002). Alginate/chitosan particulate systems for sodium diclofenac release. Int. J. Pharm 232(1–2): 225-234.
Hovgaard, L. and Brondsted, H (1995). Dextran hydrogels for colon-specific drug delivery. J Control Release 36: 159-166.
Jain, S. and Jain, NK (2006). Polymers in Pharmaceutical Sciences. Pharmaceutical Product Development. 1st ed.; CBS Publisher and Distributor: New Delhi, 218-26.
Kajale, AD.; Kamble, RS.; Giradkar, KP.; Bakde, BV.; Channawar, MA. and Dr. Chandewar, AV (2010). Colon targeted drug delivery using natural polymers, IJPRD 2: 003.
Ketan, GA.; Vaibhav SW. and Bhagwat BC (2012). Cross-linked chitosan diclofenac sodium beads for sustained release systems. Der Pharmacia Lettre 4 (1): 110-127.
Khare, AR. and Peppas, NA (1995). Swelling/deswelling of ionic copolymer gels, Biomaterials, 18, 559– 567.
Kinage, Krishna.; Nandgude, T.; Bhaise, K. and Deshmukh, P (2009). Studies On Development of oral Colon Targeted Drug Delivery System of Locust Been and Xanthangum, International Journal of Green Pharmacy, 6, 33-36.
Kulick, WM.; Nottelmann, H.; Aggour, YA. and Elsabee, MZ (1989). Preparation characterization and rheological behavior of water-swellable Polymers, Polymer Mater. Sci. Eng., 61, 393–397.
Lenaerts, V.; Dumoulin, Y. and Mateescu, MA (1991). Controlled Release of Theophylline from Cross-linked Amylose Tablets. J Control Release., 15, 39-46.
Liu, L.; Fishman, ML.; Kost, J. and Hicks, KB (2003). Pectin-based systems for colon specific drug delivery via oral route. Biomaterials., 24, 3333-3343.
Lorenzo-Lamosa, ML., Remunan-Lopez, C., Vila-Jato, JL. and Alonso, MJ (1998). Design of microencapsulated chitosan microspheres for colonic drug delivery. J. Control. Release, 52, 109-118.
M. Prabaharan (2011). Prospective of guar gum and its derivatives as controlled drug delivery systems. International Journal of Biological Macromolecules, 49, 117-124.
Majeti, NV. and Ravi, K (2000). A review of chitin and chitosan applications. Reactive & Functional Polymers. J. Pharm. Sci., 46, 1-27.
McLeod, AD.; Friend, DR. and Tozer, TN (2006). Glucocorticoid-dextran conjugates as potential prodrugs for colon-specific delivery: Hydrolysis in rat gastrointestinal tract contents. J Pharm Sci., 83, 1284-1288.
Milojevic, S.; Newton, JM.; Cummings, JH.; Gibson, GR.; Botham, RL. and Ring, SC (1996). Amylose as a coating for drug delivery to the colon: Preparation and in vitro evaluation using 5-aminosalicylic acid pellets. J. Control Release., 38, 75-84.
Milojevic, S.; Newton, JM.; Cummings, JH.; Gibson, GR.; Botham, RL. and Ring, SC (1996). Amylose as a coating for drug delivery to the colon: Preparation and in vitro evaluation using 5-aminosalicylic acid pellets. J. Control Release., 38, 85-94.
Mohammad Reza, A.; Amir Hossein, G.; AssaI Mir Mohammad, S.; Erfan, M.; Azim A.; Hamid, R. M. and Mortaza, RT (2004). Preparation and Characterization of Theophylline-Chitosan Beads as an Approach to Colon Delivery. IJPR, 2, 73-80.
Norihito, S.; Toshihito, T.; Masumi, U.; Masaaki, M.; Yutaka, H. and Yasuhiko, N (2002). Chitosan dispersed system for colon-specific drug delivery. International Journal of Pharmaceutics, 245, 45-54.
Østberg, T.; and Graffner, C (1994). Calcium alginate matrices for oral multiple unit administration: III. Influence of calcium concentration, amount of drug added and alginate characteristics on drug release. Int. J. Pharm., 111(3), 271-282.
Østberg, T.; Lund, E. M.; and Graffner. C (1994). Calcium alginate matrices for oral multiple unit administration: IV. Release characteristics in different media. Int. J. Pharm., 112(3), 241-248.
P. Smrdel (2006). Characterization of Calcium Alginate Beads Containing Structurally Similar Drugs. Drug Development and Industrial Pharmacy, 32, 623–633.
Patel Parul, K.; Satwara Rohan, S. and Pandya, SS (2012). Bacteria aided biopolymers as carriers for colon specific drug delivery system: a review. Int. J. Pharm Tech Res. 4, 1192-1214.
Patel, HK.; Nagle, A. and Murthy, RSR (2008). Characterization of calcium alginate beads of 5 flurouracil for colon delivery. Asian j. pharm, 2, 241-245.
Raja, MD.; Narra, K.; Dhanalekshmi, UM.; Senthil, KC.; Rangaraj, G.; Reddy, NP.; Uma TS.; Sehgal, PK (2011). Formulation and in vitro evaluation of floating alginate gel beads for site specific delivery of acyclovir, 2(1), 31-42.
Rama Prasad YV.; Krishnaiah YSR. and Satyanarayana. S (1998). In vitro evaluation of guar gum as a carrier for colon-specific drug delivery. Journal of Controlled Release, 51, 281-287.
Ravindra, R.; Krovvidi, KR. and Khan, AA (1998). Solubility parameter of chitin and chitosan. Carbohydrate Polymers, 36, 121-127.
Rubinstein, A.; Nakar, D. and Sintov (1992). A Colonic drug delivery: Enhanced release of indomethacin from cross linked chondroitin matrix in rat cecal content. Pharm Res., 9, 276-8.
Rubinstein, A.; Nakar, D. and Sintov (1992). A. Chondroitin sulfate: A potential biodegradable carrier for colon-specific drug delivery. Int J Pharm., 84, 141-50.
Sangeetha, S.; Sakthisaravanan, V.; Komala, M.; Harish, G. and Siva, kV (2004). Design and evaluation of gastroretentive beads of theophylline by ionotropic gelation. Int J Pharmacy and Pharm Sci, 2(3), 99-101.
Shu, X Z. and Zhu, KJ (2000). A novel approach to prepare tripolyphosphate: chitosan complex beads for controlled release drug delivery. International Journal of Pharmaceutics. 2000, 201. 51-58.
Shu, XZ. and Zhu, KJ (2002). Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure. International Journal of Pharmaceutics, 233, 217-225.
Sinha, VR.; Kumria, R (2001). Polysaccharides in colon-specific drug delivery. Int. J. Pharm., 224, 19-38.
Sinha, VR.; Mittal, BR.; Bhutani, KK. and Kumria, R (2004). Colonic drug delivery of 5-fluorouracil: an in vitro evaluation. International Journal of Pharmaceutics, 269, 101-108.
Thakur, S.; Ghanshyam, S. and Chauhan, Ahn. JH (2009). Synthesis of acryloyl guar gum and its hydrogel materials for use in the slow release of L-DOPA and L-tyrosine. Carbohydrate Polymers, 76, 513-520.
Tønnesen, H. H.; and Karlsen, J (2002). Alginate in drug delivery systems. Drug. Dev. Ind. Pharm., 28(6), 621-630.
Tozaki, H.; Komoike, J.; Tada, C.; Maruyama, T.; Terabe, A.; Suzuki, T.; Yamamoto, A.; Muranishi, S (1997). Chitosan capsules for colon-specific drug delivery: improvement of insulin absorption from the rat colon. J. Pharm. Sci., 86, 1016-1021.
Vandamme, Th. F.; Lenourry, A.; Charrueau, C.; and Chaumeil, C (2000). The use of polysaccharides to target drugs to the colon. Carbohydrate Polymers, 48, 219-231.
Vervoort, L.; Mooter, GV.; Augustijns, P. and Kinget, R (1998). Inulin hydrogels. I. Dynamic and equilibrium swelling properties. Int J Pharm., 172, 127-135.
Vervoort, L.; Rombaut, P.; Mooter, GV.; Augustijns, P. and Kinget, R (1998). Inulin hydrogels. II. In vitro degradation study. Int J Pharm., 172, 137-145.
Vyas, SP.; Khar, RK (2002). Systems for colon specific delivery. Controlled drug delivery: Concept and advantages. 1st ed.; Vallabh Prakashan: Delhi, 2002, 218–56.
Wilson, CG,.; Mukherji, G. and Sha, HK (2008). Modified-release Drug Delivery Technology. Biopolymers and Colonic Delivery, 2, 295-309.
Xiaoxia, Li.; Hongguo, Xie.; Junzhang, Lin.; Weiyang Xiea.; and Xiaojun, M (2009). Characterization and biodegradation of chitosan–alginate polyelectrolyte complexes. Polymer Degradation and Stability. 94, 1-6.
Allcock HR and Ambrosio AMA (1996). Synthesis and characteriza-tion of pH-sensitive poly (organophosphazene) hydrogels, Biomaterials 17: 2295-2302.
Amrutkar, JR. and Gattani, SG (2009). Chitosan–Chondroitin Sulfate Based Matrix Tablets for Colon Specific Delivery of Indomethacin. AAPS Pharm Sci Tech., 10: 670-677.
Anal, AK.; Bhopatkar, D.; Tokura, S.; Tamura, H. and Stevens, WF (2003). Chitosan–alginate multilayer beads for gastric passage and controlled intestinal release of protein. Drug Dev. Ind. Pharm., 29: 713-724.
Anil, K A. and Willem, FS (2005). Chitosan–alginate multilayer beads for controlled release of ampicillin. International Journal of Pharmaceutics, 290: 45-54.
Aysu, Yurdasiper. and Ferhan, Sevgi (2010). An overview of modified release chitosan, alginate and eudragit RS microparticles. J. Chem. Pharm. Res., 2(3): 704-721.
Bagyalakshmi, J.; Arun Raj, R.; and Ravi, TK (2011). Fomulation, physical charecterisation and in-vitro release studies of prednisolone alginate beads for colon targeting by ionotropic gelation. Pharmacie Globale (IJCP) 3: 4-12.
Cavalcanti, OA.; Silva, CC.; Pineda, EG. and Hechenleitner, AW (2005). Synthesis and characterization of phosphated crosslinked chondroitin sulfate: Potencial ingredient for specific drug delivery. Acta Farmaceutica Bonaerense 24: 234-238.
Chambin, OG.; Dupuis, G.; Champion, D.; Voilley, A. and Pourcelot, Y (2006). Colon-specific drug delivery: Influence of solution reticulation properties upon pectin beads performance. International Journal of Pharmaceutics 321: 86-93.
Chourasia, MK. and Jain, SK (2003). Pharmaceutical approaches to colon targeted drug delivery systems. J. Pharm Pharm Sci 6: 33-66.
Cummings, JH.; Milojevic, S.; Harding, M.; Coward, WA.; Gibson, GR. and Botham, RL (1996). In vivo studies of amylose and ethylcellulose coated [13C]glucose microspheres as a model for drug delivery to the colon. J Control Release 40: 123-131.
Daris, M.; Williams, R. and Chakraborty, J (1997). Prednisone or prednisolone for the treatment of chronic active hepatitis? A comparison of plasma availability. Brit. J. Clin. Pharmaco, 5(6): 501-505.
Dodane V and Vilivalam, VD (1998). Pharmaceutical applications of chitosan. PSTT 1: 246-/253.
George M and Abraham TE (2007). pH sensitive alginate-guar gum hydrogel for the controlled delivery of protein drugs. International Journal of Pharmaceutics, 335: 123-129.
González-Rodríguez ML, Holgado, MA.; Sánchez-Lafuente, C.; Rabasco, AM and Fini A (2002). Alginate/chitosan particulate systems for sodium diclofenac release. Int. J. Pharm 232(1–2): 225-234.
Hovgaard, L. and Brondsted, H (1995). Dextran hydrogels for colon-specific drug delivery. J Control Release 36: 159-166.
Jain, S. and Jain, NK (2006). Polymers in Pharmaceutical Sciences. Pharmaceutical Product Development. 1st ed.; CBS Publisher and Distributor: New Delhi, 218-26.
Kajale, AD.; Kamble, RS.; Giradkar, KP.; Bakde, BV.; Channawar, MA. and Dr. Chandewar, AV (2010). Colon targeted drug delivery using natural polymers, IJPRD 2: 003.
Ketan, GA.; Vaibhav SW. and Bhagwat BC (2012). Cross-linked chitosan diclofenac sodium beads for sustained release systems. Der Pharmacia Lettre 4 (1): 110-127.
Khare, AR. and Peppas, NA (1995). Swelling/deswelling of ionic copolymer gels, Biomaterials, 18, 559– 567.
Kinage, Krishna.; Nandgude, T.; Bhaise, K. and Deshmukh, P (2009). Studies On Development of oral Colon Targeted Drug Delivery System of Locust Been and Xanthangum, International Journal of Green Pharmacy, 6, 33-36.
Kulick, WM.; Nottelmann, H.; Aggour, YA. and Elsabee, MZ (1989). Preparation characterization and rheological behavior of water-swellable Polymers, Polymer Mater. Sci. Eng., 61, 393–397.
Lenaerts, V.; Dumoulin, Y. and Mateescu, MA (1991). Controlled Release of Theophylline from Cross-linked Amylose Tablets. J Control Release., 15, 39-46.
Liu, L.; Fishman, ML.; Kost, J. and Hicks, KB (2003). Pectin-based systems for colon specific drug delivery via oral route. Biomaterials., 24, 3333-3343.
Lorenzo-Lamosa, ML., Remunan-Lopez, C., Vila-Jato, JL. and Alonso, MJ (1998). Design of microencapsulated chitosan microspheres for colonic drug delivery. J. Control. Release, 52, 109-118.
M. Prabaharan (2011). Prospective of guar gum and its derivatives as controlled drug delivery systems. International Journal of Biological Macromolecules, 49, 117-124.
Majeti, NV. and Ravi, K (2000). A review of chitin and chitosan applications. Reactive & Functional Polymers. J. Pharm. Sci., 46, 1-27.
McLeod, AD.; Friend, DR. and Tozer, TN (2006). Glucocorticoid-dextran conjugates as potential prodrugs for colon-specific delivery: Hydrolysis in rat gastrointestinal tract contents. J Pharm Sci., 83, 1284-1288.
Milojevic, S.; Newton, JM.; Cummings, JH.; Gibson, GR.; Botham, RL. and Ring, SC (1996). Amylose as a coating for drug delivery to the colon: Preparation and in vitro evaluation using 5-aminosalicylic acid pellets. J. Control Release., 38, 75-84.
Milojevic, S.; Newton, JM.; Cummings, JH.; Gibson, GR.; Botham, RL. and Ring, SC (1996). Amylose as a coating for drug delivery to the colon: Preparation and in vitro evaluation using 5-aminosalicylic acid pellets. J. Control Release., 38, 85-94.
Mohammad Reza, A.; Amir Hossein, G.; AssaI Mir Mohammad, S.; Erfan, M.; Azim A.; Hamid, R. M. and Mortaza, RT (2004). Preparation and Characterization of Theophylline-Chitosan Beads as an Approach to Colon Delivery. IJPR, 2, 73-80.
Norihito, S.; Toshihito, T.; Masumi, U.; Masaaki, M.; Yutaka, H. and Yasuhiko, N (2002). Chitosan dispersed system for colon-specific drug delivery. International Journal of Pharmaceutics, 245, 45-54.
Østberg, T.; and Graffner, C (1994). Calcium alginate matrices for oral multiple unit administration: III. Influence of calcium concentration, amount of drug added and alginate characteristics on drug release. Int. J. Pharm., 111(3), 271-282.
Østberg, T.; Lund, E. M.; and Graffner. C (1994). Calcium alginate matrices for oral multiple unit administration: IV. Release characteristics in different media. Int. J. Pharm., 112(3), 241-248.
P. Smrdel (2006). Characterization of Calcium Alginate Beads Containing Structurally Similar Drugs. Drug Development and Industrial Pharmacy, 32, 623–633.
Patel Parul, K.; Satwara Rohan, S. and Pandya, SS (2012). Bacteria aided biopolymers as carriers for colon specific drug delivery system: a review. Int. J. Pharm Tech Res. 4, 1192-1214.
Patel, HK.; Nagle, A. and Murthy, RSR (2008). Characterization of calcium alginate beads of 5 flurouracil for colon delivery. Asian j. pharm, 2, 241-245.
Raja, MD.; Narra, K.; Dhanalekshmi, UM.; Senthil, KC.; Rangaraj, G.; Reddy, NP.; Uma TS.; Sehgal, PK (2011). Formulation and in vitro evaluation of floating alginate gel beads for site specific delivery of acyclovir, 2(1), 31-42.
Rama Prasad YV.; Krishnaiah YSR. and Satyanarayana. S (1998). In vitro evaluation of guar gum as a carrier for colon-specific drug delivery. Journal of Controlled Release, 51, 281-287.
Ravindra, R.; Krovvidi, KR. and Khan, AA (1998). Solubility parameter of chitin and chitosan. Carbohydrate Polymers, 36, 121-127.
Rubinstein, A.; Nakar, D. and Sintov (1992). A Colonic drug delivery: Enhanced release of indomethacin from cross linked chondroitin matrix in rat cecal content. Pharm Res., 9, 276-8.
Rubinstein, A.; Nakar, D. and Sintov (1992). A. Chondroitin sulfate: A potential biodegradable carrier for colon-specific drug delivery. Int J Pharm., 84, 141-50.
Sangeetha, S.; Sakthisaravanan, V.; Komala, M.; Harish, G. and Siva, kV (2004). Design and evaluation of gastroretentive beads of theophylline by ionotropic gelation. Int J Pharmacy and Pharm Sci, 2(3), 99-101.
Shu, X Z. and Zhu, KJ (2000). A novel approach to prepare tripolyphosphate: chitosan complex beads for controlled release drug delivery. International Journal of Pharmaceutics. 2000, 201. 51-58.
Shu, XZ. and Zhu, KJ (2002). Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure. International Journal of Pharmaceutics, 233, 217-225.
Sinha, VR.; Kumria, R (2001). Polysaccharides in colon-specific drug delivery. Int. J. Pharm., 224, 19-38.
Sinha, VR.; Mittal, BR.; Bhutani, KK. and Kumria, R (2004). Colonic drug delivery of 5-fluorouracil: an in vitro evaluation. International Journal of Pharmaceutics, 269, 101-108.
Thakur, S.; Ghanshyam, S. and Chauhan, Ahn. JH (2009). Synthesis of acryloyl guar gum and its hydrogel materials for use in the slow release of L-DOPA and L-tyrosine. Carbohydrate Polymers, 76, 513-520.
Tønnesen, H. H.; and Karlsen, J (2002). Alginate in drug delivery systems. Drug. Dev. Ind. Pharm., 28(6), 621-630.
Tozaki, H.; Komoike, J.; Tada, C.; Maruyama, T.; Terabe, A.; Suzuki, T.; Yamamoto, A.; Muranishi, S (1997). Chitosan capsules for colon-specific drug delivery: improvement of insulin absorption from the rat colon. J. Pharm. Sci., 86, 1016-1021.
Vandamme, Th. F.; Lenourry, A.; Charrueau, C.; and Chaumeil, C (2000). The use of polysaccharides to target drugs to the colon. Carbohydrate Polymers, 48, 219-231.
Vervoort, L.; Mooter, GV.; Augustijns, P. and Kinget, R (1998). Inulin hydrogels. I. Dynamic and equilibrium swelling properties. Int J Pharm., 172, 127-135.
Vervoort, L.; Rombaut, P.; Mooter, GV.; Augustijns, P. and Kinget, R (1998). Inulin hydrogels. II. In vitro degradation study. Int J Pharm., 172, 137-145.
Vyas, SP.; Khar, RK (2002). Systems for colon specific delivery. Controlled drug delivery: Concept and advantages. 1st ed.; Vallabh Prakashan: Delhi, 2002, 218–56.
Wilson, CG,.; Mukherji, G. and Sha, HK (2008). Modified-release Drug Delivery Technology. Biopolymers and Colonic Delivery, 2, 295-309.
Xiaoxia, Li.; Hongguo, Xie.; Junzhang, Lin.; Weiyang Xiea.; and Xiaojun, M (2009). Characterization and biodegradation of chitosan–alginate polyelectrolyte complexes. Polymer Degradation and Stability. 94, 1-6.
