Preparation of Mesalazine-Clay Composite Encapsulated Alginate (MCA) Bead for Targeted Drug Delivery: Effect of Composite Content and CaCl2 Concentration

Hye-Jin Hong; Hyeon Su Jeong; Ki-Min Roh; Ilmo Kang

Macromolecular Research, Vol.26, No.11, 1019-1025, November, 2018

DOI10.1007/s13233-019-7033-4 Export Citation

Preparation of Mesalazine-Clay Composite Encapsulated Alginate (MCA) Bead for Targeted Drug Delivery: Effect of Composite Content and CaCl2 Concentration

Hye-Jin Hong^†, Hyeon Su Jeong¹, Ki-Min Roh², and Ilmo Kang^{2, †}

Mineral Resources Research Division, Korea Institute of Geoscience and Mineral Resources(KIGAM), Daejeon 34132, Korea
¹Institute of Advanced Composite Materials, Korea Institute of Science and Technology, 92 Chudong ro, Bondong-eup, Wanju-gun, Jeonbuk 55324, Korea
²Advanced Geo-Materials Research Department, Korea Institute of Geoscience and Mineral Resources (KIGAM), Daejeon 34132, Korea

E-mail:,

Mesalazine is a colon target drug used extensively for the treatment of Crohn’s disease. To avoid the side effects as well as insufficient absorption of the drug, targeted release of mesalazine at the site of action, small bowel or colon, should be needed. In the present study, mesalazine-clay composite encapsulated alginate (MCA) beads are synthesized with various concentrations of mesalazine-clay composite (MCC) and cross-linker (CaCl2) for targeted drug delivery. Because of mesalazine intercalation in montmorillonite (MMT) clay and pH-sensitive swelling property of alginate polymer in alkaline condition, MCA beads exhibited a high mesalazine loading efficiency (≈9%) and selective mesalazine release in intestinal condition. The preparation conditions of MCA beads considerably affected drug entrapment efficiency, swelling property, and drug release profile. In particular, increase in MCC content in MCA beads lead to significant improvement in mesalazine loading efficiency and prevented immediate destruction caused by over-swelling of MCA beads in intestinal conditions (pH 7.4). A denser alginate network formed by the immobilization of MCC prevents mesalazine loss in intestinal condition and increases the stability of MCA beads against over-swelling. Finally, an in vitro release test revealed that MCA beads (1 g MCC content, cross-linked with 1 M CaCl2) not only prevented mesalazine release in the gastric condition (< 8%) but also retarded mesalazine release in the intestinal condition. The comprehensive results of this study will provide practical insights into the use of MCA beads for targeted drug delivery.

Keywords:mesalazine;colon target drug delivery;smectite clay;alginate polymer

[References]

Aguzzi C, Capra P, Bonferoni C, Cerezo P, Salcedo I, Sanchez R, Caramella C, Viseras C, Appl. Clay Sci., 50, 106 (2010)
Ashford M, Fell J, J. Drug Targeting, 2, 241 (1994)
Li J, Mooney DJ, Nat. Rev. Mater., 1, 16071 (2016)
Li H, Niu Y, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 89, 160 (2018)
Li H, Niu Y, Int. J. Polym. Mater. Polym. Biomater., 67, 192 (2018)
Kamath KR, Park K, Adv. Drug Deliv. Reviv., 11, 59 (1993)
Ali A, Ahmed S, Int. J. Biol. Macromol., 109, 273 (2018)
Aguero L, Zaldivar-Silva D, Pena L, Dias ML, Carbohydr. Polym., 168, 32 (2017)
Jung J, Arnold RD, Wicker L, Colloids Surf. B: Biointerfaces, 104, 116 (2013)
Paukkonen H, Kunnari M, Lauren P, Hakkarainen T, Auvinen VV, Oksanen T, Koivuniemi R, Yliperttula M, Laaksonen T, Int. J. Pharm., 532, 269 (2017)
Neufeld L, Bianco-Peled H, Int. J. Biol. Macromol., 101, 852 (2017)
Swamy BY, Yun YS, Int. J. Biol. Macromol., 77, 114 (2015)
Trendafilova I, Szegedi A, Yoncheva K, Shestakova P, Mihaly J, Ristic A, Konstantinov S, Popova M, Eur. J. Pharm. Sci., 81, 75 (2016)
Joshi GV, Kevadiya BD, Patel HA, Bajaj HC, Jasra RV, Int. J. Pharm., 374, 53 (2009)
Park JK, Choy YB, Oh JM, Kim JY, Hwang SJ, Choy JH, Int. J. Pharm., 359, 198 (2008)
Hong HJ, Kim JW, Suh YJ, Kim DY, Roh KM, Kang IM, Macromol. Res., 25(11), 1145 (2017)
Gao C, Liu M, Chen J, Zhang X, Polym. Degrad. Stabil., 94, 1405 (2009)
Vityazev FV, Fedyuneva MI, Golovchenko VV, Patova OA, Ipatova EU, Durnev EA, Martinson EA, Litvinets SG, Carbohydr. Polym., 157, 9 (2017)
Ritger PL, Peppas NA, J. Control. Release, 5, 37 (1987)
Castello J, Gallardo M, Busquets MA, Estelrich J, Colloids Surf. Physicochem. Eng. Asp., 468, 151 (2015)
Hu C, Gong R, Zhou F, Int. J. Polym. Sci., 2015, 12 (2015)
Neufeld L, Bianco-Peled H, Int. J. Pharm., 491, 170 (2015)
Hong HJ, Kim BG, Hong J, Ryu J, Ryu T, Chung KS, Kim H, Park IS, Chem. Eng. J., 319, 163 (2017)
Zhang W, Jin X, Li H, Zhang RR, Wu CW, Carbohydr. Polym., 186, 82 (2018)
Amidon S, Brown JE, Dave VS, AAPS Pharm. Sci. Tech., 16, 731 (2015)

[Referenced By]

[1] Aguzzi C, Capra P, Bonferoni C, Cerezo P, Salcedo I, Sanchez R, Caramella C, Viseras C, Appl. Clay Sci., 50, 106 (2010)

[2] Ashford M, Fell J, J. Drug Targeting, 2, 241 (1994)

[3] Li J, Mooney DJ, Nat. Rev. Mater., 1, 16071 (2016)

[4] Li H, Niu Y, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 89, 160 (2018)

[5] Li H, Niu Y, Int. J. Polym. Mater. Polym. Biomater., 67, 192 (2018)

[6] Kamath KR, Park K, Adv. Drug Deliv. Reviv., 11, 59 (1993)

[7] Ali A, Ahmed S, Int. J. Biol. Macromol., 109, 273 (2018)

[8] Aguero L, Zaldivar-Silva D, Pena L, Dias ML, Carbohydr. Polym., 168, 32 (2017)

[9] Jung J, Arnold RD, Wicker L, Colloids Surf. B: Biointerfaces, 104, 116 (2013)

[10] Paukkonen H, Kunnari M, Lauren P, Hakkarainen T, Auvinen VV, Oksanen T, Koivuniemi R, Yliperttula M, Laaksonen T, Int. J. Pharm., 532, 269 (2017)

[11] Neufeld L, Bianco-Peled H, Int. J. Biol. Macromol., 101, 852 (2017)

[12] Swamy BY, Yun YS, Int. J. Biol. Macromol., 77, 114 (2015)

[13] Trendafilova I, Szegedi A, Yoncheva K, Shestakova P, Mihaly J, Ristic A, Konstantinov S, Popova M, Eur. J. Pharm. Sci., 81, 75 (2016)

[14] Joshi GV, Kevadiya BD, Patel HA, Bajaj HC, Jasra RV, Int. J. Pharm., 374, 53 (2009)

[15] Park JK, Choy YB, Oh JM, Kim JY, Hwang SJ, Choy JH, Int. J. Pharm., 359, 198 (2008)

[16] Hong HJ, Kim JW, Suh YJ, Kim DY, Roh KM, Kang IM, Macromol. Res., 25(11), 1145 (2017)

[17] Gao C, Liu M, Chen J, Zhang X, Polym. Degrad. Stabil., 94, 1405 (2009)

[18] Vityazev FV, Fedyuneva MI, Golovchenko VV, Patova OA, Ipatova EU, Durnev EA, Martinson EA, Litvinets SG, Carbohydr. Polym., 157, 9 (2017)

[19] Ritger PL, Peppas NA, J. Control. Release, 5, 37 (1987)

[20] Castello J, Gallardo M, Busquets MA, Estelrich J, Colloids Surf. Physicochem. Eng. Asp., 468, 151 (2015)

[21] Hu C, Gong R, Zhou F, Int. J. Polym. Sci., 2015, 12 (2015)

[22] Neufeld L, Bianco-Peled H, Int. J. Pharm., 491, 170 (2015)

[23] Hong HJ, Kim BG, Hong J, Ryu J, Ryu T, Chung KS, Kim H, Park IS, Chem. Eng. J., 319, 163 (2017)

[24] Zhang W, Jin X, Li H, Zhang RR, Wu CW, Carbohydr. Polym., 186, 82 (2018)

[25] Amidon S, Brown JE, Dave VS, AAPS Pharm. Sci. Tech., 16, 731 (2015)