pH-sensitive mesalazine carrier for colon-targeted drug delivery: A two-fold composition of mesalazine with a clay and alginate

Hye-Jin Hong; Jiwoong Kim; Yong Jae Suh; Daeyoung Kim; Ki-Min Roh; Ilmo Kang

Macromolecular Research, Vol.25, No.11, 1145-1152, November, 2017

DOI10.1007/s13233-017-5150-5 Export Citation

pH-sensitive mesalazine carrier for colon-targeted drug delivery: A two-fold composition of mesalazine with a clay and alginate

Hye-Jin Hong^†, Jiwoong Kim, Yong Jae Suh, Daeyoung Kim¹, Ki-Min Roh², and Ilmo Kang^{2, †}

Mineral Resources Research Division, Korea Institute of Geoscience and Mineral Resources (KIGAM), Daejeon 34132, Korea
¹NT-IT, Korea University of Science and Technology, Daejeon 34113, Korea
²Advanced Geo-Materials Research Department, Korea Institute of Geoscience and Mineral Resources (KIGAM), Daejeon 34132, Korea

E-mail:,

The release of mesalazine, an anti-inflammatory drug for Crohn’s disease, should be deferred while delivering along the gastrointestinal tract to maximize drug absorption in the colon. To that end, we intercalated mesalazine into a clay mineral, montmorillonite (MMT), and we encapsulated the resulting composite inside a pHsensitive polymer, an alginate hydrogel bead. Once intercalated between the microscopic MMT layers, the mesalazine is prevented from dissolution during encapsulation into the alginate beads. As the resulting mesalazine-clay-alginate (MCA) bead is covered with a protective alginate layer, the mesalazine does not dissolve in acidic gastric conditions. In in vitro release tests, the MCA beads exhibited less than 5% mesalazine release in gastric solution, while ~20% was released over 7 h in the intestinal condition. Our results demonstrate that the MCA bead is a highly effective, biocompatible means of mesalazine delivery to the colon.

Keywords:targeted drug delivery;side effect;smectite;alginate hydrogel

[References]

Aguzzi C, Capra P, Bonferoni C, Cerezo P, Salcedo I, Sanchez R, Caramella C, Viseras C, Appl. Clay Sci., 50, 106 (2010)
Layer PH, Goebell H, Keller J, Dignass A, Klotz U, Gastroenterology, 108, 1427 (1995)
Omwancha WS, Mallipeddi R, Valle BL, Neau SH, Int. J. Pharm., 441, 343 (2013)
Yang JH, Lee JH, Ryu HJ, Elzatahry AA, Alothman ZA, Choy JH, Appl. Clay Sci., 130, 20 (2016)
Rodrigues LADS, Figueiras A, Veiga F, de Freitas RM, Nunes LCC, da Silva Filho EC, da Silva Leite CM, Colloids Surf. B: Biointerfaces, 103, 642 (2013)
Jayrajsinh S, Shankar G, Agrawal YK, Bakre L, J. Drug Deliv. Sci. Technol., 39, 200 (2017)
Khalil H, Mahajan D, Rafailovich M, Polym. Int., 54, 423 (2005)
Park JK, Choy YB, Oh JM, Kim JY, Hwang SJ, Choy JH, Int. J. Pharm., 359, 198 (2008)
Joshi GV, Kevadiya BD, Patel HA, Bajaj HC, Jasra RV, Int. J. Pharm., 374, 53 (2009)
Song D, Park SJ, Kang HW, Park SB, Han JI, J. Chem. Eng. Data, 58, 2455 (2013)
Tugcu-Demiroz F, Acarturk F, Takka S, Konus-Boyunaga O, Eur. J. Pharm. Biopharm., 67, 491 (2007)
Lin YH, Liang HF, Chung CK, Chen MC, Sung HW, Biomaterials, 26, 2105 (2005)
Ribeiro LNM, Alcantara ACS, Darder M, Aranda P, Araujo-Moreira FM, Ruiz-Hitzky E, Int. J. Pharm., 463, 1 (2014)
Neufeld L, Bianco-Peled H, Int. J. Pharm., 491, 170 (2015)
Ijagbemi CO, Baek MH, Kim DS, J. Hazard. Mater., 166(1), 538 (2009)
Allgayer H, Sonnenbichler J, Kruis W, Paumgartner G, Arzneimittelforschung, 35, 1457 (1985)
Nassar MY, El-Shahat MF, Khalile SM, El-Desawy M, Mohamed EA, J. Therm. Anal. Calorim., 117, 463 (2014)
Hou D, Hu S, Huang Y, Gui R, Zhang L, Tao Q, Zhang C, Tian S, Komarneni S, Ping Q, Appl. Clay Sci., 119, 277 (2016)
Kevadiya GVJBD, Patel HA, Ingole PG, Mody HM, Bajaj HC, J. Biomater. Appl., 25, 161 (2010)
Zorica SBAM, Tomic P, Babic BM, Poharc Logar VA, Dordevic AR, Cupac SB, J. Agr. Sci., 56, 25 (2011)
Pongjanyakul T, Rongthong T, Carbohydr. Polym., 81, 409 (2010)
Østberg T, Graffner C, Int. J. Pharm., 111, 271 (1994)

[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] Layer PH, Goebell H, Keller J, Dignass A, Klotz U, Gastroenterology, 108, 1427 (1995)

[3] Omwancha WS, Mallipeddi R, Valle BL, Neau SH, Int. J. Pharm., 441, 343 (2013)

[4] Yang JH, Lee JH, Ryu HJ, Elzatahry AA, Alothman ZA, Choy JH, Appl. Clay Sci., 130, 20 (2016)

[5] Rodrigues LADS, Figueiras A, Veiga F, de Freitas RM, Nunes LCC, da Silva Filho EC, da Silva Leite CM, Colloids Surf. B: Biointerfaces, 103, 642 (2013)

[6] Jayrajsinh S, Shankar G, Agrawal YK, Bakre L, J. Drug Deliv. Sci. Technol., 39, 200 (2017)

[7] Khalil H, Mahajan D, Rafailovich M, Polym. Int., 54, 423 (2005)

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

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

[10] Song D, Park SJ, Kang HW, Park SB, Han JI, J. Chem. Eng. Data, 58, 2455 (2013)

[11] Tugcu-Demiroz F, Acarturk F, Takka S, Konus-Boyunaga O, Eur. J. Pharm. Biopharm., 67, 491 (2007)

[12] Lin YH, Liang HF, Chung CK, Chen MC, Sung HW, Biomaterials, 26, 2105 (2005)

[13] Ribeiro LNM, Alcantara ACS, Darder M, Aranda P, Araujo-Moreira FM, Ruiz-Hitzky E, Int. J. Pharm., 463, 1 (2014)

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

[15] Ijagbemi CO, Baek MH, Kim DS, J. Hazard. Mater., 166(1), 538 (2009)

[16] Allgayer H, Sonnenbichler J, Kruis W, Paumgartner G, Arzneimittelforschung, 35, 1457 (1985)

[17] Nassar MY, El-Shahat MF, Khalile SM, El-Desawy M, Mohamed EA, J. Therm. Anal. Calorim., 117, 463 (2014)

[18] Hou D, Hu S, Huang Y, Gui R, Zhang L, Tao Q, Zhang C, Tian S, Komarneni S, Ping Q, Appl. Clay Sci., 119, 277 (2016)

[19] Kevadiya GVJBD, Patel HA, Ingole PG, Mody HM, Bajaj HC, J. Biomater. Appl., 25, 161 (2010)

[20] Zorica SBAM, Tomic P, Babic BM, Poharc Logar VA, Dordevic AR, Cupac SB, J. Agr. Sci., 56, 25 (2011)

[21] Pongjanyakul T, Rongthong T, Carbohydr. Polym., 81, 409 (2010)

[22] Østberg T, Graffner C, Int. J. Pharm., 111, 271 (1994)