화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Macromolecular Research, Vol.27, No.3, 215-226, March, 2019
DOI10.1007/s13233-019-7042-3  Export Citation
Efficient Mucosal Immunization by Mucoadhesive and pH-Sensitive Polymeric Vaccine Delivery System
Lei Xing1, 2, Tian-Jiao Zhou1, Ya-Tong Fan1, Yu-jing He1, Tao Pang1, 3, Ki-Hyun Cho4, Jin-Jian Lu5, Hu-Lin Jiang1, 2, †, and Chong-Su Cho6, †
  • 1State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, P. R. China
  • 2Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing 210009, P. R. China
  • 3Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, P. R. China
  • 4Department of Plastic Surgery, Cleveland Clinic, Cleveland, Ohio 44195, USA
  • 5State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, P. R. China
  • 6Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea
E-mail:,
Mucosal surfaces as the largest immune organ of human body cover 400 m2 of the body including the gastrointestinal, urogenital, and respiratory tracts. The local mucosal immunity is an important first line of defense against many pathogens because most pathogens initiate their infection through access to the mucosal region of body. Also, the mucosal vaccines induce mucosal and systemic immunity simultaneously. Therefore, attracted by the advantages of mucosal immunity, researchers keep an eye on the mucoadhesive and pH-sensitive polymeric vaccine delivery system to solve several limitations of mucosal administration, making mucosal immunity receive great interests lately. In this review, we discuss natural polymer- and synthetic polymer-based mucoadhesive and pH-sensitive systems used for mucosal vaccine delivery. Also, we cover how to target antigen presenting cells and M cells for the cell specificity. Finally, we conclude the significant progress in mucosal vaccine and the prospect mucosal vaccine research in the future.
Keywords:mucosal immunization;mucoadhesive polymer;pH-sensitive;vaccine delivery;M cell targeting
  1. Rappuoli R, Mandl CW, Black S, De Gregorio E, Nat. Rev. Immunol., 11, 865 (2011)
  2. Alter G, Sekaly RP, Vaccine, 33, B55 (2015)
  3. Singh B, Maharjan S, Cho KH, Cui L, Park IK, Choi YJ, Cho CS, Int. J. Biol. Macromol., 110, 54 (2018)
  4. Pulendran B, Li S, Nakaya HI, Immunity, 33, 516 (2010)
  5. K. Hase, K. Kawano, T. Nochi, G. S. Pontes, S. Fukuda, M. Ebisawa, et al., Nature, 462, 226 (2009)
  6. Holmgren J, Czerkinsky C, Eriksson K, Mharandi A, Vaccine, 21, S89 (2003)
  7. Simecka JW, Adv. Drug Deliv. Rev., 34, 235 (1998)
  8. Kaur L, Sharma A, Yadav AK, Mishra N, Artif. Cells Nanomed. Biotechnol., 7, 1 (2017)
  9. Singh B, Maharjan S, Jiang T, Kang SK, Choi YJ, Cho CS, Mol. Pharm., 12, 3816 (2015)
  10. Kang ML, Cho CS, Yoo HS, Biotechnol. Adv., 27, 857 (2009)
  11. Merkus FW, Verhoef JC, Schipper NG, Marttin E, Adv. Drug Deliv. Rev., 29, 13 (1998)
  12. Sarkar MA, Pharm. Res., 9, 1 (1992)
  13. Islam MA, Park TE, Reesor E, Cherukula K, Hasan A, Firdous J, Singh B, Kang SK, Choi YJ, Park IK, Cho CS, Curr. Pharm. Des., 21, 4285 (2015)
  14. Vela Ramirez JE, Sharpe LA, Peppas NA, Adv. Drug Deliv. Rev., 114, 116 (2017)
  15. Pavot V, Rochereau N, Genin C,Verrier B, Paul S, Vaccine, 30, 142 (2012)
  16. Holmgren J, Svennerholm AM, Curr. Opin. Immunol., 24, 343 (2012)
  17. Pelaseyed T, Bergstrom JH, Gustafsson JK, Ermund A, Birchenough GM, et al., Immunol. Rev., 260, 8 (2014)
  18. Renukuntla J, Vadlapudi AD, Patel A, Boddu SH, Mitra AK, Int. J. Pharm., 447, 75 (2013)
  19. Mestecky J, Russell MW, Elson CO, J. Immunol., 179, 5633 (2007)
  20. Wang B, in Oral Bioavailability: Basic Principles, Advanced Concepts, and Applications, John Wiley & Son, Inc., Hoboken, p.21 2011.
  21. Pathak K, Int. J. Pharm. Investig., 1, 62 (2011)
  22. Shaikh R, Singh TRR, Garland MJ, Woolfson AD, Donnelly RF, J. Pharm Bioallied Sci., 1, 3 (2011)
  23. Demirdirek B, Uhrich KE, Int. J. Pharm., 1-2, 528 (2017)
  24. Leung SHS, Robinson JR, J. Control. Release, 5, 223 (1987)
  25. Seok H, Jo YY, Kweon HY, Kim SG, Kim MK, Chae WS, Tissue Eng. Regen. Med., 14, 221 (2017)
  26. Somekawa S, Mahara A, Masutani K, Kimura Y, Urakawa H, Yamaoka T, Tissue Eng. Regen. Med., 14, 507 (2017)
  27. Cho KH, Singh B, Maharjan S, Jang Y, Choi YJ, Cho CS, Tissue Eng. Regen. Med., 14, 211 (2017)
  28. Bang S, Jung UW, Noh I, Tissue Eng. Regen. Med., 15, 25 (2018)
  29. Boddupalli BM, Mohammed ZNK, Nath RA, Banji D, J. Adv. Pharm. Technol. Res., 1, 381 (2011)
  30. Lee HB, Yoon SY, Singh B, Oh SH, Cui L, Yan C, Kang SK, Choi YJ, Cho CS, Tissue Eng. Regen. Med., 15, 1 (2018)
  31. Suckow MA, Jarvinen LZ, HogenEsch H, Park K, Bowersock TL, J. Control. Release, 85, 227 (2002)
  32. Chidambaram M, Krishnasamy K, Nano Biomed. Eng., 5, 28 (2013)
  33. Chattopadhyay S, Chen JY, Chen HW, Hu CJ, Nanotheranostics, 1, 244 (2017)
  34. Farhadian A, Dounighi NM, Avadi M, Hum. Vaccin. Immunother., 11, 2811 (2015)
  35. Spinner JL, Oberoi HS, Yorgensen YM, Poirier DS, Burkhart DJ, Plante M, Evans JT, Vaccine, 33, 5845 (2015)
  36. Jiang HL, Park IK, Shin NR, Yoo HS, Akaike T, Cho CS, Arch. Pharm. Res., 27, 346 (2004)
  37. Jiang HL, Park IK, Shin NR, Kang SG, Yoo HS, Kim SI, Suh SB, Akaike T, Cho CS, Eur. J. Pharm. Biopharm., 58, 471 (2004)
  38. Jiang HL, Kang ML, Quan JS, Kang SG, Akaike T, Yoo HS, Cho CS, Biomaterials, 29, 1931 (2008)
  39. Bucarey SA, Pujol M, Poblete J, Nunez I, Tapia CV, Neira-Carrillo A, Martinez J, Bassa O, Virol. J., 11, 1 (2014)
  40. Kaur K, Sodhi RK, Katyal A, Aneja R, Jain UK, Katare OP, Madan J, Colloids Surf. B: Biointerfaces, 132, 225 (2015)
  41. Chen H, Torchilin V, Langer R, Pharm. Res., 13, 1378 (1996)
  42. Zheng X, Huang Y, Zheng C, Dong S, Liang W, AAPS J., 12, 519 (2010)
  43. Alpar HO, Somavarapu S, Atuah KN, Bramwell VW, Adv. Drug Deliv. Rev., 57, 411 (2005)
  44. Li XY, Kong XY, Shuai S, Zheng XL, Gang G, Wei YQ, Qian ZY, BMC Biotechnol., 8, 89 (2008)
  45. Zhao K, Zhang Y, Zhang X, Li W, Shi C, Guo C, Dai C, Chen Q, Jin Z, Zhao Y, Cui H, Wang Y, Int. J. Nanomedicine, 9, 389 (2014)
  46. Xu W, Shen Y, Jiang Z, Wang Y, Chu Y, Xiong S, Vaccine, 22, 3603 (2004)
  47. Zhou X, Liu B, Yu X, Zha X, Zhang X, Chen Y, Wang X, Jin Y, Wu Y, Chen Y, J. Control. Release, 121, 200 (2007)
  48. Heuking S, Borchard G, J. Pharm. Sci., 101, 1166 (2012)
  49. Klemm D, Heublein B, Fink HP, Bohn A, Angew. Chem.-Int. Edit., 44, 3358 (2005)
  50. Kamel S, Kamel S, Express Polym. Lett., 2, 758 (2008)
  51. Maharaj I, Nairn JG, Campbell JB, J. Pharm. Sci., 73, 39 (1984)
  52. Lazzell V, Waldman RH, Rose C, Khakoo R, Jacknowitz A, Howard S, J. Biol. Stand., 13, 315 (1984)
  53. Lin SY, Tzan YL, Lee CJ, Weng CN, J. Microencapsul., 8, 317 (1991)
  54. Lin SY, Tzan YL, Weng CN, Lee CJ, J. Microencapsul., 8, 537 (1991)
  55. Song Y, Zhou Y, van Drunen Littelvan den Hurk S, Chen L, Biomaterials Sci., 2, 1440 (2014)
  56. Wang H, Roman M, Nanomed-Nanotechnol., 12, 489 (2016)
  57. Pieler MM, Frentzel S, Bruder D, Wolff MW, Reichl U, Vaccine, 34, 6367 (2016)
  58. Tafaghodi M, Sajaditabasi SA, Jaafari MR, J. Biomater. Sci-Polym. E, 17, 909 (2006)
  59. Tafaghodi M, Eskandari M, Iran. J. Basic Med. Sci., 15, 873 (2012)
  60. O'Hagan D, Pavesio A, U. S. Patent 794730982 (2011).
  61. Fan Y, Sahdev P, Ochyl LJ, Akerberg J, Moon JJ, J. Control. Release, 208, 121 (2015)
  62. Wojtasz J, Carlstedt J, Fyhr P, Kocherbitov V, Carbohydr. Polym., 135, 225 (2016)
  63. Edman P, Bjork E, Ryden L, J. Control. Release, 21, 165 (1992)
  64. Elvira C, Mano JF, San RJ, Reis RL, Biomaterials, 23, 1955 (2002)
  65. Illum L, Farraj NF, Davis SS, Johansen BR, O'Hagan DT, Int. J. Pharm., 63, 207 (1990)
  66. Sturesson C, Degling WL, J. Control. Release, 68, 441 (2000)
  67. Deore KL, Thombre NA, Gide PS, J. Pharm. Res., 6, 158 (2013)
  68. Rohit M, Anuj C, Pooja S, Pravin P, J. Adv. Pharm.Technol. Res., 4, 31 (2013)
  69. Kenechukwu FC, Momoh MA, Int. J. Pharm. Investig., 6, 69 (2016)
  70. Dillen K, Vandervoort J, Van den Mooter G, Ludwig A, Int. J. Pharm., 314, 72 (2006)
  71. Quan JS, Jiang HL, Kim EM, Jeong HJ, Choi YJ, Guo DD, Yoo MK, Lee HG, Cho CS, Int. J. Pharm., 359, 205 (2008)
  72. Shastri PN, Kim MC, Quan FS, D'Souza MJ, Kang SM, J. Pharm. Sci., 101, 3623 (2012)
  73. Hori M, Onishi H, Machida Y, Int. J. Pharm., 297, 223 (2005)
  74. Zhao K, Zhang Y, Zhang X, Li W, Shi C, Guo C, Dai C, Chen Q, Jin Z, Zhao Y, PLoS One, 7, e53314 (2012)
  75. Li HS, Singh B, Park TE, Hong ZS, Kang SK, Cho CS, Choi YJ, Eur. J. Pharm. Sci., 80, 16 (2015)
  76. Li Z, Xiong F, He J, Dai X, Wang G, Eur. J. Pharm. Biopharm., 109, 24 (2016)
  77. Li HS, Shin MK, Singh B, Marharjan S, Park TE, Kang SK, Yoo HS, Hong ZS, Cho CS, Choi YJ, J. Control. Release, 233, 114 (2016)
  78. Yoo MK, Kang SK, Choi JH, Park IK, Na HS, Lee HC, Kim EB, Lee NK, Nah JW, Choi YJ, Biomaterials, 31, 7738 (2010)
  79. Jepson MA, Clark MA, Trends Microbiol., 6, 359 (1998)
  80. Sansonetti PJ, Phalipon A, Semin. Immunol., 11, 193 (1999)
  81. Islam MA, Firdous J, Choi YJ, Yun CH, Cho CS, Int. J. Nanomedicine, 7, 6077 (2012)
  82. Jiang T, Singh B, Li HS, Kim YK, Kang SK, Nah JW, Choi YJ, Cho CS, Biomaterials, 35, 2365 (2014)
  83. Singh B, Maharjan S, Jiang T, Kang SK, Choi YJ, Cho CS, Biomaterials, 59, 144 (2015)
  84. Singh B, Maharjan S, Tao J, Kang SK, Choi YJ, Cho CS, Mol. Pharm., 12, 310 (2015)
  85. Taylor RT, Patel SR, Lin E, Butler BR, Lake JG, Newberry RD, Williams IR, J. Immunol., 178, 5659 (2007)
  86. Maharjan S, Singh B, Jiang T, Yoon SY, Li HS, Kim G, Gu MJ, Kim SJ, Park OJ, Han SH, Biomaterials, 84, 286 (2016)
  87. Hase K, Kawano K, Nochi T, Pontes GS, Fukuda S, Ebisawa M, Kadokura K, Tobe T, Fujimura Y, Kawano S, Nature, 462, 226 (2009)