Evaluation of lactose stabilized tetanus toxoid encapsulated into alginate, HPMC composite microspheres

Saravanakumar Arthanari; Ponnusamy Renukadevi; Vanitha Saravanakumar

Journal of Industrial and Engineering Chemistry, Vol.20, No.4, 2018-2022, July, 2014

DOI10.1016/j.jiec.2013.09.026 Export Citation

Evaluation of lactose stabilized tetanus toxoid encapsulated into alginate, HPMC composite microspheres

Saravanakumar Arthanari^†, Ponnusamy Renukadevi, and Vanitha Saravanakumar¹

Biotechnology Centre, Anna University of Technology Coimbatore, Coimbatore 641047, Tamil Nadu, India
¹Department of Pharmaceutical Analysis, The Erode College of Pharmacy, Erode, Tamil Nadu, India

E-mail:

The utility of both in vitro and in vivo methods to assess the release pattern of alginate, HPMC (TTAL) composite microspheres containing stabilized tetanus toxoid (TT) vaccine were evaluated. TT was stabilized with different concentrations of stabilizer, lactose (1-5%, w/v) and encapsulated into alginate, HPMC composite microspheres by W/O/W multiple emulsion method. The morphology of the prepared microspheres was smooth and spherical in shape with a diameter of around 10 mm. The in vitro release efficiency of microspheres was evaluated for the period of 70 days. In TTAL microspheres, 4% (w/v) lactose gave good sustained antigen delivery for the period of 70 days. Antigen releases from microspheres were determined by ELISA. Based on the results of in vitro release, the ideal batch of TTAL was used to carry out the in vivo studies by antibody induction method using alum adsorbed tetanus toxoid (CRIT) as standard. The antibody level was measured for about of 9 months and finally with one booster dose after 12 months. In this case, TTAL antibody level was rose up to 3 IU/ml of guinea pig serum and 2.5 IU/ml of guinea pig serum was observed in CRIT after 1 year with second booster dose. This novel approach would be helpful to replace the existing adjuvant alum in future.

Keywords:Tetanus toxoid;Alginate;HPMC composite microspheres;Vaccine delivery systems;Biodegradable polymers

[References]

Vandelaer J, Birmingham M, Gasse F, Kurian M, Shaw C, Garnier S, Vaccine, 21, 3442 (2003)
Roper MH, Vandelaer JH, Gasse FL, Lancet, 370, 1947 (2007)
Global Alliance for Vaccines and Immunisation (GAVI) Fact Sheet No. 169, 2001 March.
Langer R, Methods Enzymol., 73, 56 (1981)
Wise DL, Trantolo DJ, Marino RT, Kitchell JP, Adv. Drug. Deliv. Rev., 1, 19 (1987)
Gilley RM, Proc. Int. Symp. Rel. Bioact. Mater., 15, 123 (1988)
Hora MS, Rana RK, Nunberg JH, Tice TR, Gilley RM, Hudson ME, Nat. Biotechnol., 8, 755 (1990)
Eldridge JH, Staas JK, Meulbroek JA, Tice TR, Gilley RM, Infect. Immunol., 59, 2978 (1991)
Preis, Langer R, J. Immunol. Methods, 28, 193 (1979)
Zhao Z, Leong KW, J. Pharm. Sci., 85(12), 1261 (1996)
Gupta RK, Siber GR, Vaccine, 13, 1263 (1995)
Zheng CH, Gao JQ, Zhang YP, Liang WQ, Biochem. Biophys. Res. Commun., 323(4), 1321 (2004)
Nochos A, Douroumis D, Bouropoulos N, Carbohydr. Polym., 74, 451 (2008)
Cai Z, Shi Z, Sherman M, Sun AM, Hepatology, 10, 855 (1989)
Hertzberg S, Moen E, Vogelsang C, Ostgaard K, Appl. Microbiol. Biotechnol., 43(1), 10 (1995)
Lim F, Moss RD, J. Pharm. Sci., 70, 351 (1981)
Aminabhavi TM, Kulkarni AR, Soppimath KS, Dave AM, Mehta MH, Polym. News, 24, 285 (1999)
Downs EC, Robertson NE, Riss TL, Plunkett MIJ, J. Cell. Physiol., 152, 422 (1992)
Babu VR, Rao KSVK, Sairam M, Naidu BVK, Hosamani KM, Aminabhavi TM, J. Appl. Polym. Sci., 99(5), 2671 (2006)
Almeida PF, Almeida AJ, J. Control. Release, 97, 431 (2004)
Draget KI, Braek GS, Smidsrod O, Int. J. Biol. Macromol., 21, 47 (1997)
Johansen P, Men Y, Audran R, Corradin G, Merkle HP, Gander B, Pharm. Res., 15, 1103 (1998)
Bilati U, Allemann E, Doelker E, Eur. J. Pharm. Biopharm., 59, 375 (2005)
Haque A, Morris ER, Carbohydr. Polym., 22, 161 (1993)
Hirrien M, Chevillard C, Desbrieres J, Axelos MAV, Rinaudo M, Polymer, 39(25), 6251 (1998)
Hirrien M, Desbrieres J, Rinaudo M, Carbohydr. Polym., 31, 243 (1996)
Ibbett RN, Phillip K, Price M, Polymer, 33, 4087 (1992)
Indian Pharmacopoeia Ministry of Health and Family Welfare. Government of India, 2, 1985, p. A39.

[1] Vandelaer J, Birmingham M, Gasse F, Kurian M, Shaw C, Garnier S, Vaccine, 21, 3442 (2003)

[2] Roper MH, Vandelaer JH, Gasse FL, Lancet, 370, 1947 (2007)

[3] Global Alliance for Vaccines and Immunisation (GAVI) Fact Sheet No. 169, 2001 March.

[4] Langer R, Methods Enzymol., 73, 56 (1981)

[5] Wise DL, Trantolo DJ, Marino RT, Kitchell JP, Adv. Drug. Deliv. Rev., 1, 19 (1987)

[6] Gilley RM, Proc. Int. Symp. Rel. Bioact. Mater., 15, 123 (1988)

[7] Hora MS, Rana RK, Nunberg JH, Tice TR, Gilley RM, Hudson ME, Nat. Biotechnol., 8, 755 (1990)

[8] Eldridge JH, Staas JK, Meulbroek JA, Tice TR, Gilley RM, Infect. Immunol., 59, 2978 (1991)

[9] Preis, Langer R, J. Immunol. Methods, 28, 193 (1979)

[10] Zhao Z, Leong KW, J. Pharm. Sci., 85(12), 1261 (1996)

[11] Gupta RK, Siber GR, Vaccine, 13, 1263 (1995)

[12] Zheng CH, Gao JQ, Zhang YP, Liang WQ, Biochem. Biophys. Res. Commun., 323(4), 1321 (2004)

[13] Nochos A, Douroumis D, Bouropoulos N, Carbohydr. Polym., 74, 451 (2008)

[14] Cai Z, Shi Z, Sherman M, Sun AM, Hepatology, 10, 855 (1989)

[15] Hertzberg S, Moen E, Vogelsang C, Ostgaard K, Appl. Microbiol. Biotechnol., 43(1), 10 (1995)

[16] Lim F, Moss RD, J. Pharm. Sci., 70, 351 (1981)

[17] Aminabhavi TM, Kulkarni AR, Soppimath KS, Dave AM, Mehta MH, Polym. News, 24, 285 (1999)

[18] Downs EC, Robertson NE, Riss TL, Plunkett MIJ, J. Cell. Physiol., 152, 422 (1992)

[19] Babu VR, Rao KSVK, Sairam M, Naidu BVK, Hosamani KM, Aminabhavi TM, J. Appl. Polym. Sci., 99(5), 2671 (2006)

[20] Almeida PF, Almeida AJ, J. Control. Release, 97, 431 (2004)

[21] Draget KI, Braek GS, Smidsrod O, Int. J. Biol. Macromol., 21, 47 (1997)

[22] Johansen P, Men Y, Audran R, Corradin G, Merkle HP, Gander B, Pharm. Res., 15, 1103 (1998)

[23] Bilati U, Allemann E, Doelker E, Eur. J. Pharm. Biopharm., 59, 375 (2005)

[24] Haque A, Morris ER, Carbohydr. Polym., 22, 161 (1993)

[25] Hirrien M, Chevillard C, Desbrieres J, Axelos MAV, Rinaudo M, Polymer, 39(25), 6251 (1998)

[26] Hirrien M, Desbrieres J, Rinaudo M, Carbohydr. Polym., 31, 243 (1996)

[27] Ibbett RN, Phillip K, Price M, Polymer, 33, 4087 (1992)

[28] Indian Pharmacopoeia Ministry of Health and Family Welfare. Government of India, 2, 1985, p. A39.