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Tetanus Toxoids Loaded Glucomannosylated Chitosan Based Nanohoming Vaccine Adjuvant with Improved Oral Stability and Immunostimulatory Response

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Abstract

Purpose

The present report embarks on rational designing of stable and functionalized chitosan nanoparticles for oral mucosal immunization.

Methods

Stable glucomannosylated sCh-GM-NPs were prepared by tandem cross linking method followed by lyophilization. The in vitro stability of antigen and formulation, cellular uptake and immunostimulatory response were assessed by suitable experimental protocol.

Results

Stability testing ensured the chemical and conformation permanency of encapsulated TT as well as robustness of sCh-GM-NPs in simulated biological media. The antigen release from sCh-GM-NPs followed initial burst followed by controlled Weibull’s type of release profile. The higher intracellular uptake of sCh-GM-NPs in Raw 264.7 and Caco-2 was concentration and time dependent which mainly attributed to Clathrin and receptor mediated endocytosis via mannose and glucose receptor. The in vivo evaluation in animals revealed that sCh-GM-NPs posed significantly (p < 0.001) higher humoral, mucosal and cellular immune response than other counterparts. More importantly, commercial TT vaccine administered through oral or intramuscular route was unable to elicit all type of immune response.

Conclusion

The sCh-GM-NPs could be considered as promising vaccine adjuvant for oral tetanus immunization. Additionally, this technology expected to benefit the design and development of stable peroral formulation for administration of protein, peptides and variety of other antigens.

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Acknowledgments and Disclosures

Authors are grateful to Dr. M. L Mago and Lavit Jambu, Panacea Biotech, Lalru, Punjab, India for gift samples of TT, tetanus antitoxin, and necessary training. Authors are also thankful to Department of Biotechnology (DBT), Govt. of India, India for financial assistance, Council of Scientific and Industrial Research (CSIR) Govt. of India, India for providing fellowship to Mr. AKA, and Director, NIPER, SAS Nagar for providing necessary infrastructure facilities. Technical assistance provided by Mr. Rahul Mahajan in SEM analysis and Mr. Vinod Kumar in TEM analysis is also duly acknowledged.

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Authors and Affiliations

  1. Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, 160 062, India

    Harshad Harde, Ashish Kumar Agrawal & Sanyog Jain

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  1. Harshad Harde
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  2. Ashish Kumar Agrawal
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  3. Sanyog Jain
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Correspondence to Sanyog Jain.

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Harde, H., Agrawal, A.K. & Jain, S. Tetanus Toxoids Loaded Glucomannosylated Chitosan Based Nanohoming Vaccine Adjuvant with Improved Oral Stability and Immunostimulatory Response. Pharm Res 32, 122–134 (2015). https://doi.org/10.1007/s11095-014-1449-5

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