Research ArticleImproved stability and immunological potential of tetanus toxoid containing surface engineered bilosomes following oral administration
Graphical Abstract
GM-bilosomes exhibited significantly higher systemic immune response simultaneously maintaining the chemical and conformation stability of the tetanus toxoid (TT) entrapped in to freeze dried formulations and can be considered as a promising carrier and adjuvant system for oral mucosal immunization.
Section snippets
Materials and reagents
TT (1850 Lf/mL, Batch No. TAM 046) was provided as generous gift sample by Panacea Biotec, India. Tetanus Toxoid (Adsorbed I.P.) (Serum Institute of India Ltd., Batch No. 017I1017B) was purchased from local market. Secondary antibodies namely anti-mouse IgA (α-chain specific) peroxidase conjugate, anti-mouse IgG (γ-chain specific) peroxidase conjugate, 3,3′,5,5′-tetramethylbenzidine (TMB), Nunc Immuno™ Maxisorb F96 well solid plates, Cholesterol (CH), sodium deoxycholate (Na-DOC), Span 80,
Preparation and optimization of vesicular formulations
The size, PDI, zeta potential and entrapment efficiency (EE) of different vesicular formulations are shown in Table 1. Morphology determination by TEM analysis (Figure 1) further confirmed the formation of vesicles of almost spherical shape with smooth surface. The results obtained in TEM analysis were also in good correlation with the results of DLS analysis.
Lyophilization
All vesicular formulations were lyophilized in order to impart long term stability. A number of cryoprotectants (Table 2) were screened
Discussion
In the present report mannosylated bilosomes were proposed for selective uptake and delivery of TT to APCs through the oral route. GM has been reported to exhibit excellent stability against digestive enzymes19, 20 which can also increase the stability of bilosomes in GIT. Furthermore, polymeric nature can provide higher density of mannose molecules over the bilosomes surface which can result in more precise recognition and binding to mannose receptors over expressed on APCs. Therefore, we
Acknowledgment
Authors are thankful to Prof. KB Tikoo and Mr. Vinod Kumar for providing TEM facilities at NIPER. Authors appreciate the technical assistance provided by Mr. Rahul Mahajan.
References (37)
- et al.
Mannosylated niosomes as adjuvant-carrier system for oral genetic immunization against hepatitis B
Immunol Lett
(2005) - et al.
Mannosylated niosomes as adjuvant-carrier system for oral mucosal immunization
J Liposome Res
(2006) - et al.
Lymphocyte migration in the intestinal mucosa: entry, transit and emigration of lymphoid cells and the influence of antigen
Vet Immunol Immunopathol
(1999) - et al.
Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach
J Control Release
(2006) - et al.
Mucosal vaccines: the promise and the challenge
Nat Rev Immunol
(2006) - et al.
Liposome-based delivery system for vaccine candidates: constructing an effective formulation
Nanomedicine
(2012) - et al.
Non-ionic surfactant based vesicles (niosomes) in drug delivery
Int J Pharm
(1998) - et al.
Chitosan microparticles for oral vaccination: preparation, characterization and preliminary in vivo uptake studies in murine Peyer's patches
Biomaterials
(2001) - et al.
Preparation of coated nanoparticles for a new mucosal vaccine delivery system
Int J Pharm
(2005) - et al.
Oral delivery of tetanus toxoid using vesicles containing bile salts (bilosomes) induces significant systemic and mucosal immunity
Methods
(2006)
Advances in lipid-based subunit vaccine formulations
Curr Immunol Rev
Topical and mucosal liposomes for vaccine delivery
Wiley Interdiscip Rev Nanomed Nanobiotechnol
Cholera toxin B subunit conjugated bile salt stabilized vesicles (bilosomes) for oral immunization
Int J Pharm
Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: implications for microbial attachment and oral vaccine targeting
J Exp Med
The uptake and translocation of latex nanospheres and microspheres after oral administration to rats
J Pharm Pharmacol
Targeting to macrophages: role of physicochemical properties of particulate carriers-liposomes and microspheres-on the phagocytosis by macrophages
J Control Release
Development of phosphorylated glucomannan-coated chitosan nanoparticles as nanocarriers for protein delivery
J Nanosci Nanotechnol
Formation of new glucomannan-chitosan nanoparticles and study of their ability to associate and deliver proteins
Macromolecules
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Conflict of Interest and Disclosure: The authors report no financial interest that might pose a potential, perceived, or real conflict of interest.
All sources of support for research: Authors are grateful to the Department of Biotechnology (DBT), Government of India, New Delhi, India for providing support.