Evaluation of Solid Lipid Nanoparticles as Carriers for Delivery of Hepatitis B Surface Antigen for Vaccination Using Subcutaneous Route

Dinesh Mishra1, Himanshu Mishra, Pradyumna K. Mishra, Manoj Nahar, Vaibhav Dubey, Narendra K. Jain



Purpose: Solid lipid nanoparticles (SLN) have emerged as carriers for therapeutic peptides, proteins, antigens and bioactive molecules. We have explored the potential of SLN as carrier for Hepatitis B surface antigen (HBsAg) by surface modifications to enhance their loading efficiency and the cellular uptake, using subcutaneous route.

Methods: Four different formulations of SLN were prepared by solvent injection method and characterized for various physical properties: particle size, surface morphology, shape, zeta potential, polydispersity, X-ray diffraction analysis, release profile and entrapment efficiency. HBsAg loaded SLN were studied for their functional characteristics, in vitro cellular uptake and internalization studies by human dendritic cells, macrophages and fibroblasts, T cell proliferation and TH1/TH2 response. Humoral immune response elicited by subcutaneously administered HBsAg containing SLN formulations were studied in vivo in mice.

Results: Compared to soluble HBsAg; SLN, particularly the mannosylated formulation, showed better cellular uptake, lesser cytotoxicity and induction of greater TH1 type of immune response. They also showed better immunological potential by producing sustained antibody titer.

Conclusion: Mannosylated SLN appears to be promising as carrier for vaccine delivery against hepatitis B as ascertained by in vitro and in vivo studies, however further investigations on humans are required to establish their potential as vaccines against hepatitis B infection.

J Pharm Pharm Sci, 13 (4): 495-509, 2010

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DOI: http://dx.doi.org/10.18433/J3XK53