Development of Adjuvanted Solid Fat Nanoemulsions for Pulmonary Hepatitis B Vaccination

J Pharm Sci. 2018 Jun;107(6):1701-1712. doi: 10.1016/j.xphs.2018.02.007. Epub 2018 Feb 15.

Abstract

Pulmonary vaccination is one of the most promising routes for immunization owing to its noninvasive nature and induction of strong mucosal immunity and systemic response. In the present study, recombinant hepatitis B surface antigen loaded solid fat nanoemulsions (SFNs) as carrier system and monophosphoryl lipid A as an adjuvant-carrier system was prepared and evaluated as multiadjuvanted vaccine system for deep pulmonary vaccination. Deposition and clearance from the deep lung of rats were determined by gamma scintigraphy. Biodistribution of SFNs was determined by the live animal imaging system. SFNs dispersion showed slower clearance as compared with sodium pertechnetate control solution (∗∗∗p <0.001) from the pulmonary region due to the virtue of particulate and hydrophobic nature of formulations. Humoral (sIgA and IgG) and cellular (IL-2 and IF-γ) immune responses were found to be significant (∗∗∗p <0.001) when compared with naïve antigen (recombinant surface antigen without any excipient) solution. Data indicate that deep pulmonary immunization offers a stronger immune response with balanced humoral, mucosal, and cellular immunization, which further needs to be tested in higher animals to support this hypothesis for clinical translation of this so far neglected yet potential target tissue for immunization.

Keywords: IVIS imaging system; biodistribution; deep lung delivery; gamma scintigraphy; solid fat nanoemulsions.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / pharmacokinetics
  • Adjuvants, Immunologic / pharmacology
  • Administration, Inhalation
  • Animals
  • Female
  • Hepatitis B / immunology
  • Hepatitis B / prevention & control*
  • Hepatitis B Surface Antigens / administration & dosage*
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B Vaccines / administration & dosage*
  • Hepatitis B Vaccines / immunology
  • Hepatitis B Vaccines / pharmacokinetics
  • Hepatitis B virus / immunology
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunity, Mucosal
  • Lipid A / administration & dosage
  • Lipid A / analogs & derivatives*
  • Lipid A / immunology
  • Lipid A / pharmacokinetics
  • Lung / immunology
  • Lung / metabolism
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution
  • Vaccination / methods

Substances

  • Adjuvants, Immunologic
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Lipid A
  • monophosphoryl lipid A