Formulation and Characterization of Nanoemulsion Intranasal
Adjuvants: Effects of Surfactant Composition on Mucoadhesion and Immunogenicity
- Publication date
- Publisher
Abstract
The development of effective intranasal
vaccines is of great interest
due to their potential to induce both mucosal and systemic immunity.
Here we produced oil-in-water nanoemulsion (NE) formulations containing
various cationic and nonionic surfactants for use as adjuvants for
the intranasal delivery of vaccine antigens. NE induced immunogenicity
and antigen delivery are believed to be facilitated through initial
contact interactions between the NE droplet and mucosal surfaces which
promote prolonged residence of the vaccine at the site of application,
and thus cellular uptake. However, the details of this mechanism have
yet to be fully characterized experimentally. We have studied the
physicochemical properties of the NE droplet surfactant components
and demonstrate that properties such as charge and polar headgroup
geometry influence the association of the adjuvant with the mucus
protein, mucin. Association of NE droplets with mucin <i>in vitro</i> was characterized by various biophysical and imaging methods including
dynamic light scattering (DLS), zeta potential (ZP), and surface plasmon
resonance (SPR) measurements as well as transmission electron microscopy
(TEM). Emulsion surfactant compositions were varied in a systematic
manner to evaluate the effects of hydrophobicity and polar group charge/size
on the NE–mucin interaction. Several cationic NE formulations
were found to facilitate cellular uptake of the model antigen, ovalbumin
(OVA), in a nasal epithelial cell line. Furthermore, fluorescent images
of tissue sections from mice intranasally immunized with the same
NEs containing green fluorescent protein (GFP) antigen demonstrated
that these NEs also enhanced mucosal layer penetration and cellular
uptake of antigen <i>in vivo</i>. NE–mucin interactions
observed through biophysical measurements corresponded with the ability
of the NE to enhance cellular uptake. Formulations that enhanced antigen
uptake <i>in vitro</i> and <i>in vivo</i> also
led to the induction of a more consistent antigen specific immune
response in mice immunized with NEs containing OVA, linking NE-facilitated
mucosal layer penetration and cellular uptake to enhancement of the
immune response. These findings suggest that biophysical measurement
of the mucoadhesive properties of emulsion based vaccines constitutes
an effective <i>in vitro</i> strategy for selecting NE candidates
for further evaluation <i>in vivo</i> as mucosal adjuvants