MODIFIED ORDERED MESOPOROUS SILICA AS A CARRIER FOR PROTEIN-BASED ORAL VACCINES

Ordered mesoporous silicas (OMS) are nanostructured materials with excellent protein
delivery properties. The OMS, known as SBA-15, has shown great potential as a novel protective and
adjuvant carrier for oral vaccine formulations. Under conventional synthesis, SBA-15 exhibits open
cylindrical pores of about 10 nm in diameter that are highly ordered under 2D hexagonal symmetry. In
this work, we synthesized SBA-15 particles with morphological, structural, and textural changes to
further evaluate the adsorption effects on protein-based oral vaccine formulations (protein subunits
and virus-like particles - VLPs).
Conventional SBA-15 is naturally hydrophilic due to the presence of silanol groups (SI-OH) on
its surface. To explore novel interactions with protein structures, the surface was chemically modified
with the hydrophobic functional group phenyl. Fourier transform infrared spectroscopy (FT-IR)
confirmed the successful functionalization by identifying new vibracional bands on material.
Small-angle X-ray scattering (SAXS) measurements showed that the mesostructure order was
preserved and nitrogen adsorption isotherms (NAI) indicated a reduction in the surface parameters,
such as specific surface area decreasing from 710 to 470 m²/g and the mean pore diameter from
9.97 nm to 9.22 nm.
Structural and morphological changes were achieved by varying the synthesis conditions. The
mean mesopore diameter increased to 29.1 nm, which allows the encapsulation of larger molecules
such as tetanus anatoxin or VLPs (typically larger than 20 nm). Despite the restriction of the
mesopore diameter, larger protein structures can also be encapsulated in the macroporosity of the
synthesized materials (>50 nm), which are regions formed by the interstices between the aggregates.
Furthermore, other morphologies were obtained, such as spherical particles with diameters ranging
from 0.19 to 0.79 μm in which the mesopore was comparable to conventional syntheses (9.85 nm)
and cylindrical particles similar to bacillus-like particles with a homogeneous length of 0.77 μm.
As in the case of conventional SBA-15, the modified SBA-15 materials exhibited
characteristics suitable for encapsulating distinct protein structures, potentially preserving their
function after adsorption. These properties make them promising for therapeutic applications, such as
oral vaccines, where the ability to protect functional proteins under denaturing conditions is crucial.
This work was supported by grants #158984/2022-6 from CNPq-Brazil and #2017/17844-8 and
#2022/01951-8 from São Paulo Research Foundation (FAPESP)-Brazil.