Cervical
cancer is the fourth most common malignancy among women.
Compared to other types of cancer, therapeutic agents can be administrated
locally at the mucosal vaginal membrane. Thermosensitive gels have
been developed over the years for contraception or for the treatment
of bacterial, fungal, and sexually transmitted infections. These formulations
often carry therapeutic nanoparticles and are now being considered
in the arsenal of tools for oncology. They can also be three-dimensionally
(3D) printed for a better geometrical adjustment to the anatomy of
the patient, thus enhancing the local delivery treatment. In this
study, a localized delivery system composed of a Pluronic F127-alginate
hydrogel with efficient nanoparticle (NP) release properties was prepared
for intravaginal application procedures. The kinetics of hydrogel
degradation and its NP releasing properties were demonstrated with
ultrasmall gold nanoparticles (∼80% of encapsulated AuNPs released
in 48 h). The mucoadhesive properties of the hydrogel formulation
were assayed by the periodic acid/Schiff reagent staining, which revealed
that 19% of mucins were adsorbed on the gel’s surface. The
hydrogel formulation was tested for cytocompatibility in three cell
lines (HeLa, CRL 2616, and BT-474; no sign of cytotoxicity revealed).
The release of AuNPs from the hydrogel and their accumulation in vaginal
membranes were quantitatively measured in vitro/ex vivo with positron emission tomography, a highly sensitive
modality allowing real-time imaging of nanoparticle diffusion (lag
time to start of permeation of 3.3 h, 47% of AuNPs accumulated in
the mucosa after 42 h). Finally, the potential of the AuNP-containing
Pluronic F127-alginate hydrogel for 3D printing was demonstrated,
and the geometrical precision of the 3D printed systems was measured
by magnetic resonance imaging (<0.5 mm precision; deviation from
the design values <2.5%). In summary, this study demonstrates the
potential of Pluronic F127-alginate formulations for the topical administration
of NP-releasing gels applied to vaginal wall therapy. This technology
could open new possibilities for photothermal and radiosensitizing
oncology applications.