Purpose: Immunomodulatory and broad-spectrum antiviral activities have motivated the evaluation of curcumin for Coronavirus
infection 2019 (COVID-19) management. Inadequate bioavailability is the main impediment to the therapeutic effects of oral Cur. This
study aimed to develop an optimal curcumin transferosome-loaded thermosensitive in situ gel to improve its delivery to the lungs.
Methods: Transferosomes were developed by using 33 screening layouts. The phospholipid concentration as well as the concentration
and type of surfactant were considered independent variables. The entrapment efficiency (EE%), size, surface charge, and polydispersity
index (PDI) were regarded as dependent factors. A cold technique was employed to develop thermosensitive in-situ gels.
Optimized transferosomes were loaded onto the selected gels. The produced gel was assessed based on shape attributes, ex vivo
permeability enhancement, and the safety of the nasal mucosa. The in vitro cytotoxicity, antiviral cytopathic effect, and plaque assay
(CV/CPE/Plaque activity), and in vivo performance were evaluated after intranasal administration in experimental rabbits.
Results: The optimized preparation displayed a particle size of 664.3 ± 69.3 nm, EE% of 82.8 ± 0.02%, ZP of −11.23 ± 2.5 mV, and
PDI of 0.6 ± 0.03. The in vitro curcumin release from the optimized transferosomal gel was markedly improved compared with that of
the free drug-loaded gel. An ex vivo permeation study revealed a significant improvement (2.58-fold) in drug permeability across nasal
tissues of sheep. Histopathological screening confirmed the safety of these preparations. This formulation showed high antiviral
activity against SARS-CoV-2 at reduced concentrations. High relative bioavailability (226.45%) was attained after the formula
intranasally administered to rabbits compared to the free drug in-situ gel. The curcumin transferosome gel displayed a relatively
high lung accumulation after intranasal administration.
Conclusion: This study provides a promising formulation for the antiviral treatment of COVID-19 patients, which can be evaluated
further in preclinical and clinical studies.