Development of a thermo-sensitive in situ nasal gel with nanoparticles of poly(lactic-co-glycolic) acid copolymer containing favipiravir

Introduction. Favipiravir is a selective inhibitor of viral RNA polymerase with a broad spectrum of antiviral activity; however, its low aqueous solubility results in reduced oral bioavailability. Therefore, the development of new delivery systems, such as thermosensitive nasal in situ gels, is necessary.

The purpose of the work. To develop and characterize thermosensitive in situ gels based on P407 and P188 for intranasal delivery.

Material and methods. Favipiravir-loaded PLGA nanoparticles were prepared using nanoprecipitation. Particle diameter was deter- mined using dynamic light scattering (DLS) at 25 °C. Thermosensitive gels were prepared using the cold method with varying P407 concentrations and varying the P407/P188 ratio. Rheological properties were measured using a SmartPave 102 rheometer at 10–40 °C and a heating rate of 0.05 °C/sec. In vitro release studies were conducted using a DHC-6T transdermal diffusion tester in phosphate buffer, pH 6.4, at 37 °C, with samples analyzed at six time points using UV spectrophotometry.

Results. The average diameter of favipiravir-loaded PLGA nanoparticles was 168.14±3.49 nm, a suitable size for intranasal delivery via the nose-to-brain mechanism. In situ temperature-sensitive gel studies revealed that as the P407 concentration increased from 18 to 25% by weight, the Tsol-gel decreased from 29.04±0.63 °C to 21.84±0.19 °C. The addition of P188 at an 8/2 ratio (P407/P188) significantly increased the T in the sol-gel by 6.64–8.38 °C compared to systems without P188. The favipiravir release profile from the API suspension was characterized by rapid release (46% in 5 min, 72% in 10 min); from PLGA nanoparticles, by delayed release (17– 29% in 5–10 min, 94% in 120 min); and from the in situ gel with nanoparticles, by the most prolonged release (3–9% in 5–10 min, 65% in 120 min).

Conclusion. An intranasal delivery system consisting of PLGA nanoparticles loaded with favipiravir in a thermosensitive in situ gel ma- trix based on P407 and P188 was developed. A dual release control mechanism (polymer degradation and delayed diffusion from the gel matrix) provides a pronounced prolonged effect.