Development of favipiravir loaded PLGA nanoparticles entrapped in in-situ gel for treatment of Covid-19 via nasal route

• Published in: Journal of drug delivery science and technology 2023-01, Vol.79, p.104082-104082, Article 104082
• Main Authors: Gattani, Vaishnavi, Dawre, Shilpa
• Format: Article
• Language: English
• Subjects: Box-behnken design; Favipiravir; Mucoadhesion; Nasal ex vivo permeation; PLGA Nanoparticles; Thermoreversible in-situ gel
• ISSN: 1773-2247; 2588-8943
• DOI: 10.1016/j.jddst.2022.104082

In 2019 the emergence of SARS-COV-2 caused pandemic situation worldwide and claimed ∼6.4 M lives (WHO 2022). Favipiravir (FAV) is recommended as a therapy for Covid-19 which belongs to BCS class III with a short half-life of 2–5.5h. Thus, the objective of current study was the development of favipiravir loaded PLGA nanoparticles (NPs) by box-behnken design. Moreover, these NPs were entrapped in thermosensitive gel to increase the permeation through nasal route. The nanoparticles exhibit particle size of 175.6 ± 2 nm with >70 ± 0.5 %EE. NPs showed PDI (0.130) and zeta potential (−17.1 mV) suggesting homogeneity and stability of NPs. DSC, XRD, and FTIR studies concluded absence of any interaction of FAV and the excipients. SEM and AFM studies demonstrated spherical morphology of NPs with smooth surface. The NPs entrapped in-situ gel showed clarity and pH 5.5–6.1. The gelation temperature of NPs dispersed in-situ gel was found in the range of 35 °C −37 °C. The gel has viscosity in range of 34592–4568 cps. The texture analysis profile of gel showed good gelling properties. Dissolution study suggested a sustained release of FAV from NPs (24h) and NPs dispersed gel (32h) as compared to FAV solution (4h). The gel showed good mucoadhesion properties (9373.9 dyne/cm2). Ex-vivo permeation through nasal mucosa of goat elucidated NPs dispersed gel demonstrated significantly higher permeation than solution and NPs. Therefore, it would be a prospective formulation to combat Covid-19 infection with high patient compliance. [Display omitted] •Favipiravir loaded PLGA nanoparticles were successfully developed and optimized using box-benkhen design.•Stable nanoparticle with an entrapment efficiency >70% and particle size 175.6 ± 2 nm was developed successfully.•FAV-NPs dispersed thermoreversible in-situ gel was developed and characterized.•Nanoparticles and NPs in thermoreversible in-situ gel showed a prolonged release profile of FAV.•Ex vivo permeation studies revealed in-situ gel demonstrated higher permeation than nanoparticles and solution.