Search

Remdesivir is among the SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) drugs with great potential. However, its poor aqueous solubility restricts its therapeutic action. Therefore, the aim was to develop the nasal delivery of Remdesivir with solubilizing polymers, poloxamer 407, and β-cyclodextrin, which resulted in significant solubility enhancement. In addition, this nanosuspension was developed for the first time for pulmonary delivery to enhance the in vivo performance of remdesivir. Remdesivir solubility and biocompatibility were greatly improved by polymeric encapsulation at the nanoscale. The nanosuspension was prepared by the modified precipitation-ultra sonication process and showed a good particle size 500 nm ± 20 nm, with polydispersity (0.226 ± 0.02) and zeta potential (-16.0 ± 2 mV). The nasal formulation was also assessed for in vitro dissolution and diffusion, in addition to toxicity investigations (Hemolysis, MTT assay). The conversion of remdesivir crystals to an amorphous form was verified by characterization studies (XRD and DSC). The morphology of the nano particles was determined by SEM method and found to be spherical and of uniform shape. FTIR study was performed to determine the drug compatibility with the polymers and was satisfactory. Histopathology study on goat nasal mucosa showed no adverse effects of the formulation on nasal tissues. Analysis using reverse transcription polymerase chain reaction revealed noticeably reduced levels of IL-4 mRNA expression (pro-inflammatory cytokines). In comparison to intravenous delivery, nasal delivery of remdesivir nanosuspension is patient-complaint and easy to use. The outcomes of this study demonstrate the potential for delivering remdesivir nanosuspension via the nasal route. [ABSTRACT FROM AUTHOR]