Targeted Deliver of Remdesivir Mucoadhesive Nanoparticle for Pulmonary Disorder: Study on Physiochemical Properties, Stability and Cytotoxicity

Background

Pulmonary infections need specific strategies which facilitate drug delivery more directly to the lungs and avert systemic toxicity. However, Remdesivir is an antiviral that is found to be potent but has poor pulmonary deposition with rapid systemic infusion via IV route. PLGA and chitosan based mucoadhesive nanoparticles may target site-specific release, prolonged residence time as well as enhanced therapeutic and safety profile.

Materials and Methods

Nanoparticles were prepared based on the use of PLGA and chitosan, and evaluated for the content of moisture, particle density, and flow properties (Carr’s index, Hausner ratio, angle of repose, etc.,). Cytotoxicity was studied using MTT assay on A549 lung epithelial cells at two concentrations. For stability studies, the formulations were subjected at accelerated (40ºC, 75% RH) and room temperature (25ºC, 60% RH) upto 3 months stability studies and analysed for particle shape, size and encapsulation efficiency data.

Results

Remdesivir loaded nanoparticles demonstrated loss of moisture of 1.19% with acceptable behaviour of flow [Carr’s Index (CI) 18.9%; Hausner ratio: 1.24; angle of repose ~30°]. Formulations showed >65% cell viability at all concentrations, exhibiting dose dependent cytotoxicity. On stability studies, both formulations at either of the storage conditions for three months remained consistent and demonstrated almost similar particle size (140 nm) and slight variation in encapsulation efficiency (81.01-81.98%).

Conclusion

The Remdesivir-loaded PLGA-chitosan mucoadhesive nanoparticles have been found to possess novel, stable, physicochemical properties with good biocompatibility and stability supporting their use as an effective pulmonary drug-delivery system.