Practical approach to development of GS-445124-loaded PLGA nanoparticles for the long-term treatment of feline infectious peritonitis caused by feline coronavirus infection

Abstract

Feline infectious peritonitis virus (FIPV) caused by feline coronavirus (FCoV) infection leads to a high mortality rate when untreated. GS-441524, an antiviral agent effective against FIPV, is orally administered twice daily or through daily subcutaneous injections for approximately 12 weeks. While the short treatment period recuses concerns about adherence, frequent administrations may cause handling-related stress in cats. Therefore, it is essential to develop a long-acting formulation that requires only a single administration. In this study, we used polylactide-co-glycolide (PLGA) as a carrier, which was used to effectively encapsulate GS-441524 with sustained-release functionality and GS-441524-loaded PLGA nanoparticles (GS-PLGA NP) were prepared. The particle size of GS-PLGA NP was 216 nm, the encapsulation efficiency was 78 %, and the 7-day release was 92 %. When GS-PLGA NP was injected at 22 mg/kg in cats, higher systemic exposure can be expected compared to injecting GS-441524 at 4 mg/kg for one week (relative bioavailability, 152 %). As well as GS-PLGA NP showed lower toxicity, improved cellular uptake, and enhanced antiviral efficacy against FCoV compared to the pure GS-441524.

Keywords: Anti-viral effect; Feline infectious peritonitis; GS-441524; Polylactide-co-glycolide; Single-dose acute toxicity.