Lyotropic liquid crystal emulsions of LAVR-289: Influence of internal mesophase structure on cytotoxicity and in-vitro antiviral activity

Abstract

Emerging and reemerging viruses pose significant public health threats, underscoring the urgent need for new antiviral drugs. Recently, a novel family of antiviral acyclic nucleoside phosphonates (ANP) composed of a 4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl phosphonic acid skeleton (O-DAPy nucleobase) has shown promise. Among these, LAVR-289 stands out for its potent inhibitory effects against various DNA viruses. Despite its efficacy, LAVR-289s poor water solubility hampers effective drug delivery. To address this, innovative delivery systems utilizing lipidic derivatives have been explored for various administration routes. Submicron lyotropic liquid crystals (LLCs) are particularly promising drug carriers for the encapsulation, protection, and delivery of lipophilic drugs like LAVR-289.This study focuses on developing submicron-sized lipid mesophase dispersions, including emulsified L2 phase, cubosomes, and hexosomes, by adjusting lipidic compounds such as Dimodan® U/J, Lecithins E80, and Miglyol® 812 N. These formulations aim to enhance the solubility and bioavailability of LAVR-289. In vitro evaluations demonstrated that LAVR-289-loaded LLCs at a concentration of 1 µM efficiently inhibited vaccinia virus in infected human cells, with no observed cytotoxicity. Notably, hexosomes exhibited the most favorable antiviral outcomes, suggesting that the internal mesophase structure plays a critical role in optimizing the therapeutic efficacy of this drug class.