Lyotropic liquid crystal emulsions of LAVR-289: Influence of internal mesophase structure on cytotoxicity and in-vitro antiviral activity
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.
Download the full article as PDF here Lyotropic liquid crystal emulsions of LAVR-289
or read it here
Materials
The active antiviral molecule LAVR-289 (Fig. 1), (Z)-2-[(2,6-diaminopyrimidin-4-yl)oxymethyl]-4-[3-hexadecoxypropoxy (isopropoxycarbonyloxy-methoxy)phosphoryl]but-2′-enyl] acetate, was synthesized as previously described (Pradère et al., 2011). Compounds for mesophase dispersion compositions were used as received. Dimodan® U/J (DU), a commercial-grade form of monolinolein, was used as the structuring lipid. This was kindly supplied by Danisco A/S (Brabrand, Denmark) and consists of 96 % distilled monoglycerides (62 % monolinoleates). Medium-chain triglycerides (Miglyol® 812 N) and egg lecithin (Lipoid® E80) were generously provided by IOI Oleo GmbH and Lipoid GmbH, respectively. Steric stabilization of the dispersions was achieved using the emulsifier triblock copolymer Pluronic F127 (PEO99-PPO67-PEO99). Both F127 and Tween 80 were supplied by Sigma Aldrich.
Mathias Brouillard, Thomas Mathieu, Samuel Guillot, Fabienne Méducin, Vincent Roy, Elie Marcheteau, Franck Gallardo, François Caire-Maurisier, Patrick Favetta, Luigi A. Agrofoglio, Lyotropic liquid crystal emulsions of LAVR-289: Influence of internal mesophase structure on cytotoxicity and in-vitro antiviral activity, International Journal of Pharmaceutics, 2024, 124683, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.124683.
Are you looking for excipients in commercial quantities?
