Enhanced penetration and improved therapeutic efficacy of bexarotene via topical liposomal gel in imiquimod induced psoriatic plaque model in BALB/c mice

Abstract

Bexarotene is a retinoid X receptor agonist originally approved for anti-cancer activity, which was found to have anti-psoriatic activity in recent studies. However, its poor water solubility and high log P makes it difficult to deliver via topical route. Incorporation of bexarotene into liposome will address this issue by improving the solubility and permeability of the drug. In this study, bexarotene liposomes were prepared by optimization of different parameters including lipid to cholesterol ratio, sonication time, percent drug loading and entrapment efficiency. Optimized liposomes of particle size and size distribution (67.8.2 ± 7.15 nm, 0.26 ± 0.02 PDI) with greater than 90% entrapment efficiency were incorporated into gel and tested for rheological behaviour and drug release. Dermal uptake studies of dye loaded liposomes showed improved penetration compared to plain dye. Pharmacodynamic studies performed by employing imiquimod induced psoriatic plaque model in BALB/c mice confirmed effective reversal of psoriasis from liposomal bexarotene as indicated by reduced scaling, inflammation without any toxicity. Further histopathological and cytokine level changes also confirmed the recovery of animals treated with liposomal gel formulation. These results concluded that, formulating bexarotene into liposomal gel improved anti-psoriatic efficacy of the drug.