Monolein Aqueous Dispersions as a Tool to Increase Flavonoids Solubility: A Preliminary Study

Background: Topical application of flavonoids has recently received increased attention, however their use is limited due to a low aqueous solubility and related low in vivo absorption. Unsaturated long-chain monoglycerides emulsified in water, such as monoolein, lead to aqueous nanostructured dispersions of complex lyotropic liquid crystalline phases (lamellar, hexagonal, and cubic structure) able to carry lipophilic molecules^1-2. To potentially solve solubility problems of these molecules, and possibly to facilitate a topical application, the use of monoolein aqueous dispersions (MAD) was investigated on two model flavonoids, namely quercetin (QT) and rutin (RU).

Experimental: MAD were produced by emulsifying monoolein in water in the presence of sodium cholate used at two different concentrations, namely 0.15% and 0.25% with respect to the total weight of the formulation¹. In addition increasing concentrations of flavonoids were tested. MAD were then characterized in terms of size, morphology and drug content by mean of PCS, SDFFS, cryo-TEM and UV spectroscopy. Moreover in vitro studies concerning the drug release modalities, the cytotoxicity and the antioxidant activity of the produced MAD were also conducted.

Results and Discussion: MAD size was found around 250 nm. Cryo-TEM showed that the content of sodium cholate influences the morphological aspect of the MAD. Indeed MAD015 appear as a mixture of vesicles and cubic structures, whilst MAD025 are mainly characterized by unilamellar vesicular structures. Concerning drug content it was found that MAD025 increased at least 80-fold QT solubility, while the same was not found for RU. In addition, in vitro Franz cell experiments showed that the MAD are suitable for cutaneous application while experiments on antioxidant activity demonstrated the two-fold power of QT as compared to RU.

Conclusions: MAD can be potentially proposed for the delivery of the antioxidant molecule QT, whilst many studies have to be performed for finding a way to deliver RU.

References:

1. Esposito et al. Eur J Pharm Biopharm 80:306-312,2012.
2. Esposito et al. Mater Sci Eng C 33:4923–34,2013.

Acknowledgements: This study was funded by Unife FIR2018