Nanocrystals as Effective Delivery Systems of Poorly Water-soluble Natural Molecules

Natural products are an important source of therapeutically effective compounds throughout the world. Since ancient times, a huge amount of both plant extracts and isolated compounds have been largely employed in treatment and prevention of human disorders and, currently, more than 60% of the world's population trusts on plant medicaments as demonstrated by the increasing quantity of herbal therapeutics in the market. Unfortunately, several promising natural molecules for the treatment of the most diverse ailments are characterized by extremely unfavourable features, such as low water solubility and poor/irregular bioavailability, which hinder their clinical use. To overcome these limitations and to make herbal therapy more effective, different formulative approaches have been employed. Among the different strategies for increasing drug solubility, nanocrystals can be considered one of the most interesting and successful approaches. Drug nanocrystals are nanosized drug particles usually formulated as nanosuspensions, namely submicron dispersions in liquid media where surfactants, polymers, or a mixture of both act as stabilisers. In this review, we described the most significant results and progresses concerning drug nanocrystal formulations for the delivery of natural compounds with a significant pharmacological activity. The text is organized in nine sections, each focusing on a specific poorly water- soluble natural compound (apigenin, quercetin, rutin, curcumin, baicalin and baicalein, hesperetin and hesperidin, resveratrol, lutein, silybin). To foster the clinical translation of these natural nanomedicines, our opinion is that future research should pair the essential pharmacokinetic studies with carefully designed pre-clinical experiments, able to prove the formulation efficacy in relevant animal models in vivo.