Polymeric Nanostructured Systems for Liquid Formulation of Praziquan-tel: Development and in vitro Assessment

Praziquantel (PZQ) is widely used in the treatment of several parasitic infections in both humans and animals, and is the first choice in the treatment of Schistosomiasis in humans. However, PZQ is a hydrophobic drug, and its low aqueous solubility has been a significant barrier to the development of oral liquid formulations that may provide improved bioavailability, pharmacokinetic profile, and compliance. The aim of this study was thus (i) to develop an oil-in-water (O/W) nanoemulsion(NE)-based platform for the delivery of PZQ in liquid form; (ii) to study the transport of PZQ formulated in NEs across an in vitro model of the intestinal epithelium; and (iii) to determine the toxicity profile of the NEs and their individual components on the model epithelium. We also sought to compare the toxicity and transport profiles of the proposed formulations, with those of PZQ in a solid nanostructured particle system - PZQ encapsulated within poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles (NPs). Two essential oils were selected as the oil phase in the NEs, namely clove and orange. The NEs were prepared with selected non-ionic surfactants and had high solubilization capacity towards PZQ, and average diameters well below 100nm. The NEs also showed long term physical stability at both simulated physiological and gastric conditions. NEs with clove oil (NEC-PZQ) were observed to have a lower cytotoxic profile when compared to the orange oil NEs (NEO-PZQ). The results also showed that the transport of PZQ formulated within such nanostructured systems was much greater and larger rates across confluent and polarized Caco-2 monolayers when compared to free PZQ. Interestingly, little difference in PZQ transport between the NEs and NPs was observed. These results point to NEs as potentially viable strategies for the liquid formulation of PZQ in particular, and more broadly to the formulation of other hydrophobic therapeutics that may be employed in the fight against important neglected diseases such as Schistosomiasis, which alone affects more than 240 million people worldwide.