Evaluation of β-lapachone-methyl-β-cyclodextrin inclusion complex prepared by spray drying and its application against different developmental stages of Schistosoma mansoni in murine model.

Background: β-lapachone (β-lap) is a naphthoquinone widely found in species of vegetables. However, its poor aqueous solubility limits its systemic administration and clinical applications in vivo. To overcome this limitation, several studies have been carried out in order to investigate techniques that can enhance the solubility and dissolution rate of β-lap, such as the use of inclusion complexes with cyclodextrin.

Purpose: To evaluate the in vivo effect of β-lap complexed in methyl-β-cyclodextrin (MβCD) on the evolutionary stages of Schistosoma mansoni in a murine model.

Methods: The development and characterization of the physicochemical properties of the inclusion complex of β-lap in β-lap:MβCD was prepared by solubility and dissolution tests, FTIR, DSC, X-RD and SEM. The mice were infected and subsequently treated with β-lap:MβCD orally with 50 mg/kg/day and 100 mg/kg/day for 5 consecutive days, starting therapy on the 1 (skin schistosomula), 14 (pulmonary schistosomula), 28 (young worms) and 45 (adult worms) days after infection. Control groups were also formed; one infected untreated, treated with MβCD, and the other treated with PZQ.

Results: The loss of the crystalline form of β-lap in the β-lap:MβCD complex obtained by spray drying was proven through physical-chemical characterization analyses. β-lap:MβCD caused reduction in the number of worms of the 33.56%, 35.7%, 35.45% and 36.45%, when the dose was at 50 mg/kg, and 65.00%, 60.34%, 52.72% and 65.01%, in the dose 100 mg/kg; when treatment was started in the 1, 14, 28 and 45 days after infection, respectively. It was also possible to observe a significant reduction in the number of immature eggs and an increase in the number of ripe and dead eggs and, consequently, a reduction in the damage caused by the egg antigens to the host tissue, where we attributed the reduction in the average diameter of the granulomas to the β-lap.

Conclusion: The dissolved content of β-lap:MβCD by spray drying reached almost 100%, serving for future formulations and delineation of the mechanisms of action of β-lap against S. mansoni.