PZQ is a class II compound (high permeability, low solubility) and is highly lipophilic. The failure to achieve complete cures in PZQ-treated populations may be linked to the insufficient long-lasting effect of PZQ and its low bioavailability, which is attributed to the hydrophobic nature of the drug. Since PZQ does not show a 100% cure rate, the surviving worms might develop resistance quickly hence, this resistance might be passed on to the next generations of Schistosoma. Although mass administration campaigns of PZQ as well as preventive measures through chemotherapy have shown a significant impact on schistosomiasis, the efficacy concerns are debatable in addition to the possible development of drug resistance. Praziquantel (PZQ) remains the only effective frontline drug to treat the parasite and is currently characterized by its exclusive and extensive use as an important antischistosomal drug.
Despite this considerable disease burden, at present, there is no effective vaccine, the intermediate host is not always easily defeated and chemotherapy remains the primary approach for disease control. Over 200 million individuals are infected worldwide, and schistosomiasis is within the top ten diseases for years lived with disability in sub-Saharan countries. Schistosomiasis, a neglected tropical parasitic disease, is endemic in more than 75 countries. SLN-PZQ demonstrated enhanced PZQ bioavailability and antischistosomal efficacy with a safe profile despite the prolonged residence in the systemic circulation. The ED 95 of SLN-PZQ was 5.29-fold lower than that of M-PZQ, with a significantly higher reduction in both the hepatic and intestinal tissue egg loads of all treated groups and almost complete disappearance of immature deposited eggs (clearly evident at the low dose levels). This effect was especially evident at the lower dose levels. Compared to M-PZQ, SLN-PZQ revealed superior antischistosomal activity coupled with enhanced bioavailability in all treated groups where higher percentages of worm reduction were recorded with all dosages tested. Additionally, enhanced absorption with extended residence time was recorded for SLN-PZQ. mansoni-infected mice, SLN-PZQ was detectable in serum at 24 h, while M-PZQ completely vanished 8 h post-treatment. The AUC 0–24 for SLN-PZQ in normal and Schistosoma mansoni-infected groups was almost nine- and eight-fold higher, respectively, than that for M-PZQ in corresponding groups.
ResultsĬompared to market PZQ (M-PZQ), SLN-PZQ was more bioavailable, as denoted by higher serum concentrations in both normal and infected mice where elevated K a, AUC 0–24, C max, and t 1/2e with a decrease in k el were demonstrated.
A simple, cost-effective method was used to prepare SLN-PZQ. This work aimed to improve the therapeutic outcome of the only available antischistosomal drug worldwide, praziquantel (PZQ), by incorporating it into a novel carrier, “solid lipid nanoparticles (SLNs)”, to enhance its solubility, bioavailability and efficacy. Schistosomiasis is responsible for a considerable global disease burden.
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