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Molecules (Basel, Switzerland) Oct 2019Solid lipid nanoparticles (SLNs) can be produced by various methods, but most of them are difficult to scale up. Supercritical fluid (SCF) is an important tool to...
Solid lipid nanoparticles (SLNs) can be produced by various methods, but most of them are difficult to scale up. Supercritical fluid (SCF) is an important tool to produce micro/nanoparticles with a narrow size distribution and high encapsulation efficiency. The aim of this work was to produce cetyl palmitate SLNs using SCF to be loaded with praziquantel (PZQ) as an insoluble model drug. The mean particle size (nm), polydispersity index (PdI), zeta potential, and encapsulation efficiency (EE) were determined on the freshly prepared samples, which were also subject of Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), drug release profile, and in vitro cytotoxicity analyses. PZQ-SLN exhibited a mean size of ~25 nm, PdI ~ 0.5, zeta potential ~-28 mV, and EE 88.37%. The DSC analysis demonstrated that SCF reduced the crystallinity of cetyl palmitate and favored the loading of PZQ into the lipid matrices. No chemical interaction between the PZQ and cetyl palmitate was revealed by FTIR analysis, while the release or PZQ from SLN followed the Weibull model. PZQ-SLN showed low cytotoxicity against fibroblasts cell lines. This study demonstrates that SCF may be a suitable scale-up procedure for the production of SLN, which have shown to be an appropriate carrier for PZQ.
Topics: Carbon Dioxide; Cell Line; Cell Proliferation; Chromatography, Supercritical Fluid; Fibroblasts; Humans; Lipids; Nanoparticles; Palmitates; Praziquantel
PubMed: 31661906
DOI: 10.3390/molecules24213881 -
The Journal of Infectious Diseases Mar 1988Praziquantel undergoes extensive first-pass hepatic biotransformation, but there is little information on its disposition or toxicity when administered to patients with...
Praziquantel undergoes extensive first-pass hepatic biotransformation, but there is little information on its disposition or toxicity when administered to patients with liver disease. To define the influence of liver disease on the pharmacokinetics of praziquantel, we administered it orally to 30 patients with proven Schistosoma japonicum infection whose liver disease was carefully assessed as being severe, moderate, or absent. Both the peak plasma concentration of praziquantel and the bioavailability (measured as the area under the plasma concentration time curve) were significantly greater in the two groups of patients with liver disease (P less than .005), as were the concentrations of the two identified metabolites of praziquantel. Mild side effects were associated with high peak concentrations of praziquantel, but a syndrome of severe abdominal pain followed by bloody diarrhea was not. Our results indicate that the side effects and bioavailability of praziquantel are increased in the presence of liver disease.
Topics: Biological Availability; Female; Humans; Liver Diseases, Parasitic; Male; Praziquantel; Schistosomiasis japonica
PubMed: 3125260
DOI: 10.1093/infdis/157.3.530 -
Cancer Genomics & Proteomics 2021Opisthorchis viverrini (Ov) infection-induced cholangiocarcinoma (CCA) is a major public health problem in northeastern Thailand. Praziquantel was shown to prevent CCA...
BACKGROUND
Opisthorchis viverrini (Ov) infection-induced cholangiocarcinoma (CCA) is a major public health problem in northeastern Thailand. Praziquantel was shown to prevent CCA development in an Ov-infected hamster model; however, the molecular mechanism remains unknown.
MATERIALS AND METHODS
In this study, we used a hamster model with Ov and N-nitrosodimethylamine-induced CCA to study the mechanisms of praziquantel action. The liver tissues from the hamsters with and without praziquantel treatment were analyzed using H nuclear magnetic resonance spectroscopy.
RESULTS
A total of 14 metabolites were found to be significantly different between the two groups. Furthermore, the combination of acetate, inosine and sarcosine was shown to exert an anti-inflammatory effect through interleukin-6 inhibition in a macrophage cell line, suggesting a mechanism by which praziquantel may prevent inflammation caused by Ov, cholangiocyte transformation and further CCA develpoment.
CONCLUSION
These findings might avail the development of a preventive strategy for CCA in high-risk populations.
Topics: Animals; Anthelmintics; Cholangiocarcinoma; Cricetinae; Disease Models, Animal; Humans; Opisthorchis; Praziquantel
PubMed: 33419894
DOI: 10.21873/cgp.20239 -
Experimental Parasitology Aug 1990
Review
Topics: Animals; Immune Tolerance; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni
PubMed: 2115457
DOI: 10.1016/0014-4894(90)90028-b -
American Journal of Physiology. Cell... Feb 2023The anthelmintic drug praziquantel (PZQ) causes contraction of parasitic schistosomes as well as constriction of blood vessels within the mesenteric vasculature of the...
The anthelmintic drug praziquantel (PZQ) causes contraction of parasitic schistosomes as well as constriction of blood vessels within the mesenteric vasculature of the host where the adult blood flukes reside. The contractile action of PZQ on the vasculature is mediated by the activation of host serotonergic 5-HT receptors (5-HTRs). However, the molecular basis for PZQ interaction with these targets and the location of these 5-HT receptors in the vessel wall have not been experimentally defined. Evaluation of a PZQ docking pose within the 5-HTR orthosteric site, using both Ca reporter and bioluminescence resonance energy transfer (BRET) assays, identified residues F340 and F341 (transmembrane helix 6, TM6) as well as L209 (extracellular loop 2) as critical for PZQ-mediated agonist activity. A key determinant of PZQ selectivity for the 5-HT receptor over the 5-HT/ receptors was determined by M218 in transmembrane helix 5 (TM5) of the orthosteric site. Mutation of this residue to valine (M218V), as found in 5-HT and 5-HT, decreased PZQ agonist activity, whereas the reciprocal mutation (V215M) in 5-HT increased PZQ activity. Two-photon imaging in intact mesenteric arterial strips visualized PZQ-evoked Ca transients within the smooth muscle cells of the vessel wall. PZQ also triggered cytoplasmic Ca signals in arterial smooth muscle cells in primary culture that were isolated from mesenteric blood vessels. These data define the molecular basis for PZQ action on 5-HT receptors localized in vascular smooth muscle.
Topics: Praziquantel; Serotonin; Anthelmintics; Arteries
PubMed: 36622066
DOI: 10.1152/ajpcell.00520.2022 -
Lancet (London, England) Feb 1989
Review
Topics: Brain Diseases; Cysticercosis; Evaluation Studies as Topic; Humans; Praziquantel
PubMed: 2563422
DOI: 10.1016/s0140-6736(89)91268-3 -
International Journal of Nanomedicine 2018Lipid nanocapsules (LNCs) have shown potential to increase the bioavailability and efficacy of orally administered drugs. However, their intestinal translocation to...
PURPOSE
Lipid nanocapsules (LNCs) have shown potential to increase the bioavailability and efficacy of orally administered drugs. However, their intestinal translocation to distal target sites and their implication in pharmacokinetic (PK)-pharmacodynamic (PD) relationships are yet to be elucidated. In this study, the effect of LNCs on the PD activity and pharmacokinetics of praziquantel (PZQ), the mainstay of schistosomiasis chemotherapy, was investigated.
MATERIALS AND METHODS
The composition of LNCs was modified to increase PZQ payload and to enhance membrane permeability. PZQ-LNCs were characterized in vitro for colloidal properties, entrapment efficiency (EE%), and drug release. PD activity of the test formulations was assessed in -infected mice 7 days post-oral administration of a single 250 mg/kg oral dose. Pharmacokinetics of the test formulations and their stability in simulated gastrointestinal (GI) fluids were investigated to substantiate in vivo data.
RESULTS
PZQ-LNCs exhibited good pharmaceutical attributes in terms of size (46-62 nm), polydispersity index (0.01-0.08), EE% (>95%), and sustained release profiles. Results indicated significant efficacy enhancement by reduction in worm burden, amelioration of liver pathology, and extensive damage to the fluke suckers and tegument. This was partly explained by PK data determined in rats. In addition, oral targeting of the worms was supported by the stability of PZQ-LNCs in simulated GI fluids and scanning electron microscopy (SEM) visualization of nanostructures on the tegument of worms recovered from mesenteric/hepatic veins. Cytotoxicity data indicated tolerability of PZQ-LNCs.
CONCLUSION
Data obtained provide evidence for the ability of oral LNCs to target distal post-absorption sites, leading to enhanced drug efficacy. From a practical standpoint, PZQ-LNCs could be suggested as a potential tolerable single lower dose oral nanomedicine for more effective PZQ mass chemotherapy.
Topics: Administration, Oral; Animals; Biological Availability; Cell Death; Dose-Response Relationship, Drug; Drug Liberation; Female; Humans; Lipids; Liver; Male; Mice; Nanocapsules; Praziquantel; Rats, Wistar; Schistosoma mansoni; Schistosomiasis mansoni
PubMed: 30122922
DOI: 10.2147/IJN.S167285 -
Annals of Internal Medicine Aug 1983Praziquantel recently has been approved in the United States for use against a broad range of trematodes and cestodes. The drug is highly effective against all...
Praziquantel recently has been approved in the United States for use against a broad range of trematodes and cestodes. The drug is highly effective against all Schistosoma species that infect humans as well as other flukes and tapeworms, including the larval stage of Taenia solium, which causes cysticercosis. In addition, praziquantel is relatively nontoxic, well accepted by patients, and can be given orally in one dose or several doses in a single day. Praziquantel lowers or abolishes the threshold for treating persons with these infections, and, if costs can be contained, may help in the global control of serious systemic helminthic infections.
Topics: Animals; Cestode Infections; Cysticercosis; Dogs; Echinococcosis; Helminthiasis; Humans; Isoquinolines; Praziquantel; Schistosomiasis; Sheep; Swine; Trematode Infections
PubMed: 6881777
DOI: 10.7326/0003-4819-99-2-195 -
PLoS Neglected Tropical Diseases Mar 2021The antihelminthic drug praziquantel has been used as the drug of choice for treating schistosome infection for more than 40 years. Although some epidemiological studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The antihelminthic drug praziquantel has been used as the drug of choice for treating schistosome infection for more than 40 years. Although some epidemiological studies have reported low praziquantel efficacy in cure rate (CR) and/or egg reduction rate (ERR), there is no consistent robust evidence of the development of schistosome resistance to praziquantel (PZQ). There is need to determine factors that lead to variable treatment CR and/or ERR. Therefore, we conducted a systematic review and meta-analysis to review CR and ERR as well as identify their predictors.
METHODOLOGY/PRINCIPAL FINDINGS
In this systematic review and meta-analysis, a literature review was conducted using Biosis Citation Index, Data Citation Index, MEDLINE, and Web of Science Core Collection all of which were provided through Web of Science. Alongside these, EMBASE, and CAB abstracts were searched to identify relevant articles. Random effect meta-regression models were used to identify the factors that influence CR and/or ERR by considering differences in host characteristics and drug dose. In total, 12,127 potential articles were screened and 146 eligible articles (published from 1979 to 2020) were identified and included for the meta-analysis. We found that there has been no significant reduction in CR or ERR over the study period. The results showed more variability in CR, compared with ERR which was more consistent and remained high. The results showed a positive effect of "PZQ treatment dose" with the current recommended dose of 40 mg/kg body weight achieving 57% to 88% CR depending on schistosome species, age of participants, and number of parasitological samples used for diagnosis, and ERR of 95%.
CONCLUSIONS/SIGNIFICANCE
Based on a review of over 40 years of research there is no evidence to support concerns about schistosomes developing resistance to PZQ. These results indicate that PZQ remains effective in treating schistosomiasis.
Topics: Animals; Anthelmintics; Humans; Parasite Egg Count; Praziquantel; Schistosoma; Schistosomiasis; Treatment Outcome
PubMed: 33730095
DOI: 10.1371/journal.pntd.0009189 -
Chemical Biology & Drug Design Aug 2013A series of aromatic ring-modified praziquantel derivatives were prepared and evaluated against juvenile and adult stage of Schistosoma japonicumin. Several analogs...
A series of aromatic ring-modified praziquantel derivatives were prepared and evaluated against juvenile and adult stage of Schistosoma japonicumin. Several analogs comparable in activity to the drug praziquantel have been identified based on in vitro and in vivo japonuicum schistosomes worm viability assay. Structure and activity relationship of these praziquantel aromatic ring-modified compounds was revealed. Specifically, a compound in which a bromine has been introduced in the aromatic ring of praziquantel demonstrated close antischistosomal activity to praziquantel in vivo.
Topics: Animals; Cell Line; Female; Mice; Praziquantel; Rats; Schistosoma japonicum; Schistosomiasis japonica; Schistosomicides
PubMed: 23617439
DOI: 10.1111/cbdd.12153