Effects of free and liposomized praziquantel on the surface morphology and motility of Mesocestoides vogae tetrathyridia (syn. M. corti ; Cestoda: Cyclophyllidea) in vitro

Abstract

The effects of in vitro exposure to praziquantel (PZQ), liposomized PZQ (lip.PZQ), and empty liposomes on the surface morphology and motility of Mesocestoides vogae tetrathyridia were investigated using scanning electron microscopy (SEM) and a motility apparatus. Examination of treated larvae showed an effect that was concentration- and time-dependent, involving morphological damage that was similar in character for all of the treated groups. The most marked effects were a flattening and elongation of the larval body accompanied by irregularities in the surface architecture involving the development of tegumental protuberances and depressions. Erosion of the surface microvillous layer occurred only after overnight incubation, being most pronounced after treatment with lip.PZQ. The motility index of treated tetrathyridia corresponded well to the SEM observations. The frequency of contractions was maximal in worms treated with free PZQ at 25 micrograms/ml in both regimens. However, after incubation with lip.PZQ the increase in motility was concentration-dependent and of a greater extent. Empty liposomes and lipid mixtures of the same concentration and composition resulted in increased motility in treated larvae as compared with controls. More extensive tegumental damage and higher motility of larvae occurred after lip.PZQ treatment, perhaps resulting from a synergistic action of the drug and its associated lipid.

Early post-larval development of the endoparasitic platyhelminthMesocestoides corti: Trypsin provokes reversible tegumental damage leading to serum-induced cell proliferation and growth

“…There are some examples of agents that stimulate cestode larval development while reversibly disrupt tegument. That is the case of PKC activators in Schistosoma mansoni (Wiest et al, 1994), praziquantel in M. corti (Britos et al, 2000), and N-lauroyl sarcosinate in Mesocestoides vogae (Hrckova et al, 1998), which concomitantly increased larvae segmentation rates and induced morphological damage on their surfaces. Likewise, bile salts, such as sodium taurocholate, stimulate cestode development (Smyth and Davies, 1974;Esch and Smyth, 1976;Kawamoto et al, 1986;Saldana et al, 2001Saldana et al, , 2003.…”

In vitro taurocholate-induced segmentation and clustering of Mesocestoides vogae (syn. corti) tetrathyridia (Cestoda) – inhibition by cestocidal drugs

“…First, since M. vogae had been found suitable for in vivo drug assays in experimentally infected rodents (Novak 1977;Hrckova et al 1997), we assumed that the addition of a gel to the incubation medium would contribute to reproduce the physicochemical conditions of the peritoneum. In addition, attempts of using tetrathyridia for in vitro drug assays had been hampered by the requirement for high doses and long exposure times for the assessment of toxicity (Hrckova et al 1998). Therefore, we speculated that the inclusion of a developmental factor, sodium taurocholate, while inducing parasite dierentiation, could permit a reduction in drug dose and exposure time.…”

Solid lipid nanoparticle suspension enhanced the therapeutic efficacy of praziquantel against tapeworm

“…18,19 Liposomal formulations have also been prepared to improve the bioavailability, systemic circulation time, and cestocidal activity of PZQ. 20,21 Previous studies demonstrate that solid lipid nanoparticles (SLNs) significantly prolong the systemic circulation time and increased the bioavailability of PZQ. 22,23 The improved bioavailability and systemic circulation time of PZQ could enhance its therapeutic efficacy and reduce dose and administration frequency.…”

“…In addition, the high drug concentration and long drug action time have a synergistic effect to enhance the cestocidal activity of PZQ. 21 Based on the pharmacokinetics of the suspension and cestocidal mechanisms of PZQ, the enhanced cestocidal activity against other cestodes might be anticipated, but further studies need to be done to confirm its broad efficiency to treat tapeworm infections in most mammals.…”

“…Since the cestocidal activity of PZQ is concentration-and time-dependent, 11,21,28 exposure of the tapeworm to higher drug concentrations and/or longer time is essential for adequate treatment of parasite infection. In addition, the high drug concentration and long drug action time have a synergistic effect to enhance the cestocidal activity of PZQ.…”