In vivo treatment of experimental neurocysticercosis with praziquantel nanosuspensions—a metabolic approach

Abstract

Neurocysticercosis is the most common parasitic infection of the nervous system and currently represents a serious public health issue in many regions of Latin America, Asia, and Africa. To date, praziquantel is one of the chosen drugs for the treatment of neurocysticercosis. Its mechanism of action is based on the inhibition of different biochemical pathways within the parasite which contribute to its death. Thus, the aim of this work was to analyze, for the first time, whether the nanoformulations of praziquantel would modify the energetic pathway of Taenia crassiceps cysticerci, after an intracranial inoculation in BALB/c mice. Praziquantel nanosuspensions were formulated with polyvinyl alcohol, poloxamer 188, and poloxamer 407, as stabilizers. These formulations exhibited particle size in a range of 74-285 nm and zeta potential values in a range of - 8.1/- 13.2 depending on the type of stabilizer. Physical stability study at both 4 ± 2 and 25 ± 2 °C indicated that praziquantel (PZQ) nanoparticles were stable in terms of solubility and particle size after 120-day storage. In vivo studies demonstrated that those nanosystems were able to produce significant modifications on the concentrations of oxaloacetate, citrate, pyruvate, alpha-ketoglutarate, malate, succinate, lactate, beta-hydroxybutyrate, fumarate, and propionate involved in the metabolism of Taenia crassiceps cysticerci. Therefore, these nanoformulations may be considered as a promising tool to deliver praziquantel to the brain for the effective management of neurocysticercosis.

Chitosan-based nanodelivery systems applied to the development of novel triclabendazole formulations

“…Several strategies have been used to improve the aqueous solubility and further bioavailability of drugs including the development of solid dispersions, complexation with cyclodextrins and polymeric microencapsulation [11,12,13,14,15]. Lately, reduction of the particle size from micro- to nanometer range has been recognized as a promising approach to improve the apparent saturation solubility, dissolution rate and oral bioavailability of hydrophobic molecules (BCS Class II/IV drugs) [16,17]. When compared with microparticulate delivery devices, particles of small size (<1 μ m) are likely to accumulate in the site of action, increase the concentration at the target site and hence, improve the therapeutic efficacy.…”

The Effect of Different Formulations of Praziquantel in Reducing Worms in the Prepatent Period of Schistosomiasis in Murine Models

“…The present study also evaluated the PZQ-NANO therapy to offer an alternative for the treatment of Schistosomiasis mansoni. Nanoencapsulated pharmaceutical formulations represent an increasingly used drug delivery system, mainly for the treatment of some neglected diseases (39)(40)(41)(42)(43)(44)(45). Studies have pointed out that nanoformulations improve drug stability and bioavailability and direct it to the target zone, as well as optimize therapy and reduce adverse effects (41,42).…”

Partial inhibition of the main energetic pathways and its metabolic consequences after in vivo treatment with benzimidazole derivatives in experimental neurocysticercosis

“…This period of time was chosen due to the half-life of ABZ which is approximately 8–12 h, ensuring the metabolic effect of the drug on the parasite. The cysticerci were carefully removed, washed with physiologic solution (NaCl 0.9%) in order to remove host cells or other interferents, and then frozen in liquid nitrogen and stored in −20 °C freezer for posterior biochemical analysis (Leandro et al ., 2014; Silva et al ., 2018; Lima et al ., 2019).…”

“…One of the validated experimental models used for cysticercosis studies is with the intraperitoneal and intracranial inoculation of Taenia crassiceps cysticerci in mice, reproducing the cysticercosis host-parasite interaction (Cardona and Teale, 2002; Matos-Silva et al ., 2012; Leandro et al ., 2014; Lima et al ., 2019). The T. crassiceps experimental NCC model has been used as to contribute in the clarifying of the biochemical impact of different drugs in the metabolic pathways of the parasite (Leandro et al ., 2014; Silva et al ., 2018; Lima et al ., 2019).…”

“…Such studies contribute to the development of new active compounds and improvement of the current anthelminthic drugs, i.e. development of nanosuspensions increasing the drug`s absorption by the parasitic cell as well as decreasing dosages and side-effects (Vinaud et al ., 2007; Picanço et al ., 2017; Silva et al ., 2018; Lima et al ., 2019).…”