Preclinical Evaluations of Modified Rice Hydrogel for Topical Ophthalmic Drug Delivery of Praziquantel on Avian Philophalmiasis

Abstract

The present study aims to evaluate the efficacy of a novel drug delivery system of the modified rice hydrogel containing praziquantel (PZQ) against Philophthalmus gralli isolated from ostrich eyes and determine the toxicity of the preparation on chicken eye model. The parasiticidal activity of PZQ (0, 1, 10, and 100 µg/mL) was tested on P. gralli. The ophthalmic antiparasitic hydrogel was formulated with appropriate amount of PZQ and chemically modified rice gel. The parasitic morphology after exposure with the preparation was examined under scanning electron microscope (SEM). The anthelminthic efficacy of the preparation on motility and mortality of parasites was performed by visual inspection and vital dye staining. The ocular irritation of the preparation was evaluated for 21 days using standard avian model followed by OECD 405. The results demonstrated that the parasiticidal activity of PZQ against P. gralli appears to be in a concentration- and time-dependent manner. In addition, the concentration of PZQ 10 µg/mL (Chi squared test, p = 0.003) and exposure time for 24 h (log-rank test, p = 0.0004) is sufficient to kill parasites, when statistically compared to negative control group. Rice hydrogel containing a lethal concentration of 10 µg/mL PZQ was successfully prepared. The preparation illustrated good parasitic killing and motile inhibiting effect on P. gralli compared with PZQ 10 µg/mL and its control (p < 0.05). An appearance under SEM of non-viable parasite after being incubated with the preparation, showing parasitic deformity, was observed comparing with the viable parasite in 0.9% normal saline solution (NSS). Moreover, no irritation of chicken eyes was also observed. Our results contribute to understanding the efficacy and the safety of the rice hydrogel of PZQ which have a predictive value for controlling P. gralli on the animal eyes. However, the pharmacological application needs to be further investigated for the best possible therapeutic approach.

Recent large-scale philophthalmosis outbreak in Portugal: inefficacy of common antihelminthic agents

“…Similarly, we were unable to confirm the promising in vitro data reported for praziquantel in the treatment of the closely related P. gralli [ 18 ]. In our in vivo trial, we did not observe any effect of praziquantel when administered in combination with milbemycin (Table 2 ).…”

“…In our in vivo trial, we did not observe any effect of praziquantel when administered in combination with milbemycin (Table 2 ). Praziquantel is toxic to Philophthalmus in vitro [ 18 ]. However, in a previous study it was found to be ineffective when used for 3 consecutive days in multitherapy with pyrantel and fenbendazole in vivo [ 7 ].…”

“…have also been reported to cause ocular swelling, conjunctivitis, persistent lacrimation and ocular purulent discharge [ 16 , 17 ]. Praziquantel effectively kills P. gralli in vitro when administered at 10 μg ml -1 for 24 h [ 18 ]. This anti-worm medication has also been used in vivo to treat captive rheas [ 19 ].…”

In vitro evaluation of the antihelminthic activity of Praziquantel, Flubendazole and some plant extracts against the adult eye fluke (Philophthalamus palpebrarum) transmitted by the freshwater snail Melanoides tuberculata.

“…Similar results have been previously reported by many researchers when testing the in vitro effect, eg. PZQ (Kato et al, 2013;Prompetch et al, 2021), seeds of J. curcas (Kandil et al, 2018), seeds of M. oleifera (Eguale & Giday, 2009) on Schistosoma mansoni, Philophthalmus gralli, Haemonchus contortus, Fasciola hepatica, respectively.…”

“…Also, has been found Venezuela (Diaz et al, 2002), Brazil (Verocai et al, 2009) and in Zimbabwe (Mukaratirwa et al, 2005) In general a variety of mammals, including humans, occasionally serve as the intermediate as well as the definitive hosts for the genus Philophathalamus. Moreover, the zoonotic philophthalmiasis in human cases has been also documented in various parts of the world (Sapp et al, 2019 andPrompetch et al, 2021). Lang et al, 1993;Kanev et al, 1993 &Kanev, 1995 reported cases of human infection and conjunctivitis in eyes due to infection with P. palpebrarum; P. lucipetus and P. lachrymosus, respectively.…”