الفهرس 
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Abstract
Trichinellosis is a zoonotic parasitic disease caused by T. spiralis. It is considered a
health problem as it affects humans in many countries worldwide. T. spiralis is a viviparous
nematode characterized by completing its life cycle in a single host. Adult worms spend the
majority of their life in the intestines of their hosts. They produce larvae that invade the
hosts’ muscles. The larvae are encapsulated as a small cystic structures within a muscle cell
of the infected hosts. Human infection take place by eating inappropriately cooked pork
infected by the encysted larvae.
Trichinellosis mostly affects muscles, however it can potentially result in catastrophic
consequences including myocarditis and encephalitis. The effectiveness of chemotherapy
with albendazole or mebendazole, for example, is mostly determined by the timing of
administration; treatment only at the earliest stage of infection gives good results. Several
studies have sought to identify new alternative drugs to treat trichinellosis.
The present study aimed to compare the effectiveness of albendazole and the anti-
diabetic medication metformin loaded on chitosan nanoparticles in treating mice with
various stages of T. spiralis infection. Total of 160 parasite free mice were included in the
present study; 40 mice were used as control groups. 140 mice were orally infected with
approximately 0.5 ml PBS containing 200- 300 T. spiralis ML per each mouse by using
esophageal syringe. All drugs were administered according to the corresponding design of
groups and sub groups as follows:
Albendazole was used, as the gold standard drug for treatment in a dose of 50 mg/kg
orally for 5 successive days starting from the 1st day of infection for the enteral phase
and from the 30th d.p.i for the parenteral phase.
Albendazole loaded Chitosan nanoparticles were used in a dose of 50 mg/kg orally
for 5 successive days starting from the 1st day of infection for the enteral phase and
from the 30th d.p.i for the parenteral phase.
Metformin loaded Chitosan Nanoparticles were used in a dose of 50 mg/kg orally for
5 successive days starting from the 1st day of infection for the enteral phase and from
the 30th d.p.i for the parenteral phase.
Albendazole and metformin loaded chitosan nanoparticles were used in a full dose of
50 mg/kg of each prepared drug orally for 5 successive days starting from the 1st day
of infection for the enteral phase and from the 30th d.p.i for the parenteral phase.
Albendazole and metformin were used in a full dose of 50 mg/kg orally for 5
successive days starting from the 1st day of infection for the enteral phase and from the
30th d.p.i for the parenteral phase.
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The dose was adjusted that each mouse received the calculated dose of the chosen drug
according to its body weight in 0.5 ml. Regarding the effect of the studied drugs on the
intestinal phase, results of the present study showed that all subgroups showed a statistically
significant difference compared to control non-treated group (P< 0.001). The highest
reduction of the total adult count was achieved by Cs NPs loaded with ABZ and MET
(7.3±1.6), followed by the infected group that was treated with Cs NPs loaded with a full
dose of ABZ (14.3±3.4), then the group treated with combined ABZ and MET (23.3±4.6),
then the group treated with ABZ alone (32.7±6.4) and the infected group that was treated
with Cs NPs loaded with MET (53.2±6.3). Finally, the group treated with MET alone
showed the lowest reduction in count (77.2±8.4).
As regards the effect of the studied drugs on encysted muscle larvae, all groups
showed a statistically significant difference compared to control non-treated group (P<
0.001). The highest reduction of the muscle larvae count was achieved by Cs NPs loaded
with a full dose of ABZ and MET (100.8±9.1), followed by the infected group that was
treated with Cs NPs loaded with a full dose of ABZ (156.8±7.4), then the group treated with
combined ABZ and MET (243.0±44.3), then the group treated with ABZ alone (298.3±25.1)
and the infected group that was treated with Cs NPs loaded with MET (469.5±36.6). Finally,
the group treated with MET alone showed the lowest reduction in count (703.8±17.2).
Concerning the histopathological changes in the intestinal phase of the infection,
examination of the infected control revealed severe inflammation, dense inflammatory
infiltrate in lamina propria, reactive lymphoid follicles, edema, destruction of intestinal villi
and ulceration. Marked improvement of inflammation was observed in group treated with
Cs NPs loaded ABZ, Cs NPs loaded with combination of Albendazole and Metformin,
Albendazole, Metformin and the combination of full doses of both ABZ and MET. The
intestines showed mild mucosal chronic mononuclear inflammatory infiltrate. While the
infected mice that were treated with Cs NPs loaded with MET showed multiple coiled adult
worms in the lumen with moderate stromal inflammatory infiltrate with eosinophils.
Concerning the histopathological changes in the parenteral phase of the infection,
examination of the skeletal muscles of the infected control revealed multiple nurse cells
entangling degenerating larvae surrounded by moderate chronic mononuclear inflammatory
infiltrate with adjacent reactive LN. Marked improvement was observed in the group treated
with Cs NPs loaded with ABZ. The muscles were free of infection. Similar results were
observed in the infected mice that were treated with a combination of Cs NPs loaded with
ABZ and MET and the infected mice treated with a combination of ABZ and MET. The
infected mice that were treated with Cs NPs loaded with MET and those treated with MET
showed several nurse cells entangling the encysted larvae with surrounding mild to moderate
chronic mononuclear inflammatory infiltrate with adjacent reactive LN. In the infected mice
that were treated with ABZ, the skeletal muscle fibres showed multiple foci of chronic
mononuclear inflammatory infiltrate with no evident nurse cells.
SEM examination of the tegument of the control untreated T. spiralis ML groups
showed the typical coiling behaviour and the characteristic pattern of tegument. Also, T.
spiralis adult worms of the control group showed normal morphology with preserved
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tegument and normal appearance of the hypodermal gland opening. SEM examination of the
tegument of T. spiralis adults and ML recovered from all treated groups treated with the
studied drugs loaded on Cs NPs showed destruction with multiple degenerative changes. The
destruction was more obvious in the group treated with combined ABZ and MET loaded on
Cs NPs . The degenerative changes were in the form of the appearance of multiple masses
and sloughing of the tegument in some areas