Content uploaded by Alireza Sazmand
Author content
All content in this area was uploaded by Alireza Sazmand on Apr 10, 2025
Content may be subject to copyright.
hp://bdvets.org/javar/ 1122
Marchenko et al. / J. Adv. Vet. Anim. Res., 11(4): 1122–1129, December 2024
JOURNALOFADVANCEDVETERINARYANDANIMALRESEARCH
ISSN2311-7710(Electronic)
hp://doi.org/10.5455/javar.2024.k863December 2024
A periodical of the Network for the Veterinarians of Bangladesh (BDvetNET) VOL11,NO.4,PAGES1122–1129
ORIGINALARTICLE
Ecacy of niclosamide and ivermecn suspension preparaons in sheep parasitoses
VictorA.Marchenko1,YuryA.Vasilenko1,IvanV.Biryukov1,MaratS.Khalikov2,
SalavatS.Khalikov2,AlirezaSazmand3
1Gorno-AltayResearchInstuteofAgriculture(branch)ofNaonalResearch,TomskStateUniversity,Barnaul,Russia
2A.N.NesmeyanovInstuteofOrganoelementCompounds,RussianAcademyofScience(RAS),Moscow,Russia
3DepartmentofPathobiology,FacultyofVeterinaryMedicine,Bu-AliSinaUniversity,Hamedan,Iran
Contact SalavatS.Khalikov khalikov_ss@ineos.ac.ru A.N.NesmeyanovInstuteofOrganoelementCompounds,RussianAcademyofScience(RAS),
Moscow,Russia.
AlirezaSazmand alireza.sazand@basu.ac.ir DepartmentofPathobiology,FacultyofVeterinaryMedicine,Bu-AliSinaUniversity,Hamedan,Iran.
How to cite this arcle: MarchenkoVA,VasilenkoYA,BiryukovIV,KhalikovMS,KhalikovSS,SazmandA.Ecacyofniclosamideandivermecnsuspensionpreparaons
insheepparasitoses.JAdvVetAnimRes2024;11(4):1122–1129.
ABSTRACT
Objecve:Thisstudyaimedtoexaminetheeciencyofnewlyformulateddrugsbasedonmech-
anochemicalmodicaonoftwowidelyusedanthelmincsubstancesinsuspensionformulaons
againstthemainclassesofhelminthsandparasicarthropods.
Materials and Methods:Solid-pha se co-grindingof two substances, i.e., ivermecn (IM) and
niclosamide(NS),withlicoriceextractandsodiumsuccinatewasperformedinliquid-phasepro-
cessingtoobtain suspension formulaons.Drug preparaonswereadministered tothe sheep
ofthe experimentalgroups(5experimentalgroups of8heads)withdierentconcentraonsof
acvesubstances,i.e.,3.0,5.0,and10.0mg/kgofbodyweight(BW)NSand0.2-mg /kgBWIM.
Aqueoussuspensionsoftheoriginalsubstancesindosagesof0.2-mg /kgBWIM,10.0-mg/kgNS,
andplacebowereincludedascontrols.Ecacyoftheformulaonsagainstgastrointesnalstron-
gyles,Trichurisspp.,Monieziaspp.,andnasalbotlarvae(Oestrus ovis)wasassessedinnaturally
infectedsheepbythenumberofsurvivingadult parasitespost-treatmentinthegastrointesnal
tract,nasalpassages,andsinuses.
Results:Formulatedsuspensionsshowedanincreasedsolubilityof5.5–13.1mescomparedto
theoriginalsubstances.TreatmentofsheepwiththeSusIN-10drugcontaining0.2-mg/kgBWIM
and 10.0-mg/kg NS showed 100% eciency against gastrointesnal strongyles, Moniezia, and
nasal bot larvae. Formulaons containing0.2-mg /kg BW IM and 3.0- and 0.5-mg/kg NS could
eliminatealloftheTrichurisworms.AdministraonoforiginalsubstancesofIMandNSwithrec-
ommendeddosagesdidnotresultintheadultparasites’completeeliminaon.
Conclusion: Modicaon of the anthelminc substances through mechanochemical methods
madeit possibleto createformulaonswith atargetedspectrumofacon,signicantlyhigher
watersolubility,andopmalparasicidalacvity.
ARTICLE HISTORY
ReceivedMarch17,2024
RevisedNovember01,2024
AcceptedDecember14,2024
PublishedDecember29,2024
KEYWORDS
Drugtesng;helminth;
mechanochemistry;ovine;
parasicidalacvity
Introducon
Parasitic diseases are major constraints in sheep farming
worldwide. Considering the prevalence of mixed infections
with different parasite taxa, the administration of com-
plex antiparasitic preparations with a wide spectrum of
activity is necessary. The use of multi-taxa-affecting drugs
based on different substances makes it possible to affect
the entire spectrum of parasites with a reduced volume of
drug use and reduced frequency of animals’ manipulations
[1]. It has been shown that most antiparasitic substances
are organic compounds poorly soluble in water [2]; hence,
to achieve the desired therapeutic effect, it is always nec-
substance in the preparation, which leads to an increase
in the product cost and, importantly, the release of higher
amounts of the unchanged drugs and their metabolites
into the environment [3].
To improve the solubility of antiparasitic substances
and their pharmacokinetic properties, and also increase
the effectiveness of various physicochemical meth-
ods, such as reducing the size of crystalline particles to
©Theauthors.ThisisanOpenAccess
arcledistributedunderthetermsof
theCreaveCommonsAribuon4.0
License(hp://creavecommons.org/
licenses/by/4.0)
hp://bdvets.org/javar/ 1123
Marchenko et al. / J. Adv. Vet. Anim. Res., 11(4): 1122–1129, December 2024
nano-size by grinding and obtaining dosage forms such as
nanosuspensions, microcapsules, etc. [4], preparing solid
lipid nanoparticles and nanocapsules [5,6], designing poly-
meric forms of drugs in the form of micelles [7], and form-
ing solid dispersions (SDs) of medicinal substances [8] are
used. The compositions obtained with these methods will
disadvantages of low bioavailability, poor cell permeabil-
-
parasitic drugs from the body [9].
-
zole (FBZ)—a broad-spectrum dewormer that is used to
treat many intestinal parasites—by joint grinding with
licorice extract (LE) and sodium dioctyl sulfosuccinate
-
tions [10], and we believe that the solubility of niclosamide
(NS)—an anthelmintic medication used to treat tapeworm
infections—will increase the same way. Licorice is a plant
containing 25% glycyrrhizic acid (GA) and is known to
have a wide range of biological activities, which helps to
improve the membrane conductivity of medicinal sub-
stances [11]. Na-DSS, on the other hand, is used as an
antihypoxic and antioxidant effect [12].
Internal parasites complex of sheep in the farms of
the region is represented by all the main taxa with fairly
constant infection rates: nematodes (60%–80%), trem-
(65%–75%). In particular, 84%–94% of the sheep raised
in this territory (Ust-Koksinsky region) were previously
reported to be infected by Oestrus ovis larvae in their nasal
passages and sinuses [13]. Therefore, it is advisable to con-
duct research not only on the synthesis and search for new
anthelmintic substances, which is an extremely expensive
and the production of complex preparations from several
substances with different mechanisms of action.
The aim of this study was to obtain complex therapeu-
tic drugs based on substances of ivermectin (IM) and NS
and test their parasiticidal activity against common para-
sitic infections of sheep, i.e., nematodes and cestodes of the
O. ovis
(Linnaeus 1758) in the Altai Mountains.
of newly formulated drugs based on the mechanochemical
IM and NS, in suspension formulations against the main
classes of helminths and parasitic arthropods.
Materials and Methods
Ethical approval
This study was approved by the State order of the Federal
and the FASCA Bioethics Commission, order No. 210, dated
October 12, 2022. All applicable international, national,
and/or institutional guidelines for the care and use of ani-
mals were followed.
Materials
IM substance was purchased from Shandong Qilu King-
Phar Pharmaceutical Co. Ltd. (Shandong, China). NS
substance was obtained from Ghangzhou Yabang-Qh
powder of dark brown color with a content of 25% GA—
was taken from Visterra Ltd. (Altay, Russia). Na-DSS was
purchased from Acras Organics (New Jersey, USA). Sodium
salt of carboxymethyl cellulose (Na-CMC = blanose) was
The target composions in the form of aqueous suspen-
sions were obtained as follows
First, the solid-phase mechanochemical treatment of the
IM and NS substances was carried out with LE (stage 1)
and further addition of Na-DSS (stage 2) under the con-
ditions described earlier [16]. The obtained SD composi-
tions IM:LE (1:9) and NS:LE (1:9), which are light brown
powders with increased solubility of substances (Table 1),
were subjected to further mechanical processing by add-
ing the appropriate amount of Na-DSS to obtain the com-
positions IM:LE:Na-DSS (1.0:8.8:0.2) and NS:LE:Na-DSS
(1.0:8.8:0.2). The products of mechanical processing were
SD, which had an increased solubility (Table 1). Obtained
SD were used to obtain the corresponding single suspen-
sion formulations of IM (SusI), containing 2.9% IM, and
NS (SusN), containing 3.4% NS. Afterward, complex sus-
pension formulations were prepared from single suspen-
sions previously obtained, taking into account the required
dosage of drugs. Three suspensions with the abbreviation
Suspension of Ivermectin and Niclosamide (SusIN) were
achieved, i.e., SusIN-3 (at the rate of 0.23 mg of IM and 3.51
mg of NS in 1 ml of suspension), SusIN-5 (at the rate of 0.23
mg of IM and 5.85 mg of NS in 1 ml of suspension), and
SusIN-10 (at the rate of 0.23 mg of IM and 11.7 mg of NS in
1 ml of suspension).
To administer as controls, suspension samples of the
initial substances (without LE and Na-DSS) were prepared
by suspending IM and NS separately using a rotary stirrer
in a 0.2% aqueous polymeric solution of Na-CMC at the
rate of IM: 0.23 mg and NS: 11.7 mg in 1 ml of suspension.
hp://bdvets.org/javar/ 1124
Marchenko et al. / J. Adv. Vet. Anim. Res., 11(4): 1122–1129, December 2024
Solubility study
The solubility of the resulting SD was determined by the
of the SD in water for 3 h by high-performance liquid chro-
matography on an Agilent 1,200 chromatograph with a
Zorbax Eclipse XDB-C18 column, 4.6 × 50 mm (Agilent
Technologies, CA, USA); column temperature +30°C;
diode-matrix detector. An acetonitrile acetate buffer pH
min, and the sample volume was 5 µl [14]. The analysis
error was ±3%.
Determinaon of parcle sizes in soluons of the suspen-
sion formulaons
Dynamic light scattering (DLS) technology [15] was used
to estimate the average particle size and polydisper-
sity index of obtained suspension formulations by the
Photocor Complex Instrument (Photocor, Moscow) at
25°C. The compositions were dissolved in distilled water
before measurement. The results were obtained by mea-
suring three times and taking the average value.
Study animals
Previous studies in the Altai Mountains reported the
maximum infection of helminths and O. ovis larvae to
occur between September and October, during which
antiparasitic treatments of sheep are recommended [1].
Henceforth, we chose this optimal period for assessing the
effectiveness of the drugs.
A randomized and placebo-controlled study was car-
agricultural production cooperative “Amur” in the Ust-
Koksinsky district of the Altai Republic in accordance with
the Guidelines for the Experimental (Preclinical) Study of
New Pharmacological Substances [16] and the European
Convention for the Protection of Vertebrate Animals Used
[17].
During the experiment, the sheep did not graze on the
pasture; they were kept indoors and fed according to the
norms and rations for feeding livestock [18].
Fifty sheep of the Gorno-Altai breed aged 16–18
months weighing 35–40 kg were included. Three days
before the experiment, individual rectal fecal samples from
20 randomly selected animals were examined according
to Kotelnikov–Khrenov’s method using a VIGIS counting
chamber. Results showed infection with gastrointestinal
strongyles in 55.0% (mean EPG = 75.2), Trichuris in 30.0%
(mean EPG = 32.5), and Moniezia in 20.0% (mean EPG =
41.3) of animals. The relatively low infection rate is most
likely due to the grazing of animals in the summer on high
alpine pastures. Five experimental groups of 8 sheep and
1 control group of 10 sheep with close infection rates were
randomly formed.
Treatments of animals
Suspension preparations (SusIN) were fed to the sheep
of the experimental groups at a dosage according to the
NS—3.0, 5.0, and 10.0 mg/kg body weight (BW) and IM
at 0.2-mg/kg BW. Aqueous suspensions of the original
substances were used in dosages of IM—0.2-mg/kg BW,
NS—10.0-mg/kg BW, and placebo (control group) in the
form of 0.2% blanose were also fed to animals with the
same volume as SusINs.
For assessment of possible side effects, clinical param-
eters, such as temperature, pulse rate, respiration rate,
rumen movement, and behavior, were checked before and
on days 1, 3, and 5 post-treatment in the morning before
feeding according to the method of veterinary clinical lab-
oratory diagnostics [19].
Study of the parasical acvity of drugs
days post-treatment after slaughter at a local meat pro-
cessing plant by naked-eye examination of the abomasum,
small, and large intestines. At the same time, the mucous
membranes of the nasal and adnexal cavities of the sheep
proportion of infected animals, arithmetic and geometric
recovered parasites were recorded [20].
Table 1. SolubilityinthewaterofSDsamplesbasedonIMandNS.
Sample, its composion, preparaon condions, and content of IM and NS Water solubility
Absolute (mg/l) Increased (mes)
IM(inialsubstance),97.5%IM 4.0 −
SDoftheIM:LE(1:9)aer3hofmechanicaltreatment;10.0%IM 21.9 5.5
SDoftheIM:LE:Na-DSS(1.0:8.8:0.2)aer3hofmechanochemicaltreatment;10.0%IM 52.4 13.1
NS(inialsubstance),98.0%NS 5.0 −
SDoftheNS:LE(1:9)aer3hofmechanochemicaltreatment;10.0%NS 6.5 1.5
SDoftheNS:LE:Na-DSS(1.0:8.8:0.2)aer3hofmechanochemicaltreatment10.0%NS 31.3 6.3
hp://bdvets.org/javar/ 1125
Marchenko et al. / J. Adv. Vet. Anim. Res., 11(4): 1122–1129, December 2024
Parasiticidal activity evaluation based on the calculation
of two effectiveness indicators as used previously [1]: IE %
= decrease in the arithmetic mean number of parasites of
the experimental groups in relation to the control and EF
% = decrease in the geometric mean number of parasites
of the experimental groups in relation to the control.
To compare the differences between the experimental
and control groups of animals, a t-test was used in SAS/
Stat software (SAS version No. 9, System for Windows).
p
differences. The use of two methods for calculating the
effectiveness (EF and IE) allows you to more fully judge the
parasiticidal activity of drugs.
Results
Analysis of the solubility of SD
-
tions containing IM and NS increased 5.5 and 1.5 times
after co-grinding of LE with the original substance.
Additionally, after the addition of Na-DSS to the SDs, the
solubilities increased by a factor of 13.1 and 6.3. Hence, two
compositions, IM:LE:Na-DSS (1:8.8:0.2) and NS:LE:Na-DSS
(1:8.8:0.2), were chosen for biological testing (Table 1).
Preparaon of suspension formulaons
Samples of aqueous suspensions of SusIN were prepared
from previously obtained SD by suspending them with a
rotary mixer and loading the calculated amounts of these
SDs. The corresponding SusIN suspensions were obtained
and presented in the calculated volume per kg of sheep
BW as follows: i) 0.83 ml of SusIN-3 suspension contained
0.2-mg IM and 3.0-mg NS; ii) 0.83 ml of SusIN-5 suspen-
sion contained 0.2-mg IM and 5.0-mg NS; and iii) 0.83 ml
of SusIN-10 suspension contained 0.2-mg IM and 10.0-mg
NS.
The particle size of the resulting suspensions was deter-
mined as 225 ± 40 nm according to the DLS technology
[15] using Photocor Compact-Z (Fotokor, Moscow, Russia).
The size distribution of the particles in the aqueous sus-
pension of SusIN-10 is shown in Figure 1.
According to DLS results, a narrow monodisperse size
distribution (225 ± 40 nm) was observed for nanosuspen-
sion particles based on LE and Na-DSS. It can be assumed
that these are the micelles of GA, the content of which in LE
is about 25%. This is consistent with previous studies on
the sizes of GA micelles [21].
Clinical data
Examined health parameters of the animals remained
within the physiological range.
Parasitological data
Parasiticidal activity of drugs in the case of the gastro-
intestinal tract strongyles is shown in Table 2. When
examining the gastrointestinal tracts of sheep in the experi-
mental and control groups, the adult stages of Teladorsagia,
Trichostrongylus, Nematodirus, Oesophagostomum, and
Chabertia -
viving adult parasites in the experimental groups, calcu-
Figure 1. DLS measurement of particle size of aqueous suspension of SusIN-10.
hp://bdvets.org/javar/ 1126
Marchenko et al. / J. Adv. Vet. Anim. Res., 11(4): 1122–1129, December 2024
was not feasible. Therefore, the total number of infected
animals and the total count of all adult helminths of the
In experimental groups 2 (SusIN-3) and 4 (SusIN-10), all
performance indicators were 100%. The effectiveness of
the SusIN-5 suspension (group 3) was also quite high, as
an IE% of 97.4 and an Ef% of 92.3 were recorded. Although
the original form of IM (group 5) showed effectiveness, the
3, SusIN-5, and SusIN-10 groups. As expected, administra-
tion of the original substance of NS (group 6) at a dosage of
10-mg/kg BW was not effective.
Inspection of the large intestines revealed that in
experimental groups 2 (SusIN-3) and 3 (SusIN-5), all per-
formance indicators were 100%. The effectiveness of the
SusIN-10 suspension (group 4) was also good, i.e., both
quite IE and Ef >91%, but unchanged IM (group 5) at the
-
cacy (IE = 82.0% and Ef = 60.4%). Suspension of substance
NS (group 6), at a dosage of 10-mg/kg BW with trichurosis,
did not show parasiticidal activity (Table 3).
With regard to the cestocidal effect of the formulations,
unchanged NS with a dose of 10 mg/kg BW, also SusIN-3
SusIN-10, however, proved to be effective in the removal of
all adult tapeworms (Table 4).
When examining the mucous membranes of the nasal
passages, ethmoid bones, and adnexal cavities of the sheep
heads, 1st and 2nd instar larvae of O. ovis were found in
all groups except animals receiving SusIN-5 and SusIN-10
original substance of IM was also acceptable (Table 5).
Table 2. Eciencyofsamplesofsuspensionsingastrointesnalstrongylosisofsheep.
Experiment number/
group of animals # in group Test product Dose (mg of acve substance/
kg BW)
# remaining
parasitesaIEc % Efd % p-valuee
1/Control 10 Placebo 0 19.1±6.8
1.3±0.17 ---
1/Treatment 8 SusIN-3 ModiedIM0.2
ModiedNS3.0
0
0100 100 NAf
2/Treatment 8 SusIN-5 ModiedIM0.2
ModiedNS5.0
0.5±0.27
0.1±0.08 97.4 92.3 <0.01
3/Treatment 8 SusIN-10 ModiedIM0.2
ModiedNS10.0
0
0100 100 NA
4/Treatment 8 SusIM OriginalsubstanceIM0.2 1.3±0.5
0.34±0.13 93.2 73.9 <0.01
5/Treatment 8 SusNS OriginalsubstanceNS10.0 17.8±5.6
1.1±0.15
6.8 15.4 >0.05
aNumberofparasites—thenumeratoristhearithmecmeanandthedenominatoristhegeometricmeannumberofparasites;bEE:extensiveeciency,the
proporonofanimalsfreedfromparasitesinrelaontothecontrol;cIE:intensityeciency,decreaseintheaverage(arithmec)indicatorofthenumberof
eggsinrelaontocontrol;dEf:decreaseinthegeometricmeanvaluesofthenumberofhelmintheggsoftheexperimentalgroupsinrelaontothecontrol;e
stascallysignicantatp≤0.05whengeometricmeanswerecomparedtoplacebo;fNA:stascalanalysiswasnotperformed.
Table 3. Ecacyofsuspensionsamplesinsheeptrichurosis.
Experiment number/
group of animals # in group Test product Dose (mg of acve substance/
kg BW)
# remaining
parasitesaIEc % Efd % p-valuee
1/Control 10 Placebo 0 6.2±2.8
1.16±0.09 ---
1/Treatment 8 SusIN-3 ModiedIM0.2
ModiedNS3.0
0
0100 100 NAf
2/Treatment 8 SusIN-5 ModiedIM0.2
ModiedNS5.0
0
0100 100 NA
3/Treatment 8 SusIN-10 ModiedIM0.2
ModiedNS10.0
0.37±0.26
0.1±0.1 94.1 91.4 <0.01
4/Treatment 8 SusIM OriginalsubstanceIM0.2 1.12±0.6
0.46±0.09 82.0 60.4 <0.05
5/Treatment 8 SusNS OriginalsubstanceNS10.0 6.75±3.2
1.04±0.17
0.0 0.0 NA
a-fFortheabbreviaonsseefootnotesofTable2.
hp://bdvets.org/javar/ 1127
Marchenko et al. / J. Adv. Vet. Anim. Res., 11(4): 1122–1129, December 2024
Discussion
The diverse taxonomic composition of the internal parasite
complex in sheep, comprising nematodes, cestodes, trem-
atodes, and nasopharyngeal myiasis, necessitates the use
of broad-spectrum antiparasitic compounds for effective
treatment. Therefore, in this study, we formulated mech-
joint grinding with LE and Na-DSS and showed that the
for the elimination of target parasites in comparison with
original unchanged drugs given at recommended doses.
This observation can be explained by increased water sol-
ubility of the suspension forms, i.e., by a factor of 13.1 for
IM:LE:Na-DSS and 6.3 for NS:LE:Na-DSS compared to the
initial substances, which leads to higher bioavailability and
consequently antiparasitic activity [22,23].
In this regard, LE might have played an important role
in increasing the solubility of the suspension forms, i.e., by
a factor of 5.5 for IM:LE and 1.5 for NS:LE compared to the
initial substances. Indeed, LE contains 25% of a naturally
occurring metabolite, GA, which is a widely used medicinal
anti-allergy agent, and anti-psoriatic agent [24]. GA has the
ability to change the properties of cell membranes, even at
micromolar concentrations, and it can provide new insight
into the mechanism of enhancement of drug bioavailability
in the presence of GA. Researchers suggest this substance
as an effective drug carrier, which enhances the solubility
of low-soluble drugs, as well as enhances their penetration
through cell membranes [11]. Previous studies showed
that using GA and its derivatives for the mechanochemi-
-
tributes not only to increasing their solubility but also to
Table 4. Ecacyofsuspensionsamplesinsheepmonieziosis.
Experiment number/
group of animals # in group Test product Dose (mg of acve substance/
kg BW)
# remaining
parasitesaIEc % Efd % p-valuee
1/Control 10 Placebo 0 0.9±0.48
0.46±0.09 ---
1/Treatment 8 SusIN-3 ModiedIM0.2
ModiedNS3.0
1.0±0.5
0.42±0.06 0.0 0.0 NAi
2/Treatment 8 SusIN-5 ModiedIM0.2
ModiedNS5.0
0.62±0.32
0.2±0.1 31.2 56.5 >0.05
3/Treatment 8 SusIN-10 ModiedIM0.2
ModiedNS10.0 0.0 100 100 NA
4/Treatment 8 SusIM OriginalsubstanceIM0.2 0.87±0.4
0.3±0.12 3.4 34.8 >0.05
5/Treatment 8 SusNS OriginalsubstanceNS10.0 0.62±0.42
0.39±0.09 31.2 15.3 >0.05
a-fFortheabbreviaons,seethefootnotesofTable2.
Table 5. Ecacyofsuspensionsamplesinsheepestrosis.
Experiment number/
group of animals # in group Test product Dose (mg of acve substance/
kg BW)
# remaining
parasitesaIEc % Efd % p-valuee
1/Control 10 Placebo 0 11.2±2.8
1.18±0.06 ---
1/Treatment 8 SusIN-3 ModiedIM0.2
ModiedNS3.0
0.86±0.49
0.26±0.16 92.4 78.0 <0.05
2/Treatment 8 SusIN-5 ModiedIM0.2
ModiedNS5.0 0.0 100 100 NAi
3/Treatment 8 SusIN-10 ModiedIM0.2
ModiedNS10.0 0.0 100 100 NA
4/Treatment 8 SusIM OriginalsubstanceIM0.2 1.13±0.58
0.46±0.09 89.9 61.1 <0.01
5/Treatment 8 SusNS OriginalsubstanceNS10.0 10.6±3.6
1.05±0.14 5.4 11.1 >0.05
a-fFortheabbreviaons,seethefootnotesofTable2.
hp://bdvets.org/javar/ 1128
Marchenko et al. / J. Adv. Vet. Anim. Res., 11(4): 1122–1129, December 2024
been reported that complexing praziquantel (PZQ), the
most commonly used anthelmintic drug for treating trem-
atodoses, with disodium glycyrrhizinate in the 1:10, ratio
had higher bioavailability than PZQ substance and reduced
the number of Opisthorchis felineus helminths in the liver
by 87% [25,26]. In another study, joint mechanochemical
treatment of PZQ with disodium salt of GA (Na2GA) led to
particle sizes, amorphization of substance, incorporation
-
idant effects [12] was another substance we employed
to increase the water solubility of the formulations.
FBZ:LE:Na-DSS led to increased solubility of FBZ up to
27 times, which contributed to an increase in its perme-
ability through biological membranes and an increase in
the activity of the drug [10]. The reason behind the higher
anthelmintic action of FBZ:LE:Na-DSS was explained to be
the smaller size of FBZ, loss of crystallinity, amorphization,
and inclusion of its molecules on the surface and inside the
pores of polymers; the increase in solubility and permea-
bility through biological membranes [27].
As a limitation, in this study, we did not examine the
parasitocidal effectiveness of the formulations against
sheep ked Melophagus ovinus, which are common and
widespread. Future studies are needed to elucidate this
issue. Such results were achieved using data known in the
various methods.
Conclusion
This study demonstrated that the mechanochemical sol-
can lead to the development of new complex antiparasitic
frequency of treatment, thereby minimizing the negative
impact on the animals and promoting higher standards
of animal welfare. Furthermore, the preparation of drugs
using this technology is waste-free and safe both for pro-
duction and the environment [28].
List of abbreviaons
BW, body weight; DLS, dynamic light scattering; EE, exten-
of the number of helminth eggs of the experimental groups
in relation to the control; EPG, egg per gram of feces;
-
ogy; FBZ, fenbendazole; GA, Glycyrrhizic acid; IE, Intensity
Sodium dioctylsulfosuccinate; Na-CMC, Sodium salt of car-
boxymethyl cellulose; NS, niclosamide; PZQ, praziquantel;
SD, solid dispersion; SusIN; suspension of ivermectin and
niclosamide.
Acknowledgments
The research was carried out within the framework of
Agrobiotechnology (FASCA) No. 0790-2019-0037 with the
support of the Ministry of Science and Higher Education of
the Russian Federation (Contract No. 075-00277-24-00).
Conict of interests
had no role in the design of the study; in the collection,
analyses, or interpretation of data, in the writing of the
manuscript, or in the decision to publish the results.
Authors’ contribuon
Conceptualization, VAM and SSK; methodology, VAM, AS,
and SSK; validation, SSK and AS; formal analysis, VAM,
AS, and SSK; investigation, YAV, IVB, VAM, and MSK; writ-
ing-original draft preparation, VAM and SSK; writing-re-
view and editing, SSK and AS; visualization, VAM, AS,
and SSK; supervision, VAM and SSK; project administra-
tion, VAM and SSK; funding acquisition, VAM and SSK. All
authors have read and agreed to the published version of
manuscript.
References
[1] Marchenko VA, Khalikov SS. Supramolecular com-
plexes of drugs for parasitic sheep infestations. IOP Conf
Ser Earth Environ Sci 2020; 548:082006; https://doi.
org/10.1088/1755-1315/548/8/082006
[2] Charalabidis A, Sfouni M, Bergström C, Macheras P. The biophar-
-
lines. Int J Pharm 2019; 566:264–81; https://doi.org/10.1016/j.
ijpharm.2019.05.041
[3] Khalikov SS, Dushkin AV. Strategies for solubility enhancement
of anthelmintics. Pharm Chem J 2020; 54(5):504–8; https://doi.
org/10.1007/s11094-020-02229-4
[4] Da Silva FLO, De Freitas Marques MB, Kato KC, Carneiro G.
Nanonization techniques to overcome poor watersolubility with
drugs. Exp Opin Drug Discov 2020; 15(7):853–64; https://doi.
org/10.1080/17460441.2020.1750591
[5] Peter OI, Ifeoma UC. Development and evaluation of albenda-
zole microcapsule for colonic drug delivery system. UJPSR 2017;
2(2):26–9; https://doi.org/10.22270/ujpr.v2i2.R2
[6] Gamboa GVU, Pensel PE, Elissondo MC, Bruni SFS, Benoit JP,
Palma SD, et al. Albendazole-lipid nanocapsules: optimization,
with Echinococcus granulosus. Exp Parasitol 2019; 198:79–86;
https://doi.org/10.1016/j.exppara.2019.02.002
[7] Avgustinovich D, Lvova M, Vishnivetskaya G, Tsyganov
M, Orlovskaya I, Toporkova L, et al. Effects of three time
hp://bdvets.org/javar/ 1129
Marchenko et al. / J. Adv. Vet. Anim. Res., 11(4): 1122–1129, December 2024
administration of a supramolecular complex of praziquantel
with disodium glycyrrhizinate on trematode Opisthorchis felineus
in Hamsters. J Drug Deliv Sci Tech 2019; 50:66–77; https://doi.
org/10.1007/s11686-020-00329-5
[8] Tekade AR, Yadav JN. A review on solid dispersion and carriers
used therein for solubility enhancement of poorly water sol-
uble drugs. Adv Pharm Bull 2020; 10(3):359–69; https://doi.
org/10.34172/apb.2020.044
[9] Sun Y, Chen D, Pan Y, Qu W, Hao H, Wang X, et al. Nanoparticles
for antiparasitic drug delivery. Drug Deliv 2019; 26(1):1206–21;
https://doi.org/10.1080/10717544.2019.1692968
[10] Varlamova AI, Movsesyan SO, Arkhipov IA, Khalikov SS, Arisov
MV, Kochetkov PP, et al. Biological activity and pharmacokinetic
behavior of fenbendazole integrated into a supramolecular deliv-
ery system with licorice extract and sodium dioctyl sulfosucci-
nate. Biol Bull 2020; 47(6):565–74; https://doi.org/10.1134/
S1062359020060138
glycyrrhizin on permeability and elasticity of cell membrane:
perspectives for drugs delivery. Drug Deliv 2016; 23(3):858–65;
https://doi.org/10.3109/10717544.2014.919544
[12] Stolpovskaya NV, Zorina AV, Perelygina IE, Lyapun DV.
Physicochemical properties sulfosuccinates based on dietha-
nolamides of some fatty acids. Condens Matter Interphases [in
Russian Kondensirovannye Sredy i Mezhfaznye Granitsy] 2015;
17 (4):526–33.
Oestrus ovis L. (Diptera: Oestridae)
Siberia. Gorno-Altaisk State University, Gorno-Altaisk, Russia,
2021.
[14] Khalikov SS, Lokshin BV, Ilyin MM, Varlamova AI, Musaev MB,
Arhipov AI. Methods for obtaining solid dispersions of drugs and
their properties. Rus Chem Bull 2019; 68(10):1924–32; https://
doi.org/10.1007/s11172-019-2648-3
[15] Yang SC, Paik STR, Ryu J, Choi KO, Kang TS, Lee JK, et al. Dynamic
light scattering-based method to determine primary particle
size of iron oxide nanoparticles in simulated gastrointestinal
https://doi.org/10.1016/j.
foodchem.2014.04.022
[16] Khabriev RU. Guidelines for the experimental (preclinical) study
of new pharmacological substances. Medicine, Moscow, 2005.
[17] European convention for the protection of vertebrate animals
France, 1986.
[18] Kalashnikov AP, Fisinin VI, Shcheglov VV, Kleimenov NI. Norms
and diets for feeding livestock. Rosselkhozakademiya, Moscow,
Russia, 2003.
[19] Kondrakhin IP. Methods of veterinary clinical laboratory diagnos-
tics. Kolos, Moscow, Russia, 2004.
[20] Wood I, Amaral NK, Bairden K, Duncan JL, Kassai T, Malone JB,
et al. World ssociation for the advancement of veterinary para-
sitology (WAAVP) second edition of guidelines for evaluating
the effectiveness of anthelmintics in ruminants (bovine, ovine,
caprine). Vet Parasitol 1995; 58(3):181–213; https://doi.
org/10.1016/0304-4017(95)00806-2
[21] Selyutina OY, Polyakov NE. Glycyrrhizic acid as a multifunc-
tional drug carrier—from physicochemical properties to bio-
medical applications: a modern insight on the ancient drug.
Int J Pharm 2019; 559:271–9; https://doi.org/10.1016/j.
ijpharm.2019.01.047
[22] Arkhipov IA, Sadov KM, Limova YV, Sadova AK, Varlamova AI,
of niclosamide obtained by mechanochemical technology and tar-
geted delivery against cestode infection of animals. Vet Parasitol
2017; 246:25–9; https://doi.org/10.1016/j.vetpar.2017.08.019
[23] Marchenko VA, Khalikov SS, Vasilenko YA, Ilyin MM, Kravchenko
IA. Innovative anthelmintic based on mechanochemical tech-
Adv Vet Anim Res 2020; 7(4):718–25; http://doi.org/10.5455/
javar.2020.g473
[24] Chauhan S, Gulati N, Nagaich U. Glycyrrhizic acid: extraction,
Pharmaceutica 2018; 59(2):61–7; https://doi.org/10.30827/ars.
v59i2.7513
[25] Arkhipov I, Khalikov S, Dushkin A, Sadov K, Meteleva E, Arisov
praziquantel obtained by mechanochemical technology. Iran J
Parasitol 2020; 15(3):364–73; https://doi.org/10.18502/ijpa.
v15i3.4201
fenbendazole on the basis of nanosized supramolecular delivery
systems with polyvinyl pyrrolidone and dioctylsulphosuccinate
sodium in the cases of helminthosis. Rus J Parasitol 2019; 13(1):56–
63; https://doi.org/10.31016/1998-8435-2019-13-1-56-63
[27] Khalikov SS. Solid dispersions of anthelmintics and plant
protection preparations. Solids 2021; 2:60–75; https://doi.
org/10.3390/solids2010003
[28] Khalikov SS. Mechanochemical technology for regulation of the
solubility of anthelmintic drugs by using polymers. Ineos Open
2021; 4(2):53–60; https://doi.org/10.32931/io2108r
