INTRODUCTION:

Helminths are a group of parasites that cause serious health problems in animals worldwide. Although management of livestock pastures can reduce the effect of parasites, these methods are not sufficient to eliminate these parasites. In many countries, the use of anthelmintics, which covers the majority of healthy animals, is widely used to control helminthiasis. source of infection. Anthelmintic control has been successful in the last 50 years due to the high efficacy of anthelmintic drugs (more than 95% reduction in bacteria), all data have good safety, are general and affordable.

Unfortunately, the intensive use of antibiotics has led to serious and severe anthelmintic resistance (AR), especially in intestinal nematodes of cattle, sheep, goats and horses. With humans. AR has been reported in all classes of anthelmintics. The time between the introduction of antibiotics and the development of resistance appears to be less than 10 years. The process is influenced by the following factors: host, parasite, type of anthelmintics and their use, animal management and weather conditions.¹ Therefore, there is more competition in the development of control and prevention methods that will differ among production lines. The cooperation of many factors, the difficulty of developing new antibiotics and the difficulty of converting resistant bacteria into susceptible bacteria are very important in the development of AR. To date, anthelmintics have not been developed and effective strategies have not been developed to control helminth infections. Therefore, regular AR research and understanding of the consequences and mechanisms of anthelmintic resistance are important to reduce the spread of anthelmintic resistance. Therefore, the main purpose of this review is to introduce AR, its emergence, development process, findings and strategies to delay the development of AR. Causes of (AR) “parasite survival to treatment and pass on resistance-associated genes to their offspring”. Resistant species are, a priori, morphologically non-differentiable from non-resistant species and AR must be distinguished from therapeutic failures in which the persistence of parasite is due to inappropriate administration of treatment. In the initial phase of AR, the number of resistant parasites within a population is low. AR is a serious problem affecting small ruminants, cattle and horses. Many years of use of anthelmintic drugs have generated great resistance to them in GIN. Although sound herd management is essential, this is not enough to combat GIN, making it necessary to carry out studies on alternatives to traditional drugs. New synthesized molecules do not eliminate the problem of AR, as these new AH also produce resistances. An approach to the problem must take in other perspectives, such as genetic.²

Anthelmintic Resistance and Its Mechanism Again the Parasite:

Definition of Anthelmintic Resistance:

AR is the genetic loss of sensitivity to a particular anthelmintic drug in a bacterial population that was previously sensitive to that drug. It is thought that AR occurs when a population loses sensitivity to anthelmintic drugs when there is a higher proportion of parasites in the same species than in the population, and is passed on from generation to generation. there are three types of AR: cross-resistance, side-resistance, and multiple resistance. Cross-resistance is also the first type of protection that parasites can use to avoid treatment with anthelmintics or anthelmintics that have different functions. The second type of resistance is side-resistance, which is resistance produced against an anthelmintic by selection of another anthelmintic with a similar mechanism of action. Resistance to benzimidazole anthelmintics is considered an example of secondary resistance. Secondary resistance to morantel has also been reported in strains resistant to levamisole. The development of resistance to two or more anthelmintics with similar or different mechanisms of action, due to independent selection or protection by each human group, is a third type of anthelmintic resistance and is called multidrug resistance.³

Current Situations of Anthelmintic Resistance Again Parasite:

The development of AR is common in different helminths in almost all animal species and in many countries to different anthelmintic groups. The results of several scientific studies in Europe have shown that the resistance of bacteria to well-known anthelmintic drugs such as benzimidazole, ectoine, imidazothiazole and macrolides is increasing to different extents. A cross-sectional study by Mickiewicz et al. showed the presence of AR to BZ, ML and LEV in Polish goat farms, with high resistance to BZ and ML and low resistance to LEV. Potàrniche et al. also reported the resistance of Romanian goat intestinal nematodes to MLs and BZs, which is the first report in this country.⁴ Furthermore, individual data show that bacteria have developed resistance to new classes of anthelmintics (e.g. Haemanthus contorts has developed resistance to monepantel, C and aminoacetonitrile derivatives). Studies have shown that resistance to anthelmintic drugs is developing, and in some countries, it has been banned because sheep and goats are resistant to antibiotics. The time from the introduction of anthelmintic drugs to the development of resistance appears to be less than 10 years. In sheep, resistance to imidazothiazole, ectoine and avermectin-milbemycin occurs within three to nine years.⁵ The seriousness and extent of the problem, especially multidrug resistance in nematode populations, needs to be increased. Several authors have reported multiple reactions to benzimidazole, imidazothiazole and macrolides in sheep Haemonchus contortus, Trichostrongylus contortus and Trichostrongylus trichostrongylus throughout Europe. The severity of the parasite has been exaggerated by the widespread use of antibiotics in many tropical countries and the increase in parasite-specific diseases. The trend towards overuse of drugs in animals also poses a threat to public health. Government agencies do not understand or ignore the mechanism of this emerging problem.⁶ In Ethiopia, there are three anthelmintic families of antibiotics commonly used to treat intestinal helminth infections in livestock: benzimidazole (such as albendazole and triclabendazole), imidazole thiazoles (such as tetraimidazole and levamisole), and macrolides chin. Illegal and inappropriate use of antibiotics has led to failure to eradicate intestinal parasites in livestock and has led to the emergence of AR of many nematode diseases in different regions of Ethiopia. Wondimu and Bayu15 from Haramaya, Ethiopia reported the presence of intestinal parasites multi-resistant to albendazole, tetraclosan, ivermectin, and tetramidazole in goats among Trichostrongylus spp., Tradossagi subgenus. and Haemonchus spp. is a type species in post-modern culture. Mphahlele et al reported the prevalence of AR against intestinal nematodes infecting sheep in the Limpopo Province of South Africa.⁷

Frequency of Treatment:

This is an important factor that determines the speed of AR development. Resistance to anthelmintics will develop more rapidly when anthelmintic treatment is repeated. The basic principle in choosing AR is that the treatment allows the surviving organism to recover and recover from the susceptible organism for approximately two to three weeks after antibiotics.⁸

Administration of anthelmintics:

Overdose is generally considered a factor in the development of AR, as subtherapeutic doses can increase survival of heterozygous anti-anthelminthics. Some laboratory experiments have shown that poor performance results in the selection of resistant or tolerant bacteria. In addition, differences in bioavailability between species are important in determining the correct dosage. Some regional evidence also supports this conclusion. For example, benzimidazole and levamisole are less bioavailable in goats than in sheep, so the dose for goats should be 1.5 to 2 times higher (one dose is better than the “suboptimal dose”) than for sheep, which is close to half the dose for goats. However, sheep and goats have been given the same wormicidal dose for many years. The fact that AR is so active and widespread in goats may be a direct result of differences in drug metabolism. In developing countries, it has been suggested that lower doses be used to reduce the cost of anthelmintic therapy. This should obviously be avoided. In fact, most anthelmintics are now effective for at least some humans. In addition, there are numerous nematode species in mixed livestock worldwide, and these nematodes respond differently to different groups of anthelmintics, as they are insensitive to specific antibiotics. This is necessary for disease control, but such strategies may also lead to the development of AR in the long term.⁹

Anthelmintics Drug and Resistance Treatment:

Anthelmintics are used to prevent rather than cure disease. EG95 is a vaccine against zoonotic echinococcosis or hydatid disease. Many vaccines are under development, such as TSOL-18 against neurocysticercosis caused by Taenia solium and Hc-23 against Haemonchus contortus, but there are many other diseases that are parasitic diseases for which antibodies have not yet been developed. antibodies have not yet been developed or the development of antibodies is still in their infancy. Treatment is usually dependent on chemotherapy. However, these chemotherapy drugs are associated with drug reactions. Anthelminthic drugs are less sensitive to parasites that were previously sensitive to the drugs. This is a hereditary mutation because it is transmitted through genes, which makes the situation worse. Anthelmintics have also become a problem.¹⁰

Violation of pest control laws is frequently seen in the field. Anthelmintic resistance (AR) is thought to arise due to parasitic or control factors. Genetic variation is also thought to be important in the development of immunity. The first cases of anthelmintics occurred in sheep reared at a research centre in Kentucky, USA, in the mid-1950s, where phenothiazines failed to treat schistosomiasis. Resistance to many of the best commercial anthelmintics has become a serious problem worldwide. Resistance to all three broad families (benzimidazole, ivermectin and imidazole) has been documented worldwide. Resistance to narrow-spectrum drugs such as salicylanilide has also been observed. The prevalence of AR has been confirmed by recent studies, particularly in C. elegans. AR has gained commercial and clinical importance in some parts of the world, particularly in Trichostrongylus species that infect sheep and goats. The problem seems to have become more serious with the emergence and spread of multidrug resistance in small ruminants. The gap between the increasing evidence of AR on the one hand and the uncertainty of the true helminth population in a group of animals is a problem that needs to be resolved.¹¹

Targeting and Timing of Mass Treatment:

Research shows that aggressive treatment can help AR, but the development of resistance can be delayed by treating about 80% of the herd.

Anthelmintic Dose Rates:

The incorrect and inappropriate use of anthelmintics is one of the main factors contributing to the development of AR. Estimated weight is the most used method in veterinary medicine to determine the dosage of anthelmintics and general drugs, and is often unnecessary and can lead to relapse. This low dose allows the survival of heterozygous resistant worms and therefore contributes to the selection of resistant strains.¹²

Genetics:

Resistant parasites pre-existing in the parasite. AR is now considered to have pre-emerged, with resistant alleles present in the parasite before the anthelmintic agent in question is discovered to be present in the infected parasite. In the absence of anthelmintics, natural selection maintains resistant alleles at a low frequency because resistant alleles make the worms carrying them less fit to survive than susceptible organisms. However, the introduction and continued use of anthelmintics has given antibiotics a chance to survive. This allows them to multiply more rapidly than severe disease, increasing the frequency of resistant phenotyped diseases in the population. Finally, the frequency of worms with a resistant phenotype increases to the point at which resistance to anthelmintics is said to have occurred or developed. Although anthelmintic resistance is a latent trait of the worms, only homozygous worms can tolerate the appropriate anthelmintics. Anthelmintics can kill heterozygous bacteria.¹³

Mechanism of Anthelmintic Resistance:

Understanding the mechanisms of resistance can help researchers better predict how rapidly resistance will occur and can provide tools for studying parasite biology and treatment targets. The mechanisms of anthelmintic resistance generally involve (1) regulation of cellular efflux mechanisms, (2) increased drug metabolism, (3) alterations in the drug receptor site, reduction of the chemical or functional effect of drug binding, or (4) reduction of drug receptor abundance through reduction or other reduction methods. The relationship between the above alterations and resistance of different helminth species.¹⁴

Macrocyclic Lactone Resistance:

Resistance to similar drugs such as ivermectin is also found in macrolides. Due to their long history of use, the terms avermectin and milbemycin resistance are often used to refer to helminth populations resistant to macrolides. Ligand-gated chloride channels are the most common target of ML therapy, and mutations in genes encoding these proteins have been shown to cause AR. The occurrence of GluClR mutations was first described in a paper on the mechanism of ivermectin resistance in parasites. Alleles of the GluCla subunit gene were frequently found in Haemonchus contortus isolates resistant to ivermectin and moxidectin, suggesting that mutations in this gene are associated with ML resistance.¹⁵

Protein transporters, particularly P-glycoproteins (Pgps), serve as an efflux mechanism to transport molecules across cell membranes, thereby reducing their intracellular concentration. This prevents the drug from reaching its target. Ivermectin has also been reported in H. contortus associated with Pgps. PGP-2 is the Pgp most commonly identified as associated with ML resistance. Enzymes involved in drug metabolism are the other nonspecific processes most likely to cause macrolide resistance. Recently, Yilmaz et al reported that CYP34/35 expression is increased in many immune and infectious diseases compared to diseased subjects.¹⁶

Resistance to Benzimidazoles:

The mechanism of resistance to benzimidazole anthelmintics is clearly linked to mutations in β-tubulin. Resistance to BZ can result from mutations at tyrosine 200 phenylalanine in isotype I α-tubulin.

Even a single amino acid change in tubulin results in blockade of benzimidazole binding in resistant nematodes. BZ-resistant gastrointestinal nematode (GIN) strains are associated with three nonsynonymous single nucleotide polymorphisms (SNPs) in the isoform 1-tubulin gene. The most common SNP results in a change from phenylalanine to tyrosine at position 200 (F200Y), while other SNPs result in a change from phenylalanine to tyrosine at position 167 (F167Y) or from glutamic acid to alanine at position 198 (G198Y).¹⁷

Imidothiazoles and Tetrahydro pyrimidines Resistance:

The activity of nicotinic acetylcholine receptors (nAChRs), particularly the L-type receptor subset favored by levamisole and pyrantel, has been the focus of research into the cause of resistance to these nicotinic agonists. When L-nAChRs are activated, they cause neuromuscular depolarization and spastic paralysis. There is some evidence that target mutations in the nematode environment may be mechanisms of resistance to levamisole and pyrantel among several species of Trichostrongylus nematodes. Downregulation of genes encoding the nACh subunits that produce the receptor has been shown to increase the resistance of H. contortus and A. They are canines. H. contortus, T. colubriformis and T. circuccincta isolates have short forms of two receptor subunits (acr-8b as a truncated form of acr-8a and unc-63b as a truncated form of unc-63a). are also involved in protection.¹⁸

Methods for Detection of Anthelmintic Resistance:

There are a few things to consider before testing AR. First, remember that many diseases can cause symptoms similar to common diseases. Second, anthelmintic treatments may fail to control nematodes because other treatments have failed. Failures in these cases are often due to issues such as water supply failure or improper weight measurement. With the rise of AR, the need for reliable and accurate detection methods is also increasing. In vivo and in vitro methods are used in the diagnosis and follow-up of AR.¹⁹

In vivo Methods:

Fecal Egg Count Reduction Test (FECRT):

The efficacy of the drug is determined by comparing the eggs of animals before and after treatment. The test has been rigorously evaluated to allow its widespread use. According to FECRT, protection is evident when two requirements are met: when the egg percentage is less than 95 percent and when the lowest of the 95 percent confidence levels is equal to or less than 90 percent. After benzimidazole treatment, egg counts should be performed 10–14 days after antibiotic use. Anthelmintic treatment is best used because it temporarily stops egg laying but does not kill adult nematodes. If the average duration of treatment is less than 10 days, the number of eggs will decrease, which will lead to an overestimation of the antibiotic use of benzimidazole anthelmintics. Therefore, it is recommended to collect stool within 10-14 days after treatment. If resistance to levamisole is suspected, stool should be collected within 7 days after treatment. Therefore, the duration of treatment and the second egg vary according to the group of anthelmintics: 7-10 days for benzimidazole, 3-7 days for ectoine, 14-17 days for imidazothiazole, macrolides.²⁰

In vitro Methods:

Egg Hatch Assays (EHAs):

Benzimidazole anthelmintics inhibit embryonic development and hatching of nematode parasite eggs. This device was developed to detect anthelmintic drugs. This test is not suitable for use with ectoine, imidazothiazoles and macrolides because they have no ovicidal effect. In the experiment, fresh eggs were placed in each well of a 24-well plate and incubated at 27°C for 48 hours, then various concentrations of benzimidazole (0.5, 1, 2, 3, 5 ppm) were added and the remaining eggs were counted for larvae to hatch and the LD50 value was calculated. This is a more effective way to diagnose benzimidazole resistance.²¹

Larval Development Test (LDT):

This test is based on the capacity of larvae to survive and develop in varied anthelmintic medication concentrations. The development of larvae (from eggs of a pooled fresh feces sample in a sub-group of the flock) under various doses of the anthelmintic is examined in larval development tests. Incubation can be done either on a liquid or a solid nutritional medium (agar). AR against the major anthelmintic families is detected using this approach. Variations in LD50 (larval 50% death) have been reported in this test depending on the timing of infection, especially when macrocyclic lactones (ML) are utilized. Some veterinary offices and regional veterinary laboratories offer this test.²²

Larval Motility Test (LMT):

Larvae three are incubated at 25°C for 24 h in various concentrations of drug while in the dark. Then they are exposed to light for 20 min to stimulate those not paralyzed. After that the number of nonmotile larvae as proportion of the total larvae present at each drug concentration are calculated.²²

Polymerase Chain Reaction (PCR):

This PCR-based technology allows genotyping of resistant (rr) or susceptible (rS and SS) adults or larvae. Using four primers in the same reaction mixture, worms can be genotyped for the change in β-tubulin residue 200 (phenylalanine to tyrosine) associated with BZ resistance.²³

Anthelmintic Management methods to delay the development of resistance:

The use of antibiotics to control livestock helminths over the past five years has led to the development of resistance blocks for all major anthelmintic classes. The development of new anthelmintics to control resistance is a slow and expensive process. It is therefore important that existing antibiotics are used in a way that reduces the effect of AR.²³

Various management methods, such as orchard management and housing, have been suggested to prevent parasitic diseases and/or keep disease levels low. These will reduce the need for anthelmintics, which will delay the development of AR. The main actions to be taken to slow down the development of AR are the correct use of antibiotics, the reduction of antibiotic dependency, the implementation of preventive measures on the farm from the moment the animals arrive, the isolation is started, and control is ensured. The population is combated with anthelmintic diseases and regularly controlled anthelmintic resistance.²⁴

Correct Use of Anthelmintics:

It is thought that the persistence of AR occurs when the helminth population is exposed to anthelmintics. Surprisingly, the risk of developing resistance increases when the dose is inadequate and the same class of anthelmintics is used repeatedly. It has been suggested that anthelmintic classes be rotated to slow the development of resistance. Using reliable diagnostic tests to identify the type of parasite, using the correct anthelmintic based on the diagnosis, and following instructions for appropriate dosing and administration are important strategies for delaying anthelmintic resistance.²⁵

Refugia:

Preventive measures should focus on slowing antibody accumulation, and strategies to slow the development of resistance should be implemented early in the prevention transition, before evidence of diminishing drug resistance emerges. The best way is to follow rules that satisfy the refuge; anthelmintic resistance is present in the parasite and cannot be reversed or lost once resistance is established. Refuges limit the development of resistance by allowing the protection of victims and the dilution of offspring of resistant organisms that survive treatment. The rate of evolution slows as the refuge grows.²⁶

Use of Combined Anthelmintics:

The use of antibiotics with related activities as a way to reduce AR development has been suggested, but different models are being proposed. Due to the development of resistance to imidazothiazole and ectoine, there has recently been increased interest in the use of different classes of antibiotics to control the presence of resistant nematodes and slow down the growth of resistant individuals.²⁷

Other Options:

Reducing the frequency of anthelmintic usage is very useful to decrease the rate of AR development. Applying a better grazing management is a possible and helpful method to reduce the frequency anthelmintic use. Lowering of the stocking rate and the grazing period on the pastures, and applying mixed grazing among different animal species are key factors for a better grazing practice. Applying biological control is also a remarkable technique to reduce the use of anthelmintics. The main principle in biological control is using natural enemies that can eat/kill the parasites to decrease the infection level on pastures. These treatments do not attempt to eliminate free-living larval stages, but rather to lower them to a point where they have minimal clinical or subclinical impact while promoting an acquired immune response. Selecting genetically less vulnerable animals is one method that has been tried to lessen the helminth burden in animals.²⁸

The development of efficient vaccines against intestinal parasites will allow antiparasitic medications to be used less frequently. Despite significant attempts to develop vaccinations to protect grazing animals from helminth infections, only a vaccine for the Dictyocaulus viviparus is currently commercially available.²⁹

Factors contributing to AR:

1. Frequent use of anthelmintics This factor holds significant influence over the pace at which AR advances. The acceleration of resistance to anthelmintic treatment occurs more rapidly when the administration of anthelmintic takes place at higher frequencies. The guiding principle in the selection process for AR is that treatment confers a reproductive and replication advantage upon the surviving parasites in comparison to the susceptible parasites, during a period of approximately 20-22 days following the administration of anthelmintic.³⁰

2. Anthelmintic dose rate : One of the main causes that may lead to the development of AR is the administration of an inaccurate or unsuitable dose of anthelmintics. In veterinary medicine, visual weight estimation is the most widely used technique to calculate the dosage rate of a drug, namely an anthelmintic, however it is frequently erroneous and can result in underdosing. Consequently, this underdosing aids in the selection of resistance strains by enabling the survival of heterozygous resistant worms.³¹

3. Underdosing: Administering anthelmintics at suboptimal doses allows resistant parasites to survive and reproduce, leading to an increase in the frequency of resistance alleles in the parasite population.

4. Misuse of anthelmintics: Misuse of anthelmintics, such as treating animals when they are not infected or using the wrong type of anthelmintic, can also contribute to AR.³²

5. Genetics of the parasite: The genetic makeup of the parasite population can influence the rate at which AR develops. Some parasite species are more prone to developing resistance than others.

6. Refugia: Refugia are areas where parasites are not exposed to anthelmintics, such as wildlife reservoirs. These refugia can provide a source of resistant parasites that can reinfect treated animals.

7. Targeting and timing of mass treatment: Mass treatment programs can contribute to AR if they are not carefully planned and implemented. For example, treating all animals in a herd at the same time can lead to the rapid selection of resistant parasites.³³

8. Overgrazing and poor pasture management: Overgrazing and poor pasture management can lead to increased parasite infection rates, which can put additional pressure on anthelmintic use and contribute to the development of AR.

9. Lack of effective monitoring and surveillance: Without effective monitoring and surveillance, it is difficult to track the spread of AR and develop effective control strategies^.34^,³⁵^,³⁶

Applications of Nanobiotechnology in Parasitology:

Parasitic infections are associated with significant morbidity and mortality worldwide (1). Therefore, the best strategy to solve the above problems related to parasitic diseases is to develop new biotechnologies that increase the efficiency and specificity of diagnosis and avoid drugs that prevent existing diseases. In this review, we will discuss some applications of nanobiotechnology in the diagnosis and treatment of parasitic diseases. Observe the patient's symptoms. However, treatment may not be effective once symptoms appear, so the earlier it is caught, the better the treatment. The best scenario is to diagnose and treat the parasite before symptoms appear. Nucleic acid diagnostics play an important role because parasites can be detected asymptomatically early, which has a good understanding for effective treatment. Biotechnology offers a solution. Small particles in nanobiotechnology can withstand more excitation cycles and light emission compared to more easily degraded organic molecules (2).³⁷ Quantum dots have found new applications in different bioimaging applications and in vitro diagnostics due to their broad distribution, high photostability, and tunable narrow emission spectral properties. These fluorescent properties of quantum dots make them powerful fluorophores for labeling organisms including organs, red blood cells (RBCs), genes, and proteins. QDs can also be used as probes for drug screening (2). bacteria and Giardia duodenalis. The different colors of the quantum dots for these antibodies work as immunoassay labels and are then linked to the specific antibodies detected. Quantum dots in immunofluorescent labeling of Cryptosporidium parvum oocysts demonstrate high consistency and significance in water samples (2). Magnetic Imaging Results. Nanosphere (Northbrook, IL) is a company developing technology for optical manipulation of the genetic structure of biological samples.³⁸ As with all genetic diseases, gold nanoparticles (NPs) with short DNA segments facilitate the readout of assays. If the target sequence is present in the sample, it can bind to complementary DNA tentacles of many nanospheres and form a dense network of visible gold spheres. Enteric Infection Assay (Enteric Infection Assay), Cary-Blair, and nonformalin fixatives (e.g., Total-Fix, EcoFix) are the first sample-to-result assays that will directly detect eight enteric pathogens from feces in Tao parasites. In addition to diagnosing intestinal diseases, EP Flex will simultaneously detect 8 enteric pathogens, 5 enteric pathogens, and 4 toxin-mediated enteric pathogens. The assay was performed on Nanosphere’s Verigene Flex system, a new model-profit, high-throughput platform that utilizes Nanosphere’s gold nanoparticle chemistry in a user-friendly format (3). Biological phenotypes, proteins play important roles and represent functions in healthy and unhealthy states. Therefore, proteomics is important in diagnostics and medicine, which can be manipulated by medicine. Small or chemical substrates can also be used to make protein wafers; In recent years, drug proteomics has been developed as a more powerful strategy for drug target discovery. This approach uses small drug-like molecules that can bind to ligands immobilized on a support or exposed to a protein layer. Proteins that bind to the ligand are then identified as drug targets.³⁹

Nanocapsule:

A nanocapsule is a nanoscale shell made from a nontoxic polymer. They are vesicular systems made of a polymeric membrane which encapsulates an inner liquid core at the nanoscale. Nanocapsules have many uses, including promising medical applications for drug delivery, food enhancement, nutraceuticals, and for self-healing materials. benefits of encapsulation methods are for protection of these substances to protect in the adverse environment, for controlled release, and for precision targeting. Nanocapsules can potentially be used as MRI-guided nanorobots or nanobots, although the challenges remain.⁴⁰ Dispersed polymer nanocapsules can serve as nano-sized drug carriers to achieve controlled release as well as efficient drug targeting. The dispersion stability and the primary physiological response are mainly determined by the type of the surfactant and the nature of the outer coating. Their release and degradation properties largely depend on the composition and the structure of the capsule walls. Another important criterion is the capsule size, where an optimum is generally seen for radii ranging between 100 and 500nm. Nanocapsules can be prepared by four principally different approaches: interfacial polymerization, interfacial precipitation, interfacial deposition, and self-assembly procedures. All these procedures offer their individual advantages and disadvantages when it comes to the design of optimized drug carrier systems.⁴¹

Nanovaccines:

In recent years, there are many ways to treat aquatic diseases. Further advances in nanotechnology have opened up new ways to create better vaccines. Nanovaccines are new generation vaccines that use nanoparticles as carriers or adjuvants. Various antigens can be encapsulated or adsorbed onto the surface of nanoparticles for application. Nanopreparations can be prepared from various materials such as polylactic-co-glycolic acid (PLGA), chitosan, gold nanoparticles, liposomes, etc. Each product has its advantages and disadvantages. Nanovaccines have many advantages over traditional vaccines. Nanoparticles can be a potential material for vaccine delivery.⁴² Oral administration in aquaculture is a simpler and more economical way to ensure delivery as it eliminates laborious and complicated procedures. For this purpose, nanoparticles protect the antigen from degradative enzymes and provide sustained release. Due to its small size, it is effective in enhancing the immune system and humoral strength. This section is designed to provide insight into the prospects for using nanotechnology to improve aquaculture health. The introduction of new technologies should accelerate the production of medically suitable nanoparticles. Despite their widespread use, there are questions about the different biological effects exhibited by some nanoparticles.

Nanovaccines consist of nanoscale materials attached or specially prepared with immune-supporting components. Nanovaccines have been shown to enhance the immune system’s ability to fight and prevent the spread of diseases.⁴³

CONCLUSIONS:

The intensive anthelmintic use for the management of helminths in livestock has led to the development of AR, which is a highly multifaceted process and affected by the treated animal, the parasite, type of anthelmintic and its utilization. Misuses of anthelmintic such as underdosing, treatment of all animals at the same time on the same farm, continued administration of the same anthelmintic, substandard quality, and frequent use of anthelmintic are very important contributors to AR development. Upregulation of cellular efflux mechanisms, an increase in drug metabolism, a change in drug receptor sites that reduces drug binding or the functional consequences of drug binding, and a decrease in drug receptor abundance through reduced expression within the parasite are the main mechanisms of anthelmintic resistance. Nowadays, apart from application of anthelmintics there are no other effective options to control parasitic helminths. In addition, the development of new anthelmintics to manage AR is a slow, as well as expensive, process. Hence, it is crucial to use the existing anthelmintics in a way that minimizes the impact of AR such as proper and combined utilization of anthelmintics and reducing dependence on anthelmintics. Regular detection and monitoring of AR development is also crucial.

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Received on 07.10.2024 Revised on 28.10.2024

Accepted on 11.11.2024 Published on 08.03.2025

Available online from March 12, 2025

Res.J. Pharmacology and Pharmacodynamics.2025;17(1):25-33.

DOI: 10.52711/2321-5836.2025.00005

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