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العنوان
Effect of triclosan and triclosan loaded lipid based nanoparticles (liposomes) in treatment of experimental toxoplasmosis/
المؤلف
Younis, Salwa Sami Abd El-Megid.
هيئة الاعداد
باحث / سلوى سامى عبد المجيد يونس
مشرف / هبه سعيد رمضان
مشرف / شيرين فاروق مسلم
مناقش / هويدا اسماعيل حسين
مناقش / إيمان رأفت إبراهيم
الموضوع
Medical Parasitology.
تاريخ النشر
2013.
عدد الصفحات
95 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الطب
تاريخ الإجازة
9/10/2013
مكان الإجازة
جامعة الاسكندريه - كلية الطب - Medical Parasitology
الفهرس
Only 14 pages are availabe for public view

from 167

from 167

Abstract

T.gondii is an obligate apicomplexan intracellular parasite, with an enteroepithelial cycle in the definitive host (domestic cats and other members of the family Felidae), and an extraintestinal cycle in intermediate hosts (many mammals including man and birds). It gets transmited by consumption of infected meat, by faeco-oral route, accidentlly in the laboratory or congenitally.
T. gondii infection in an immunocompetent host is not a major problem, while in immunocompromised people, it can develop severe systemic, ocular or most commonly neurological disease. In congenital infection, the severity varies according to the time of gestation at which infection occurs. Early infection in gestation tends to be severe with overt neurological and ocular involvement at birth, whereas those infected late in gestation may not exhibit disease at birth. Nevertheless, they develop ocular lesions at some point in their lives, usually during puberty. Those people need long-term management.
Currently, there is no vaccine available to prevent human infection with this pathogen. Antifolate agents, sulfadiazine and pyrimethamine, are two primary drugs for the treatment of T. gondii infection in humans. Alternative treatment options; azithromycine, clarithromycin, trimethoprim/sulfamethoxazole, artemisinin and atovaquone, are of variable efficacy. Although these medicines are effective against tachyzoites in the acute stage of the disease, they do not eradicate encysted latent bradyzoites. Furthermore, these therapies can be associated with side effects such as bone marrow depression, hypersensitivity and skin rashes. There is an urgent need to develop new anti-T. gondii medicines that are both efficacious and nontoxic to humans.
In apicomplexans, type II fatty acid synthesis (FAS-II) enzymes are present in a plastid organelle (apicoplast). Fatty acids play a critical role in cells; they act as metabolic precursors for biological membranes and energy stores. Triclosan (TS) is the antimicrobial agent, 5-chloro-2-[2, 4-dichlorophenoxy] phenol, that is known to impair FAS activity in bacteria and plants by inhibiting the enoyl acyl carrier reductase (ENR) enzyme. It was tested on malaria parasites as a potential novel drug.
It was found that micromolar concentrations of TS dissolved in DMSO inhibit replication of apicomplexan parasites, presumably by binding to, and inhibiting, apicomplexan ENR. To eliminate apicomplexan parasites, inhibitory compounds must cross host cell, parasitophorous vacuole and parasite membranes, besides the body barriers as the gastrointestinal barrier when using the oral route. In addition to, the cyst wall of the brain cyst of T. gondii and the blood brain barrier to reach the brain cysts which make delivery challenging.
Poor solubility of TS is one of its physico-chemical properties which limits its therapeutic use. Nanoparticulate systems have great potentials, being able to convert poorly soluble, poorly absorbable and labile biologically active substance into promising deliverable drugs. Liposomes are classical examples of lipid-based nano-based systems that can be used to entrap and release drug without side effects.
Accordingly, this work was designed to evaluate the efficacy of TS and TS liposomes against avirulent and virulent strains of T. gondii in the mouse model.
In fulfillment of this aim, the study was conducted on two hundred and ten laboratory bred Swiss strain Albino mice. Seventy mice served as control group