Tipo di tesi
Tesi di laurea specialistica
Studi in vivo di nuove formulazioni di Acyclovir per il trattamento di herpes genitalis.
SCIENZE MATEMATICHE, FISICHE E NATURALI
Corso di studi
SCIENZE E TECNOLOGIE BIOMOLECOLARI
relatore Prof. Mauro Pistello
Data inizio appello
Data di rilascio
Herpes genitalis is one of the most common sexual transmitted diseases (STD).
Recent studies demonstrate that herpes genitalis ranks 5th among top ten STD in the world and increases constantly. The infection is caused by Herpes Simplex Virus type-1 and -2 (HSV-1, HSV-2) easly transmitted to sexual partners and progeny. Herpes genitalis can develop subclinically or characterized by recurrent pain, ulceration, and an increased risk of contracting other STD, such as human immunodeficiency virus.
Due to the high impact on public health, it is crucial to prevent the spread of the disease through both effective preventative vaccines and\or suitable pharmacological therapies. Unfortunately, no effective vaccines anti-HSV are available and Acyclovir (ACV) and it’s derivates, although effective and well-tolerated, are rapidly eliminated by clearance. Then, to avoid selction of ACV-resistant strains, effective therapy requires daily high dosage.
ACV is a nucleoside analogue, in which the sugar ring is replaced by an open chain structure. ACV is selectively converted into acyclo-guanosine monophosphate (acyclo-GMP) by HSV enzime thymidine kinase. The activated form is then incorporated by DNA polymerase into nascent DNA chain, thus blocking it’s elongation. ACV has low cytotoxicity. But although many studies have tried to improve the bioavailability, the biological half-life of ACV is only 3 hours.
Aim of the study is to test a new delivery system to increase ACV biological half-life, reduce dosage and frequency of administrations as well as to test the efficiency of an anti HSV-2 microbicide.
The experiments have been were carried out on C57Bl/6 mice, that have been infected via vagina with virulent HSV-2 isolate and treated with ACV commercially available or formulated with nanoparticles. We found no difference between the delivery systems, if administrated daily. Similar results were obtained by administrating the ACVs Every other day. Other tests have been performed to compared the efficiency of both drugs, when administrated every other day. These tests demonstrated that vehiculation with nanoparticles does not confer higher efficiency than marketed. New studies are necessary to improve the bioavailability.
In contest, the microbicide applied fifteen minutes before challenge, have proved effective in preventing the infection, Efficiency however depends on viscosity of the preparation.
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