الفهرس 
SchistosomiasisOnly 14 pages are availabe for public view
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Abstract
Praziquantel (PZQ) is a pyrazinoisoquinoline derivative with anthelmintic
activity which was discovered in 1972 by E. Merck and Bayer AG. It is the most
effective, routinely used compound for treatment and control of schistosomiasis and
it is considered as the drug of choice for human schistosome. PZQ has very powerful
ability to lower the egg output, prevent liver fibrosis after early treatment with a
documented potential in reversing fibrosis in certain cases. Unfortunately, its
hydrophobicity, poor dissolution characteristics and high lipophilic nature resulted in
poor and variable bioavailability after oral administration. These together with the
recorded pre-systemic disposition are believed to be responsible for the reported low
cure rate which necessitates the repeated administration of high doses. Repeated
administration of large dose has been shown to contribute to the resistance of the
parasite to PZQ.
Many attempts have been done to overcome such drawbacks. This involved
co-administration of PZQ with inhibitors of hepatic microsomal enzymes such as
cimetidine or certain types of food. Other investigators presented some attempts to
improve the dissolution rate via complexation with cyclodextrins or solid dispersion
with polyvinyl pyrrolidone. Another research line devised implantable PZQ
formulation to prolong PZQ circulation time. Recent studies concentrated on new
drug delivery strategies to enhance the biopharmaceutical attributes of PZQ. These
included the utilization of liposomes, solid lipid nanoparticles (SLNs) and
nanostructured lipid carriers (NLCs).
Solid lipid nanoparticles (SLNs) can enhance the oral absorption of drugs but
its major drawback is reduced entrapment efficiency and drug loading owing to
possible expulsion of the lipophilic drug from the particle during chain crystallization
of the lipid on manufacturing. Introduction of liquid lipids as a component of lipid nanoparticles has been shown to overcome the poor entrapment efficiency with the
developed system being categorized as nanostructured lipid carriers (NLCs). NLCs
showed high potential for lipophilic drugs. It is important to note that variation of the
liquid lipid provided the investigators with a parameter which can manipulate and
enhance the drug delivery potential of NLCs as some of the lipid components can
contribute to enhanced membrane permeability. Manipulation of surface charge of
NLCs can affect the drug delivery potential and may influence the antibilharzial
activity of PZQ after loading in NLCs. This factor has not been investigated.