الفهرس 
REVIEW OF LITERATUREOnly 14 pages are availabe for public view
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Abstract
Infectious diseases represent a great risk as more than half of the
deaths happening worldwide. Brucellosis is one of the diseases that
caused by Brucella species, a bacterial pathogen.
Despite the profound success achieved by the usage of antibiotics
against infectious diseases, bacterial infections still conseder one the
greatest challenges the in global healthcare. In the last few years,
nanotechnology allows the development of new products that are used in
human medicine; for quick and specific drug delivery into cells and
tissues.
The present study was aimed at preparing and characterizeing the
nano- albumin particles and evaluateing thier safety on living
lymphocyte cell culture for their potential therapeutic as drug carrier to
enhance the treatment of brucella infection in male Balb.c mice.
The study was divided in to three parts, the first part aimed to
prepare the nano-albumin particles using the desolvation technique. Three
techniques were used for characterization of the prepared particles;
Transmission Electron Microscopy (TEM) was used to determine the
particles shape and size; Zeta Sizer to estimate the zeta potential of the
surface of the prepared nano particles and the size of this particles and
finally by using X Ray Diffraction (XRD) technique to assess the
chemical structure of the prepared nanoparticles. The second part aimed
to evaluate the safety of the prepared nano-albumin In Vitro by applying
MTT test for the cytotoxicity, comet test for genotoxicity and also study
of immune effect of this particles on living lymphocyte cells. Finally, the
third part amid to load two different types of antibiotics (Streptomycin
and Doxycycline) as combination therapy and (Gentamycin) as mono
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therapy on three different concentrations of the prepared nano-albumin
and to follow its efficiency to treat the intracellular Brucella infection.
This was by infecting male Balb/c mice intraperitoneally with 105 CFU of
B. melitensis 16M and divideding the mice into two groups, The first
group was diveded to six groups: negative group (received only saline),
positive gp. (infected with brucella without treatment), 3ed
gp.received
two doses of non loaded form (free form) of (180 µg Streptomycin and
36 µg Doxycycline) / mouse/ dose intraperitoneally, 4th, 5th and 6th
gps.
received the loaded form of (180 µg streptomycin and 36 µg
doxycycline) / mouse/ douse loaded on three different concentration of
nano-albumin (1mg/ml, 0.5 mg/ml, 0.25 mg/ml). As a combination
therapy, the second group also divided to six group: negative group
(received only saline), positive gp. (infected with brucella without
treatment), 3ed gp. received three doses of nonloaded form of 100µg
gentamycin / mouse/ dose and 4th, 5th and 6th gps received the loaded
form of 100µg Gentamycin / mouse/ dose on three different concentration
of nano- albumin (1mg/ml, 0.5 mg/ml, 0.25 mg/ml) as mono therapy,
three mice were sacarified after each dose and after 5 days of last dose in
combination therapy and after one week of last dose of mono therapy to
collect the spleen that used to follow the treatment by molecular study
using PCR and histopathology studies.
The prepared nano-albumin particles were nearly spherical in
shape and haveing smooth surface as determined by Transmission
Electron Microscopy (TEM). The sizes of the obtained nanoparticles
were 70 ± 10 nm with negative surface zeta potential. Additionally, the in
vitro safety of albumin nanoparticles has been demonstrated. Both
cytotoxicity and genotoxicity studies indicated that, there was no
observed toxic effect of nano-albumin on lymphocytes. Also, the results
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showed that the albumin nanoparticles enhances and promotes the
response of lymphocytes to PHA miotagen.
The produced nano- albumin particles could succefully interact
with streptomycin, doxaciclin and gentamicin to be used as a drug
delivary system.
Also the results showed that by using the different forms of
antibiotics (combination therapy and mono therapy) loaded on three
different concentrations of nano- albumin (1mg/ml, 0.5 mg/ml, 0.25
mg/ml ), the loaded form of the two types of therapy was more effective
in the treatment of the infection with B. melitensis than the non loaded
forms. The two concentrations (0.5 mg/ml and 0.25 mg/ml) were more
effective than the high concentration (1mg/ml) since the two low
concentrations cleared the infection totally (100%) but at the high
concentration it decreased the infection and the treatment in (S+D) to
66% and in (G) was 33%. Finally the combination therapy was more
effective than the mono therapy in the intracellular infection treatment.
In conclusion, the nano- albumin is easy to prepare, have no toxic
effect on living cells and it enhance the immune proliferation activity of
lymphocyts. Also it could successfully interact with different drugs.
So the of nano- albumin can be used as a carrier for antibiotic for
treatment of intracellular infection like Brucella. Further studies are also
required to confirm these preliminary results. Moreover, following up the
treatment efficiency for longer time are required.