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العنوان
Studies on Innovative Systems Based on Nano-Sized Carbohydrate Polymer/Metal Nanoparticles and their Applications in Medical and Other Purposes /
المؤلف
El-Naggar, Mehrez El-Sayed El-Sayed.
هيئة الاعداد
باحث / Mehrez El-Sayed El-Sayed El-Naggar
مشرف / Abd El-Gawad M. Rabia
مشرف / Ali Ali Hebeish
مناقش / Mohammed H. El-Rafie
مناقش / Manal A. El-sheikh
مناقش / Hamed Ahmed Derbala
تاريخ النشر
2014.
عدد الصفحات
435 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
Organic Chemistry
تاريخ الإجازة
1/1/2014
مكان الإجازة
جامعة عين شمس - كلية العلوم - Organic Chemistry
الفهرس
Only 14 pages are availabe for public view

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from 435

Abstract

The candidates own work aims at creation of innovative systems
for application in medical domains notably drug delivery and wound
healing. Such systems are based on nano-sized carbohydrate polymer.
For convenience the work is divided into six chapters dealing with the
preparation, characterization and utilization of these systems in medical
domains are summarized under.
Chapter 1: Ultra-Microstructural features of perborate
oxidized starch
Oxidation of native maize starch (NS) using Sodium perborate at
these different concentrations yields three levels of oxidized starches.
The latter include low-, medium-, and highly oxidized starches;
nominated as LOS, MOS and HOS respectively. The ultrafine
structures of these oxidized starches along with native starch were
monitored using world - class facilities. Results obtained bring into
focus conclusions given under:
(a) The FT-IR and X-ray diffraction patterns indicate the creation of
carbonyl groups and a decrease in the crystalinity shape of starch
during oxidation; in accordance with the results of carbonyl and
carboxyl groups obtained through chemical analysis. b) The oxidized starches display increased solubility and decreased
apparent viscosity – vis-à-vis - native starch upon increasing the
extent of oxidation.
(c) The resultant oxidized starches have greater uniformity, display
greater thermal stability than the native maize starch, and follows the
order: HOS > MOS > LOS > NS when all these substrates are
subjected to thermal gravimetric analysis.
(d) High-resolution scanning electron microscopy clarify that the
surfaces of oxidized starches became rough and the edges lost
completely their definiteness upon oxidation.
(e) The marginal amount of the residual components of SPB after
repeated washing in the resultant HOS powder was found.
The above ultra-microstructural features of oxidized starches
brought about by treating native maize starch with sodium perborate
advocate their use in different applications. Of these, we have indeed
used with great success the perborate- oxidized starches in textile warp
sizing on industrial scale. Their use in the medical domains is in
progress. Chapter 2: Ultra-fine characteristics of Starch
Nanoparticles Prepared Using Native Starch and Oxidized
Starches With and Without Surfactant
Current work addressed two main objectives. The first was to
establish a simple and reproducible method for synthesis of starch
nanoparticles. This objective could be fulfilled through modification of
the nanoprecipitation method by using alkaline aqueous solution as the
solvent and ethanol as precipitant; ethanol was added drop-wise to the
starch paste solution. The second objective was to verify differences in
ultrafine characteristics of St-NPs prepared using native starch vis-à-vis
those obtained using low, medium and high oxidized starches using
world class facilities. Main conclusions arrived from these investigation
are given below.
1. TEM, particle size analyzer and polydispersity index (PDI)
confirmed the successful synthesis of spherical starch nanoparticles
within the range 135-155 nm with PDI value 0.333 before the
addition of surfactant (Tween® 80).
2. FT-IR and X-ray diffractograms provide evidence that the chemical
structure of Starch nanoparticles have the same structure of the
unmodified native starch. 3. TGA reveals that, the thermal stability of starch nanoparticles are
higher than native starch. Furthermore, the surface charge of starch
nanoparticles are higher than the native starch but still have low
stability.
4. The optimum conditions for preparation of starch nanoparticles was
5 g NS, along with 30% NaOH (OWS), total volume 100 ml H2O;
100 ml absolute ethanol, Temperature 25C.
5. After the addition of 20 % Tween® 80 (OWS) before precipitation
the particle size decreases dramatically to reach a value 103 nm
which still in good dispersion.
6. The FT-IR and XRD of starch nanoparticles coated with and without
Tween® 80 have the same function groups without any minor shift
in the wavelength indicating that there is no chemical reaction
between starch and the surfactant.
7. The particle size evaluated for the three oxidized starches
nanoparticles by DLS and TEM significantly decreased following
the order HOSt-NPs < MOSt-NPs < LOSt-NPs.
8. The particle size of highly oxidized starch nanoparticles has the
smallest size and reaches 22 nm with good polydispersity. 9. The stability of highly oxidized starch is higher than that of starch
nanoparticles, in conformation with zeta potential.
It is expected that, these native and oxidized starches in
the nanoform will have potential applications in medical domains,
particularly for drug carrier.
Chapter 3: Development of new system based on
crosslinked starch nanoparticles for diclofenac sodium
delivery
Current work presents a manifold study aiming at development
of a promising and controlled release transdermal delivery system to
enhance the therapeutic efficiency of diclofenac sodium (DS). The
system is based on crosslinked starch nanoparticles which were
synthesized using native starch (NS) and oxidized starches derived
thereof. The oxidized starches comprised low, medium and highly
oxidized starches that could be abbreviated as LOS, MOS and HOS,
respectively. Crosslinking was effected by reacting sodium
tripolyphosphate (TPP) at different concentrations. Crosslinked starch
nanoparticles loaded with DS were synthesized according to the
nanoprecipitation method using different DS concentrations.
A two-level factorial design were practiced for prediction of
optimized formulation for DS loaded crosslinked starch nanoparticles. At this end, the optimized formulation was applied to LOS, MOS and
HOS. The formulated nanospheres were systematically studied by
monitoring drug loading, entrapment efficiency, transmission electron
microscopy (TEM), particle size analyzer, polydispersity index (PDI)
and zeta potential for shape and surface characteristics and in vitro
release studies. Physicochemical characterization and analysis of the
formulated nanosphares were also excercized using fourier transform
infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and
Differential scanning caliorimetry (DSC) to determine the fine physical
nature (crystallinity), thermal behaviour and possible occurrence of
interaction between DS and the crosslinked starch nanoparticles.
Interaction of crosslinked starch nanoparticles with DS causes profound
changes in the crystalline structure of DS; DS is completely converted
to amorphous structure. Application of experimental In vivo targeting
efficiency of the optimum formula of crosslinked nanoparticles of NS,
LOS, MOS and HOS with TPP and loaded with DS were examined
histopathologically in skin irritation of healthy rats.
Obviously, then, the essential target of the work could be
successfully achieved. Application of experimental design allowed the
optimization of different factors to yield spherical nanoparticles with
small particle size, low polydispersity index and high entrapment efficiency and sustained release for DS drug. The histophathological
studies on rat skin advocate the use of the designed transdermal DS
loaded crosslinked starch and medium oxidized starch nanoparticles
formulations as they are safe and non-irritant to rat skin. This would
render the designed formulation a safe, highly effective, controlled and
convenient mean of therapy with the non-steroidal anti-inflammatory
drug (NSAIDs).
Chapter 4: New Formulation of Indomethacin and
Acyclovir Based on Crosslinked Starch Nanoparticles for
Controlled Drug Delivery
Polymeric nanoparticles which posess a better reproducibility
and stability profile than other carrier like microparticles have been
studied as alternative drug carrier. An eco-friendly nanoprecipitation
technique was put forward to synthesize native and oxidized starches
nanoparticles loaded with insoluble drugs such as Indomethacin (IND)
and Acyclovir (ACV) nanoparticles were also loaded onto crosslinked
starch nanoparticles. Factors studied to find out the optimum conditions
were selected through factorial design for preparation of different
formulations of crosslinked starch nanoparticles. Major parameters
studied 20 mg, 50mg drug concentration and 0.5, 1g TPP Concentration
while the concentration of starch and surfactant were kept constant. World-class facilities were used for evaluation as in the case of
diclofenac sodium. The results obtained indicated that (a) the best
formula for IND loaded starch nanoparticles with small spherical size
and PDI, high zeta potential, high entrapment efficiency and controlled
release was at 0.5 g TPP and 20 mg IND. On the other hand, the best
formula for ACV loaded starch nanoparticles was at o.5 g TPP and 50
mg ACV. (b) FT-IR, XRD and DSC indicated that there is no chemical
interaction between crosslinked starch nanoparticles and drug (IND or
ACV). (c) Entrapment efficiency and in vitro release of drugs from
crosslinked starch nanoparticles followed the order: Native> Low
oxidized> Medium oxidized> highly oxidized starch. The results
obtained could be attributed to the dependence of the in vitro release
rate of IND and ACV on the viscosity of starch and oxidized starches
when native starch have higher holding capacity and entrapment
efficiency for loading the drugs under investigation.
Chapter 5: Nanostructural features of silver
nanoparticles powder synthesized through concurrent
formation of the nano-sized particles of both starch and
silver
For the first time, powdered starch-silver nanoparticles were
synthesized having highly concentrated AgNPs with extremely small
sizes by using modified nano-precipitation method. In particular, we describe an environment friendly one-step method to synthesize
powdered AgNPs. This was done by reduction of AgNO3 solution using
alkali dissolved starch meanwhile the latter acted as stabilizing agent
for the formed AgNPs. Ultimately, the AgNPs in the colloidal solution
were coated with starch were precipitated using the least amount of
ethyl alcohol as precipitating agent. This green approach may find
various medicinal applications (e.g. wound healing) as well as
technological applications.
Chapter 6: More Insight on characterization of Nanosized
Particles of Silver Powder and their Application in
Antimicrobial Wound Dressing and Anti-inflammatory
Efficacy
Powdered silver nanoparticles and highly concentrated solutions
of AgNPs using alkali dissolved starch which act the dual role: as
reduction for Ag+ and stabilizer for AgNPs formed thereof. AgNPs
colloidal solution having different concentrations (60, 125 and 250
ppm) was prepared from stock solution having highly concentration
30000 ppm AgNPs. The AgNPs colloidal solutions were used for
treatment of cotton fabrics as per the pad-dry-cure technique. Cotton
fabrics loaded with these three different concentrations of AgNPs
colloidal solutions were evaluated for various medical applications, namely, antimicrobial, wound healing, anti-inflammatory as well as
toxicity. The antimicrobial efficacy of dressing containing 250 ppm
AgNPs was more effective against microorganisms including bacteria
and fungi than that of dressing containing 60 and 125 ppm as indicated
by the inhibition zone. The wound healing of dressing containing the
highest content of AgNPs (250 ppm) acquire the greatest potent healing
which is nearly similar to the controlled cream (Dermazin). It was also
found that wound healing is intimately linked to inflammation in
normal circumstances as various inflammatory mediators are secreted to
modulate the healing process within wounds. The obedema percent of
250 ppm AgNPs was nearly the same as appeared in the case of
standard drug (indomethacin). The safety of AgNPs on subsequent
experiments should be kept at or below 10 μg/mL. The antimicrobial
wound dressing of AgNPs treated cotton fabrics is proposed to have
promising potential in smart textiles, medical purposes as well as in
various biological fields.