الفهرس 
CurcuminOnly 14 pages are availabe for public view
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Abstract
Curcumin is a well-known traditional medicine due to its anti-inflammatory and
antioxidant properties. Their pharmacological mechanisms of action and safety
have been thoroughly investigated in order to determine whether or not they
may be used in clinical and therapeutic approaches. Its limited water solubility
and quick metabolism, on the other hand, are major obstacles. Curcumin
limitations have been overcome using a variety of techniques using
nanotechnology-based approaches that have recently received attention.
Biopolymers such as gelatin and chitosan are playing a major role in
nanoformulations for drug delivery. This is due to their improved physical and
chemical properties and controlled drug release characteristics. Gelatin and
chitosan are used as drug delivery systems for a wide variety of drugs due to the
numerous advantages of both components, such as their high loading capacity
and the ability to release encapsulated drugs in a controlled manner. This study
is aimed at the production of curcumin-loaded gelatin and chitosan
nanoparticles and the investigation of their release properties.
Accordingly, this study aimed at was first prepare gelatin nanoparticles by the
nanoprcipetation method with different parameters such as emulsifier
concentration, gelatin concentration, crosslinker ratio, and the non-solvent
volume, to reach the optimal particle size with a uniform distribution.
On the other hand, chitosan nanoparticles were prepared with the aionic gelatin
method using Sodium Tripolyphosphate (TPP) to obtain finest nanoparticles.
After that, the swelling behavior of the both prepared nanoparticles was
examined.
In the second part, curcumin was loaded onto gelatin nanoparticles by an
emulsification linkage technique in the presence of SLES as an emulsifier, and
the encapsulation efficiency (EE) of the drug was controlled by the polymer
concentration, the emulsifier concentration, and the drug to polymer ratio, to
reach the higher encapsulation efficiency. As the same, curcumin was loaded
onto chitosan nanoparticles by ion crosslinking technique with TPP.
Transmission electron microscopy (TEM) confirmed the nanoparticles
homogeneous, well-defined morphology, and FT-IR characterized the potential
interactions between curcumin, gelatin, and chitosan. The drug entrapment
efficiency (EE) determined by the determination of the drug content in polymers
which carried out by an indirect method, by measuring the free drug (unloaded
drug).
The in vitro release behavior of free curcumin and curcumin drug loaded in
GNps and CSNps were evaluated in a buffer solution with pH 1.2 which
corresponds to the acidic medium of cancer cells or gastric fluid and pH 7.4
which refers the pH of the a blood buffer solution or intestinal fluid at 37 °C for
72 h. Finally the drug release data was obtained, quantitatively correlated and
interpreted with various mathematical models viz. the Zero order model, first
order model, Higuchi model, Hixson-Crowell model and Korsmeyer-Peppas
model and evaluated to understand the kinetics of drug release.
The morphology result showed that gelatin nanoparticles within the parameter
of different emulsifier concentrations have more definite and homogenous
particles with a small particle size of about 38 nm, especially in samples with
4% emulsifier concentration, which enables them to optimally entrap more
drugs. While chitosan nanoparticles showed very fine nano-sized particles with
2–5 nm. Furthermore, the swelling behavior of the nanoparticles was
determined at pH 1.2 and pH 7.4, which showed the nanoparticles are pH-
sensitive, where the swelling (%) increased with the increase in time, but the
nanoparticles showed increased swelling (%) at the more acidic pH 1.2 than at
pH 7.4. Also, the findings revealed that the optimum experimental condition in
curcumin loaded gelatin nanoparticles, which gave a higher EE of 82%, was a
combination of the set factor ideal levels. The best formulation combination had
a drug to polymer weight ratio of 20:200 (100 mg to 1000 mg), a gelatin
concentration of 10% (w/v) (1 g in 10 ml), and an emulsifier concentration of
2% (w/v), while curcumin was encapsulated in chitosan nanoparticles with 75%
EE. The release profile showed that free curcumin released was very rapid with
approximately 98% and 96% of the curcumin released in the media of PH (1.2)
and PH (7.4), respectively, compared with curcumin loaded in GNps, which
obtained 78% of the drug released after 72 hr in the acidic dissolution media.
On the other hand, the dissolution media of pH 7.4 showed a release percentage
of 60% after 72 hr. While the release performance of curcumin from CSNps
was more visible with a higher drug release percent, which reached 91% in 72
hrs in acidic media, compared with the release performance in alkaline pH 7.4
where the observed slow release pattern reached 64% in 72 hrs.
The results reveal that this study is promising for the use of GNps and CSNps as
sustained release drug delivery systems for cancer treatment due to the higher
amount of drug released at acidic pH 1.2, in which the acidic media of cancer
cells aids active release of the drug from GNps and CSNps, increasing drug
bioavailability in cancer cells and resulting in high therapeutic efficacy when
compared with normal cells.
Furthermore, by applying various mathematical models to drug release, the
most suitable model was based on the high degree of coefficient of correlation
of drug release profile from both nanoparticles. They were best fitted with the
Higuchi square root model, which follows Higuchi drug release kinetics, which
is diffusion controlled.