بحث تخرج طالب من كلية الصيدلة حول النانوتكنولوجي

1. Nanotechnology-Applied Curcumin ForDifferent Diseases
Therapy
BY
Muhammad Hassan Abdul-Hussein Toman
Supervisor:
Prof. Dr. Abdul-Hussein Al-Jebory

2. ABSTRACT:
Curcumin, the main bioactive material of turmeric, has extensive
functional properties such as anti-diabetic, anti-inflammatory, anti-
cancer, and antioxidant activities. Nevertheless, curcumin exhibits some
main limitations including low water solubility, degradation during
processing or within the gastrointestinal tract and alkaline conditions,
leading to reduction of its bioavailability. For these reasons, many
attempts have tried to develop functionality of curcumin and overcome
its limitations through delivery systems, especially nanoencapsulation.
Nanoencapsulation.can deliver chemical stability, hydrophilicity,
sustained release and adequate dispersibility of curcumin in eventual
products (cosmetics ,food, and drug). Accordingly, the pharmacokinetic
properties of curcumin including biological half-life and bioavailability
can be enriched resulting in improved clinical and functional efficacy in
vivo

3. :
Introduction
Many investigators have worked on curcumin because to its
numerous therapeutic effects on varying diseases. Presently,
curcumin has received consideration mostly because of its anti-
inflammatory, antioxidant, antitumoral, apoptosis- inducing, and
antiangiogenesis effects, which were reported in many
examinations. The structural analogues of curcumin have been
stated to enhance the rate of absorption with a peak plasma half-
life. Current inquiries have considered curcumin a lead compound
for designing new chemotherapeutic agents for management of
cancers including colon cancers , prostate cancers , and other
conditions with indication of chemotherapy .

4. Current readings have discoursed poor bioavailability of curcumin
because of poor absorption, fast metabolism, and rapid systemic
removal. Nanotechnology is an evolving field that is potentially altering
the way we can manage ailments through drug delivery with curcumin.
The latest studies recognized several lines to improve the bioavailability,
to increase the plasma concentration, and to improve the cellular
permeability manners of curcumin. Numerous types of nanoparticles
have been found to be appropriate for the encapsulation or loading of
curcumin to enhance its therapeutic effects in different ailments.
Nanoparticles such as polymeric nanoparticles, liposomes, micelles,
nanogels, niosomes, dendrimers, silvers, cyclodextrins, and solid lipids
are emerging as one of the valuable alternatives that have been shown to
deliver therapeutic concentrations of curcumin.

5. NANOTECHNOLOGY
APPROACHES FOR CURCUMIN:
Nanoparticles gained huge popularity in the last decade due to
their potential to increase the therapeutic effects of the
encapsulated drugs by protecting drugs from enzymatic
degradation, providing their controlled release and extended blood
circulation, changing their pharmacokinetics, decreasing their
toxicity, and limiting their nonspecific uptake

6. Liposomes
Liposomes are artificial vesicles with globular character which
can be formed from natural phospholipids. They are self-
assembling closed colloidal structures formed of lipid bilayers,
and they have a spherical form in which an outer lipid bilayer
surrounds a central aqueous space. They are specified to act as
immunological adjuvants and drug carriers.
In this regard, to improve the solubility of curcumin, Rahman et
al. formed -cyclodextrin-curcumin inclusion complexes that
entrapped both native curcumin and the complexes distinctly into
liposomes. All curcumin-containing formulations were effective
in reducing cell proliferation.

7. Micelles
A classic micelle is a surfactant molecule aggregate dispersed in a liquid
colloid. It is a nanosized vesicular membrane that soluble in water.
Micelles are lipid molecules that organize themselves in a spherical
shape in aqueous solutions with a very narrow range from 10 to 100 nm
in size, which makes them more stable toward dilution in biological
fluids.
Niosomes
Niosomes are microscopic lamellar structures of nonionic surfactant of
alkyl or dialkyl polyglycerol ether group with cholesterol that were first
introduced in the 70s. Niosomes can provide a vessel for drug molecules
with a wide range of solubilities owing to presence of hydrophilic,
amphiphilic, and lipophilic moieties in the constitution.

8. Cyclodextrins
Cyclodextrins (Cds) are a family of complexes formed from sugar
molecules bound together in cyclic oligosaccharides. They are
formed from starch by using enzymatic switch. Cds are cyclic
oligomers of glucose that can form water-soluble inclusion
complexes with small molecules and portions of large
complexes.They have an interior hydrophobic surface which can
offer a place for residence of poorly water-soluble molecules,
whereas the external hydrophilic area makes its solubility possible
in the aqueous setting with high stability.

9. Dendrimers
Dendrimers are a group of significantly branched globular
polymers that are made with structural control rivaling traditional
biomolecules. Dendrimers are a series of polymeric architectures
with different chemical and surface-related properties. This
nanospace represents an isolated environment, thus reducing
toxicity associated with the payload. The well-defined
organization, dense spherical form, size, monodispersity, and
controllable “surface” functionalities of dendrimers make them
excellent candidates for assessment as drug delivery services.

10. Nanogels
Nanogels are self-possessed of cross-linked three-dimensional
polymer chain networks which are produced by covalent linkages
and can be modified to gel networks with biocompatible and
degradable properties. The porosity among these cross-linked
networks not only provides a good reservoir for loading drugs but
also retains them from environmental degradation.
Moreover, nanogels can be chemically reformed to incorporate
several ligands for targeted drug transfer, triggered drug release,
or preparation of composite materials.

11. •
Chitosans
Chitosan is a linear polysaccharide formed of randomly disseminated
deacetylated and acetylated units.
Gold Nanoparticlee
Metal nanoparticles have been recognized since very ancient times, and
gold nanoparticles (AuNPs) with optical and electrochemical uniqueness
have proven to be a potent apparatus in nanomedicinal requests . They
have also been largely used in immunochemistry,
immunohistochemistry, and immunoblotting for electron microscopy.
Silvers
Silver has been used as a very effective material for antimicrobial
efficacy. In small concentrations, it is safe for human cells but fatal for
the majority of bacteria and viruses.

12. CLINICAL IMPORTANCE OF
CURCUMIN NANOPARTICLES:
Anticancer activity: Cancer is the most wide spreading
disturbing disease diagnosed around the world. Predictable
managements like chemotherapy, radiation therapy and surgery
cause adverse side effects. Hence, it is important to develop safer
and unusual treatment technique to cure this malignant illness…
cancer such as breast,prostate, pancreatic, oral, skin, ovary, etc..
Lately, curcumin nanoformulations with improved bioavailability,
solubility and specific tumour cell targetting were used as novel
therapy for cancer.

13. Antimicrobial activity: Traditionally, turmeric has been used as
an antimicrobial agent. Curcumin nanoparticles were used as they
are identified to possess superior antimicrobial activity than the
normal curcumin.

14. Anti-HIV activity: Human immunodeficiency virus (HIV) attacks the
immune system by destructing CD4+ T cells. The progressive failure of
the immunity finally leads to acquired immunodeficiency syndrome
(AIDS). The CD4+ T cells are a type of white blood cells that defend the
body from infections. The antiretroviral drug supresses the virus, but the
complete removal was not yet achieved. Hence, it is important to
improve an alternative therapy to manage this lethal condition. Gandapu
et al., stated that curcumin-loaded apotransferrin nanoparticles prepared
by sol-oil technique was very effective to prevent HIV-1 replication by
transferrin mediated endocytosis. Ordinarily, HIV-infected cells express
transferrin receptors. Curcumin-loaded apotransferrin nanoparticles bind
specifically to the receptor and carry the drug in to the infected cell.
Steadily, the drug is released out and the viral cDNA synthesis is
obstructed leading to the end of HIV-1 replication.

15. Antimalarial activity: Malaria is caused by parasites and carried
by female Anopheles mosquitoes. The in vivo readings of
curcumin-loaded hydrogel nanoparticles stated by Dandekar et al.,
showed antimalarial activity. The toxicity readings showed the
oral safety and cytotoxic effects of the nanoformulations.

16. Anti-inflammatory activity: In antique Indian medication,
turmeric has been used as an anti-inflammatory agent. Curcumin
delivered by exosome proved more stability, target specificity and
they were found in high concentrations in blood [66].

17. Alzheimer’s disease (AD) : Is a progressive neurodegenerative
disorder that occurs around the world. It is a common form of
dementia associated with memory loss and gradual death of brain
cells. The neuronal death occurs due to the accumulation of beta-
amyloid plaques and activation of caspase pathway. PLGA-coated
curcumin nanoparticles in conjugation with Tet-1 peptide possess
anti-amyloid and antioxidant property and it can be used as a
possible drug for treating AD.The curcumin-encapsulated PLGA
nanoparticles stimulated neural stem cell proliferation and
neurogenesis in the hippocampus and subventricular zone of
grown-up rats by stimulating the Wnt/β-catenin pathway. Thus,
employing nanocurcumin proved to be a better therapeutic
approach for the treatment of AD.

18. Conclusion:
Nanotechnology-costructed drug transport system overcomes the limits of
the conventional management approaches. In this research, the therapeutic
applications of curcumin nanoparticles were discoursed. Curcumin
nanoparticles revealed greater stability, bioavailability, target specificity,
controlled particle size and sustained drug release. Curcumin was used in
variable nanoforms like nanoemulsion, polymeric nanoparticles, polymeric
micelles, etc. These nanoparticles work as a potential agent against different
ailments like cancer, microbial infection, AIDS, malaria, AD and
inflammatory diseases. To increase the efficacy of the drug, inquiry should
be dedicated on targetting the infected cells and controlled drug release
without toxicity. In the future, more pre-clinical and clinical investigations
must to be directed to define the hidden potentials of nanocurcumin in the
field of pharmaceutical sciences and medicine.
•