3. INTRODUCTION
Cancer Treatment:
Cancer has proved itself to be one of the most detrimental and largely
spreading disease in the world.
Anticancer drugs lack the ability to distinguish between malignant cells and
healthy cells, which causes severe side-effects.
Instead, Drug delivery systems with different stimulating factors (such as pH
response) are used. Cancer cells has pH (5.7-7), which is lower than blood
and healthy tissue.
Gastric cancer, one of the most common type of cancer, is caused by a
bacteria called Helicobacter pylori (H. pylori), which colonizes in stomach.
H. pylori inhibits autophagy, body’s natural process to eliminate toxic
materials from cells.
Autophagy regulating drug is loaded on suitable nanoparticles to enhance the
efficacy.
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4. INTRODUCTION
Why Nanoscience is chosen?
Nanotechnology has the potential in not only drug delivery but also
diagnosis, prevention and treatment for different diseases.
Creation of doxorubicin-loaded liposomes for the treatment of breast
cancer in the year 1960 is marked as the beginning of nanoparticle
based cancer therapy.
Nanomedicine is considered to be an emerging alternative for
controlled and targeted drug release due to its bioavailability, proper
targeting and non-toxic behavior.
Due to its significantly large surface-to-volume ratio, nanoparticles
can be an effective vehicle for controlled release of drug.
Efficacy of the particles can be increased by regulating different
parameters during the synthesis process.
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5. CALCIUM CARBONATE AS CARRIER
Aluminum Hydroxide, Magnesium Hydroxide based antacids are usually
used for the treatment of gastric related issues, such as acid burns,
indigestion, stomach ache as well as severe diseases, like peptic ulcer,
gastritis, hernia, hyperacidity.
Excess usage of magnesium causes diarrhea and in the long run, can cause
severe kidney problems. Aluminum can affect the calcium of our body which
results in osteoporosis if taken for long term.
As an alternative, Calcium Carbonate is considered as the nanocarrier.
It has a unique non-toxic behavior along with its biocompatibility,
biodegradability, and specifically pH sensitivity.
Due to the slow degradation of CaCO3 nanoparticles, they can be used as
controlled drug release systems to retain drugs in cancer tissues for longer
times after administration.
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6. LITERATURE REVIEW
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References Overview Remarks
Layer-by-layer coated calcium carbonate
nanoparticles for targeting breast cancer
cells
https://doi.org/10.1016/j.bioadv.2023.213563
Synthesis of homogeneous CCNP (coated with
Heparin and Ethylene glycol) with the encapsulation
of Rhodamine (not tested with any particular drug).
Surface modification is done by LBL method using
ligand receptor Hyaluronic Acid (HA).
The LBL coating helps to discriminate between
healthy and cancer tissues, and the release
response is good for EG coated CC NP. Particle
size ~400nm. HA-NPs have accumulation at the
site of infection compared to water soluble HA
derivatives.
Co-delivery of gemcitabine and Triapine
by calcium carbonate nanoparticles
against chemoresistant pancreatic cancer
https://doi.org/10.1016/j.ijpharm.2023.122844
Synthesis of CC NP with Triapine and GEM coating.
Triapine is used to suppress the GEM resistance of
cancer cells. The efficacy of the particles are tested
using 2D PANC-1/GEM cells and 3D tumor
spheroids.
Coated CC NP shows inhibition of formation and
growth of cancer cells. But, initial Zeta potential
is observed to be increased after Triapine and
GEM coating, which reduces the particle stability.
The particle sizes ~115nm.
Encapsulation of anticancer drug cisplatin
in vaterite polymorph of calcium
carbonate nanoparticles for targeted
delivery and slow release
https://doi.org/10.1002/cplu.201500515
Synthesis of porous vaterite CCNP using Ethylene
Glycol for cancer treatment. The particles are loaded
with anticancer drug cisplatin.
Thermodynamically unstable vaterite CCNP
was synthesized. pH response of the loaded
particles in acidic environment satisfactory
enough. Particle size ~20-80nm, with avg pore
size 10-100 nm.
Synthesis of CoFe2O4-CaCO3
nanocomposite for simultaneous magnetic
hyperthermia and drug release
applications
https://doi.org/10.1016/j.jallcom.2023.170636
Synthesis of nanostructures using sol-gel-auto-
combustion method. The synthesized particles are
encapsulated by CaCO3 polymorphs. The
nanocomposites are tested for hyperthermia and drug
release.
Particle size ~50-150nm. By increasing the
amount of CaCO3, cell viability of enhanced.
Saturation magnetization is reduced with
increasing CaCO3.
7. CRITICAL ANALYSIS OF
LITERATURE REVIEW
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1. Smaller particles can be synthesized to enhance loading capacity, so
that less amount to substance will be sufficient for cancer treatment.
2. Low zeta potential is essential to attain colloidal stability. Surface
modification of particles tends to show misleading Zeta values.
Appropriate surface modification procedure has to be identified to
stabilize the particles better.
3. Since it is difficult to control its nucleation and growth, vaterite tends
to transform into calcite even at room temperature. Calcite is the most
stable polymorph of calcium carbonate crystal, which makes it suitable
as a drug delivery system.
4. Surface modified Calcium Carbonate nanoparticles can be
characterized for its efficiency in gastric cancer treatment.
8. OBJECTIVES
Synthesis of calcium carbonate nanoparticles, preferably in less than
50nm size range.
Search for a surface modification suitable for gastric cancer
treatment.
Loading the Drug and measure the efficacy of the loaded particles.
Characterize the synthesized particles for biomedical applications.
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9. EXPERIMENTAL PROCEDURE
Surface modification:
Chitosan is coated to regulate the blood circulation through
infected cells.
Sodium alginate is used for encapsulation.
Folate conjugation is done for folate receptors of gastric cancer
infected cells.
Drug loading:
Drug is loaded on the nanoparticles at 1:1 ratio, with DI water as
the solvent.
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Na2CO3+ DW
CaCl2+ DW
Soluble Starch
used the surfactant 1. Stirred
overnight
2. Centrifuged
3. Dried overnight
4. CCNP
powder
10. 1 0
Low zeta potential value is necessary
for ensuring colloidal stability of the
particles.
Initial zeta value for uncoated CCNP
is not satisfactory enough, thus
surface modification has been
required.
After folate conjugation, the zeta
potential is observed to have
decreased significantly.
Smaller particle size contributes in
avoiding agglomeration and
inaccurate zeta value.
Fig: Change In Zeta Potential For Different Layers
11. LOADING CAPACITY AND EFFICIENCY:
1 0.60552
0.5 0.5851
0.25 0.57301
0.125 0.55565
0.0625 0.54656
0.03125 0.54417
0.01562 0.54575
0.0078 0.54695
• The absorbances mentioned above are corresponding
to the wavelength = 350nm
• For drug loaded CCNP, absorbance= 0.5799
• So, the calculated concentration is= .51675mg/ml
• Calculated Loading efficiency[loaded drug/total
drug] = 89.66%
• Calculated loading capacity[loaded drug/total
particle] = 89.66%
Fig: Calibration curve for Glycyrrhizin
Sodium alginate is natural polymer , which can be used for encapsulation as it enhances the biodegradability, and biocompatibility of the particles. It can also increase bioavailability(being available to the full extend where it is intended to be administered.) chitosan coating with sodium alginate is a good encapsulation for protein based drugs.
Zeta potential- electric potential at the slipping surface(surface which differentiates between mobile fluid and fluid that is attached to the particle surface.) magnitude of zeta potential indicates stability, as it will confer the repulsive force between two adjacent similar particles in a dispersion. For smaller particles, high negative value of zeta means higher stability, that means repulsive force is high enough that it will resist agglomeration.
Colloid- one phase or substance dispersed in another.- homogeneous mixture of two or more substances, not stable.
stability=1. kinetic 2. thermos 3. electrostatic 4. steric