curcumin loaded nanocapsules to improve the bioavailability of curcumin

1. CURCUMIN
LOADED
NANOCAPSULES
Presented by,
Thamrook s
Mpharm
Pharmaceutics
ECPS
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2. What is curcumin?
•Curcumin is the yellow color pigment obtained from the powdered rhizome of
Curcuma longa (Zingiberaceae), has numerous biological activities, such as
anti-inflammatory, antiproliferative, antioxidant, and chemopreventive
activities.
•The medicinal applications of curcumin are limited by its poor solubility and
low oral bioavailability.
•Due to its low rate of absorption and poor water solubility, curcumin is often
formulated into specially designed carriers such as nanoemulsions,
nanosuspensions, nanotubes, and liposomes.
•Recently, chitosan nanoparticles have been studied as carrier materials of
bioactive ingredients due to their high mucoadhesive capacity and safety .
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3. •Chitosan is a deacetylated derivative of chitin composed of (1,4)-2-
amino-2-deoxy-D-glucopyranose units and a small amount of N-acetyl-D-
glucosamine residue.
•It has excellent biodegradability, biocompatibility, low toxicity, and
mucoadhesivity.
•Chitosan nanoparticles of curcumin is prepared by ionotropic gelation.
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4. Ionotropic gelation method
•Among the various methods to produce chitosan nanoparticles ionotropic
gelation is a commonly described method in which an initiator is added to an
aqueous chitosan solution.
•Chitosan has the ability to crosslink in the presence of counter ions to form
hydrogels. Several molecules can be used as ionic crosslinkers.
•Ionic compounds such as sodium sulfate, inorganic phosphate salts, or
tripolyphosphate interact with chitosan through electrostatic interactions Thus,
nanoparticles can be prepared using tripolyphosphate and chitosan.
•This technology allows for the production of nanocapsules with high
encapsulation efficacy, the use of nontoxic reagents to protect the active
compounds, easy scale-up to an industrial level procedure, and the ability to
reach organs such as the brain.
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5. Preparation of curcumin nanocapsules
•CLNCs were prepared by a modified method involving chitosan cross-
linking on the surface of emulsion drops.
•The oil phase was prepared by first mixing curcumin powder (1.5 % w/w)
into a blend of surfactants (31.5 % w/w of a mixture of Tween 80/Span 80 in a
2 : 1 mass ratio), 52.5 % w/w liquid paraffin and 14.6 % w/w of ethanol.
•After stirring, the tube was heated to 50 °C during 30 min and gently stirred
overnight at room temperature. Once the curcumin was dissolved in the oil
phase, this phase was used to produce an emulsion using a film spinning
apparatus.
•The aqueous phase (77.8 % w/w of water) was placed into the deviceʼs
vessel and then the oil phase (22.2 % w/w) was added during vessel spinning.
Once the curcumin emulsion was formed, it was mixed with a SDS solution
(1 % w/w of SDS in water) in an equal volumetric proportion.
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6. •The emulsion/SDS solution mixture was added dropwise to an excess of
chitosan solution consisting of 1 % w/w of chitosan dissolved in 1 % v/v
aqueous AA while stirring at 600 rpm.
•Then, the obtained CLNCs were collected by centrifugation (10 000 × g
for 10 min, 25 °C) and washed with distilled water.
•Three different molecular weight and deacetylation degree chitosan
polymers were used in the formulation in order to prepare curcumin-loaded
nanocapsules (mass ratio 1 : 1.4).
•Chitosan-Si(300000), Chitosan-Ab(400000), and Chitosan- Bi(710000).(mw
in dalton).
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7. Nanocapsules characterization
•Particle size and distribution
Nanotrac TM 150 instrument (Microtrac) to determine the average particle
size and distribution of CLNC. The equipment measuring principle is DLS
using a laser diode of 780 nm.
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8. Transmission electron microscope
•Hitachi H-7700 instrument to obtain TEM pictures of the CLNCs. The
particles were suspended in distilled water and the dispersion was placed on a
metallic plate and dried at room temperature.
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9. Entrapment efficacy
•Twenty mL of CLNC suspension was separated by centrifugation (10 000 ×
g for 10 min, 25 °C). After centrifugation, the pellet was collected and
suspended into 5 mL of methanol.
•This suspension was sonicated for 5 min to disaggregate the pellet and
pierce the chitosan layer, forcing the release of the curcumin. The amount of
released drug was measured by HPLC. The EE was calculated using the
following equation:
Where,
m0 is the total mass of added curcumin
m is the experimental mass of curcumin loaded into the CLNC.
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11. in vitro curcumin release profile
•5 mL of the latter (0.16 mg/mL curcumin) were suspended in 25 mL of two
release medias, either simulated gastric fluid or simulated intestinal fluid. The
suspensions were placed into a temperature-controlled bath (37 °C) and
stirred at 400 rpm.
•At designated time intervals, 1 mL of sample was withdrawn; the lost
volume was replaced with the corresponding release medium to maintain the
volume of the solution .
•To separate the particle from the medium, the collected samples were
centrifuged (13 000 × g for 15 min) and filtrated (0.1 µm pore filter). The
rate of delivery of curcumin was analyzed by HPLC.
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13. Animal study (invivo)
•Male Swiss mice (20–22 g) were kept at 24 ± 1 °C and with free access
to food and water. Mice were randomly divided into two groups. One group
of mice received a saline solution and CLNCs (5 mg/kg curcumin)
intravenously via the tail vein.
•Another group was given CLNCs orally (25 mg/kg), an oil-free curcumin
solution (25 mg/kg), and a saline solution. The animals had access to water
and food after dosage administration.
•Blood (1 mL) and tissues samples (brain and heart) were collected in
heparinized tubes at 0, 2, 5, 10, 30 min,1 and 12 h after intravenous
administration or at 10, 20, 30, 45 min, 1, 2, and 12 h after oral
administration (5 mice were used for each point).
• The tissue was collected into separate containers and the plasma was
separated from the heparinized blood by centrifugation and storage at 20°C
prior to analysis.
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15. CONCLUSION
• The best results were achieved using chitosan-Bi with a molecular weight of
710 000 Da. A bimodal distribution was observed in samples; moreover,
chitosan-Bi produced the lowest particle size (197 nm).
•The entrapment efficacy of all chitosan nanocapsules produced reached values
between 75 and 92 %. Their rate of drug release at different pH levels (2.0 and
7.4) showed a fast onset of curcumin release.
•Also the in vivo results(chitosan-Bi) showed that the oral bioavailability of
curcumin from these nanocapsules is higher than that of normal curcumin.
•These nanocapsules have the ability to cross the blood-brain barrier, and its
production is an easy to scale-up procedure using nontoxic materials
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