1) Nanoparticles between 1-100 nanometers can be used for targeted drug delivery by encapsulating drugs in their cores and functionalizing their shells with targeting agents.
2) Core-shell nanoparticles in particular consist of a functional core, modifiable shell, and surface biomolecules. They are useful for drug delivery because the core encapsulates drugs while the shell can be targeted to specific cells.
3) One example are PLGA-lecithin-PEG core-shell nanoparticles developed for controlled drug release. The hydrophobic PLGA core encapsulates chemotherapeutics while the lecithin-PEG shell provides stability, targeting, and prolonged circulation.
1. Use of Core-Shell Nanoparticles in
Drug Delivery
Submitted by:
Nikita Gupta
01140801014
M.Tech NST
2nd semester
2. Introduction
Nanoparticles : any particle that is sized between 1 and 100
nanometers (in terms of diameter). The use of nanoparticles
allows one to change the pharmacokinetic properties of the drug
without changing the active compound.
General properties of nanoscale particles:
1. High surface area to volume ratio.
2. Able to interact with biomolecules on the surface of cells
3. Able to diffuse through the body well.
3. Introduction
Drug is a chemical substance used in the treatment,
cure, prevention, or diagnosis of disease or used to
enhance physical or mental well-being.
Drug Delivery delivering the drug at the right place, at
the right concentration for the right period of time.
Because of their small sizes, nanoparticles are taken by
cells where large particles would be excluded or cleared
from the body. Nanoparticles for drug delivery can be
metal-, polymer-, or lipid-based.
4. Types of Drug Delivery
TARGETED DRUG DELIVERY:
Delivering a drug to a specific site in the body where
it has the greatest effect, instead of allowing it
to diffuse to various sites, where it
may cause damage or trigger side effects.
CONTROLLED DRUG DELIVERY:
Is one which delivers the drug at a predetermined
rate , for locally or systematically , for specified
period of time .
5. Nano shells - An Introduction
Developed by Drs. Naomi Halas and Jennifer West – Rice University 1994
Nano shells have a core of silica and a metallic outer layer. These
nanoshells can be injected safely.
Because of their size, nanoshells will preferentially concentrate in cancer
lesion sites. This physical selectivity occurs through a phenomenon called
enhanced permeation retention (EPR).
The Nano shells carry molecular conjugates to the antigens that are
expressed on the cancer cells themselves or in the tumor
microenvironment. This second degree of specificity preferentially links
the nanoshells to the tumor and not to neighboring healthy cells.
The most useful Nano shells are those that absorb near infrared
light(700nm-1mm) that can easily penetrate Several centimeters in human
tissues.
Absorption of light by Nano shells creates an intense heat that is lethal to
cells.
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6. Generally speaking,
biocompatible core–shell
nanoparticles are composed of
a functionalized core, a
modifiable shell, and the
biomolecules modified on the
surface of the nanoparticles as
shown in Figure. The three
parts all make prominent
contributions to their
application of biomedicine.
7. Different Shaped Core/shell Nanoparticles
Figure: Different core/shell nanoparticles:
(a) spherical core/shell nanoparticles;
(b) hexagonal core/shell nanoparticles;
(c) multiple small core materials coated by single
shell material;
(d) nanomatryushka(Nano sphere in a shell) material;
(e) movable core within hollow shell material.
The properties of nanoparticles are not only size
dependent but are also linked with the actual shape.
For example, certain properties of magnetic
nanocrystals such as the blocking temperature,
magnetic saturation, and permanent magnetization are
all dependent on particle size, but the coercivity of the
nanocrystals totally depends on the particle shape
because of surface anisotropy effects
Other nanoparticle physical and chemical
properties such as catalytic activity and
selectivity, electrical and optical properties,
sensitivity to surface-enhanced Raman scattering
(SERS) and the Plasmon resonance and melting
point are also all highly shape-dependent
8. Importance of Core/Shell Nanoparticles
Emerged at the frontier between materials chemistry and many other fields, such as
electronics, biomedical, pharmaceutical, optics, and catalysis.
Core/shell nanoparticles are highly functional materials with modified properties.
Because of the shell material coating, the properties of the core particle such as
reactivity decrease or thermal stability can be modified, so that the overall particle
stability and dispersibility increases.
The purpose of the coating on the core particle are many fold, such as surface
modification, the ability to increase the functionality, stability, and dispersibility,
controlled release of the core, reduction in consumption of precious materials, and so
on.
Nano- and microsized hollow particles are used for different purposes such as micro
vessels, catalytic supports, adsorbents, lightweight structural materials and thermal
and electric insulators.
9. Techniques, Classifications & Mechanism Of Core/Shell Nanoparticle
Synthesis
In general, core/shell nanoparticles are synthesized using a two-step process, first synthesis of core and
second the synthesis of the shell.
The synthesis techniques of core/shell nanoparticles can be classified into two types depending on the
availability of core particles:
(i) the core particles are synthesized and separately incorporated into the system with proper surface
modification for coating the shell material;
(ii) the core particles are synthesized in situ, and this is followed by coating of the shell material.
The basic advantage of external core synthesis is the fact that core particles are available in pure form and
hence there is less possibility of impurities on the core surface.
Whereas, in situ synthesis, the main problem is that some impurity from the reaction media may be trapped
between the core and shell layer.
The most important step during synthesis of core/shell particles is to maintain uniform coating and to control
the shell thickness.
Some of the various synthetic methods for core/ shell particles used by different research groups are
precipitation, polymerization, micro emulsion, sol-gel condensation, layer by layer adsorption techniques etc.
10. 1) A nanoparticle carries the pharmaceutical agent inside its
core, while its shell is functionalized with a ‘binding’ agent
2) Through the ‘binding’ agent, the ‘targeted’ nanoparticle
recognizes the target cell. The functionalized nanoparticle
shell interacts with the cell membrane
3) The nanoparticle is ingested inside the cell, and interacts
with the biomolecules inside the cell
4) The nanoparticle breaks, and the pharmaceutical agent is
released
Nanotechnology – based drug delivery Systems
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12. Nano shells – Curing Tumors
Absorption of light by nanoshells
creates an intense heat that is lethal to
cells. These are used for early detection
of cancer and its treatment by
embedding drug containing tumor
targeted hydrogel polymer and injected
in the body .which when heated with
laser (infrared)and thus release drug at
tumor site .
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13. PLGA–lecithin–PEG core–shell nanoparticles for
controlled drug delivery
The development of biodegradable core–shell NP systems that combined the
beneficial properties of liposomal and polymeric NPs for controlled drug delivery.
These core–shell NPs are formed from three biomaterials:
(i)Poly(D,L-lactide-co-glycolide) (PLGA) was selected for the hydrophobic core
due to its biodegradable nature and have good mechanical properties for drug
delivery applications and ability to encapsulate high amounts of hydrophobic
drugs(chemotherapeutic drug Dtxl); PLGA is a diblock copolymer. It is capable of
carrying highly insoluble drugs with high loading capacity.
14. (ii) lecithin was chosen for a monolayer around the hydrophobic core;
(iii) Poly(ethylene)glycol(PEG) intersperses in the lecithin monolayer to
form a PEG shell which provides electrostatic and steric stabilizations, a
longer circulation half-life in vivo as well as functional-end groups for
the attachment of targeting ligands such as antibodies, peptides and
aptamers.
A modified Nano precipitation technique was used to prepare the NPs.
Preparation of the NPs showed that various formulation parameter such
as the lipid/polymer mass ratio and lipid/lipid–PEG molar ratio
controlled NP physical stability and size.
17. DLS was used to characterize NP hydrodynamic size, poly-dispersity and zeta potential in each
preparation. The average diameter of synthesized NPs ranged between 60 and 70 nm. The zeta potential ranged
between 40 mV and 60 mV, depending on the size and composition of the NPs. Regardless of Dtxl loading, the
particle sizes and zeta potentials remained in the same range. A schematic shows the core-shell structure of the
NPs, while TEM was used to examine the morphology of the NPs. The TEM images revealed that the NPs are
dispersed as individual NPs with a well-defined spherical shape and homogeneously distributed around 60-70
nm in diameter, and that the incorporation of Dtxl did not seem to cause morphological changes.
19. References
Encyclopedia of Nanoscience and Nanotechnology, 2004, v.1 & 7.
Handbook of Nanoscience, Engineering, and Technology, 2007.
Handbook of Nanotechnology,Springer,3rd edition.
Nanoparticle technology for drug delivery, volume 159 by Ram B Gupta.
journal homepage : www .elsevier .com /locate /biomaterials
PLGA-lecithin-PEG core-shell nanoparticles for controlled drug delivery by
Juliana M. Chan , Liangfang Zhang , Kai P. Yuet , Grace Liao , June-Wha
Rhee , Robert Langer , Omid C. Farokhzad.
Wikipedia.