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Applications of Nanoparticles for Delivery of
Therapeutic Agents
Frank Jeyson Hernández
Topics of Nanobiotechnology 30 June, 2004
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Introduction
Significant effort has been devoted to develop
nanotechnology for drug delivery since it offers
a suitable means of delivering small molecular
weight drugs, as well as macromolecules such as
proteins, peptides or genes.
1 Advanced Drug Delivery Reviews 55 (2003)
329347.
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Introduction
Nanotechnology focuses on formulating therapeutic
agents in biocompatible nanocomposites such as
Nanoparticles Nanocapsules
Micellar systems
1 Advanced Drug Delivery Reviews 55 (2003)
329347.
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Introduction
These systems can be used to provide targeted
(cellular / tissue) delivery of drugs. Improve
oral bioavailability, to solubilize drugs for
intravascular delivery, and to improve the
stability of therapeutic agents against enzymatic
degradation.
1 Advanced Drug Delivery Reviews 55 (2003)
329347.
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Nanoparticles
2World Journal of Gastroenterology
200410(1)112-116
The nanometer size-ranges of these delivery
systems offer certain distinct advantages for
drug delivery. Due to their sub-cellular and
sub-micron size, nanoparticles can penetrate deep
into tissues through fine capillaries, cross the
fenestration present in the epithelial lining.
1 Advanced Drug Delivery Reviews 55 (2003)
329347.
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Intracellular Trafficking
Nanoparticles are internalized efficiently
through an endocytic process and that uptake is
concentration- and time-dependent. Efficiency
decreased at higher doses, suggesting that the
pathway is saturable.
1 Advanced Drug Delivery Reviews 55 (2003)
329347.
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Intracellular Trafficking
Following their uptake, nanoparticles are
transported through early endosomes. A fraction
of nanoparticles recycles back to the cell
exterior while another fraction is transported to
secondary endosomes/lysosomes from where
nanoparticles escape into the cytoplasm.
Nanoparticles that escape into the cytoplasm
could act as intracellular reservoirs for
sustained release of the encapsulated therapeutic
agent.
1 Advanced Drug Delivery Reviews 55 (2003)
329347.
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Therapeutic Application of Nanoparticles

• Sustained Gene Delivery

Rapid escape of nanoparticles from the
degradative endo-lysosomal compartment to the
cytoplasmic compartment and their sustained
intracellular retention suggest that
nanoparticles containing capsulated plasmid DNA
could serve as an efficient sustained release
gene delivery system.
1 Advanced Drug Delivery Reviews 55 (2003)
329347.
The generating a nonviral gene delivery vehicle
is reached.
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es/fig3.gif
3 Journal of Controlled Release 92 (2003)
199208
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Therapeutic Application of Nanoparticles

• Vaccine Adjuvant

The vaccine adjuvant is effective and safe,
which could also reduce the frequency of
immuniation. The nanospheres induce a systemic
immune response, which is almost comparable to
the immune response induced using alum as an
adjuvant.
6 J. Microencapsulation, 2000, VOL. 17, NO. 2,
215 225.
6 J. Microencapsulation, 2000, VOL. 17, NO. 2,
215 225.
The scanning electron micrograph of nanospheres
containing Staphylococcal Enterotoxin B.
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Tissue Targeting

• Targeted Drug Delivery Systems

Recent advances in biotechnology have enabled a
whole new generation of drug delivery systems in
which the drug is targeted to a specific site
using a recognition such as an antibody. This
approach has been fairly successful, resulting in
drug products such as sustained-release
formulations, transdermal patches, liposomes and
other colloidal delivery systems
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4 http//lysine.pharm.utah.edu/pceu_web/herron.h
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Tissue Targeting

• Liposomes

The liposomal drug carriers which are coated with
both antibody fragments (Fab) and poly(ethylene
glycol)(PEG). The Fab fragments serve as
recognition for to direct the liposomes to target
cells such as lymphomas, while the PEG molecules
enable the liposomes to "hide" from the reticular
endothelial system (RES)
Liposome filled with target drug
4 http//lysine.pharm.utah.edu/pceu_web/herron.h
tm
7 http//tubs.sa.utoronto.ca/pandp.htm
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Conclusions

• The nanoparticles are a potentially useful drug
  delivery system capable of delivering a multitude
  of therapeutic agents by targeted and/or
  sustained delivery.
• Also, as the pathophysiology of disease
  conditions and their cellular mechanisms are
  understood, drug delivery systems customized to
  achieve optimal therapeutic efficacy will be more
  effective.
• The versatility of nanoparticles for
  formulation, sustained release properties,
  sub-cellular size and biocompatibility with
  tissue and cells appear to be a promising system
  to achieve these important objectives.

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References
1 Jayanth Panyam , Vinod Labhasetwar,
Biodegradable nanoparticles for drug and gene
delivery to cells and tissue, Advanced Drug
Delivery Reviews 55 (2003) 329347. 2 Jing
Chen, Wu-Li Yang, Ge Li, Ji Qian, Jing-Lun Xue,
Transfection of mEpo gene to intestinal
epithelium in vivo mediated by oral delivery of
chitosan-DNA nanoparticles, World J Gastroenterol
200410(1)112-116. 3 Stephanie Rhaese, et.
al., H uman serum albuminpolyethylenimine
nanoparticles for gene delivery, Journal of
Controlled Release 92 (2003) 199208. 4
http//lysine.pharm.utah.edu/pceu_web/herron.htm
5 http//www.unmc.edu/pharmacy/labhasetwar/image
s/fig3.gif 6 Immune response with
biodegradable nanospheres and alum studies in
rabbits using staphylococcal enterotoxin
B-toxoid, M. P. Desai, J. Microencapsulation,
2000, VOL. 17, NO. 2, 215 225. 7
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Thank You Everyone!!!!