Transcript Document

Dr. Amira Taman, Ph.D.
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Research in nanotechnology is rapidly progressing
the development of new modalities for early
diagnosis and medical treatment beyond the
cellular level of individual organelles is the
goal of nanotechnology researchers.
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 Nanotechnology
is a general term refers to the techniques
and methods for studying, designing, and fabricating
devices at the level of atoms and molecules.
 The
word “nano” is derived from the Greek word
meaning ‘‘dwarf’’

In dimensional scaling nano refers to 10 -9
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
Nanotechnology is very important to biology since
many biological species have molecular structures at
the nano-scale levels such as:
 proteins
 carbohydrates
 lipids
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 Nanopharmaceuticals
have been targeted to every part
of the body and can even penetrate the tight epithelial
junctions of skin and endothelial interface of blood-
brain barrier (BBB) (through which 98% of drugs
cannot transverse), making high amount of drug
available to these tissues or organ.
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Nanopharmaceuticals to target antifilarials

Lymphatic filariasis (LF) is a major health problem in
many countries due to less efficient filariasis elimination
programs.

The deep-seated location of parasites within the complex
anatomy of host lymphatic system is a barrier resulting
in less bioavailability of antifilarial agents.
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Drastic advancement in existing LF treatment protocols is
expected to be achieved by reformulating antifilarial drugs
using nanopharmaceutical technology.
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Limitations associated with antifilarial agents for the treatment of LF.
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Advantages of using nano-medicine in
Lymphatic Filariasis
Improve solubility, plasma
half-life, overall
pharmacokinetics and
bioavailability of
antifilarial agents.
Provide lymphatic
targeted DDS to target
adult worm and
Wolbachia
endosymbionts.
Short treatment protocols
promoting patient
compliance to existing
treatment strategies.
Reduced dosage and dose
frequency
Provide a wide array of
multifunctional
nanoparticles to
overcome the billion fold
fear of drug resistance.
Reduced toxicity of
antifilarials
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Drug Delivery Systems (DDSs)

DDSs are polymeric or lipid carriers

They can effectively transport therapeutics to their target
sites.
Advantages
1.
Achieve maximum pharmacological effects
2.
Minimum adverse reaction
3.
Preventing the degradation/denaturation/ inactivation of therapeutic
agents.
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DDS target antifilarial agent to adult worms, Wolbachia or
microfilaria (mf), should have the following characteristics:
 Optimal
size range of nanoparticles.
 Efficient
uptake into the lymphatic system.
 High
uptake in the lymph nodes.
 Ability
to slow release of antifilarial agents to the
parasites.
 Prolong
retention of drug in blood circulation to eliminate
(mf).
 Low
toxicity to normal, healthy tissues.
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Modifying the surface
characteristics.
Attaching specific
ligands to the DDS.
Attaching specific
molecules to the DDS.
Techniques
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solid lipid
Carriers
polymeric
nanoparticles
Liposomes
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Liposomes to target mf and adult parasites

Liposomes are the first nanocarriers employed for the
improvement of antifilarial drugs.

Liposomes have been well studied for their accumulation in
lymph nodes or enhancing targeting to lymphatic system via
subcutaneous route.

Antibody-sensitized liposomes or immunoliposomes (as
“guided missiles”) also effectively evade mononuclear
phagocytic clearance and are considered vital for boosting
the bioavailability of microfilaricides.
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Liposomes to target endosymbiotic bacteria Wolbachia

Tetracycline, doxycycline, and rifampicin are some of the
antirickettsial antibiotics found effective against Wolbachia and
can interrupt the symbiotic association between worm and
bacteria, causing death of filarial worm.

Treatment is needed for a long duration to achieve the absolute
elimination of Wolbachia, resulting in acute toxicity.

Liposomized tetracycline was found more competent than the free
form of drug, reducing the treatment plan to 12 alternate days with
better efficacy in contrast to 90/120 days oral administration of the
free drug.
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SLNs to target antifilarials
 Solid
lipid nanoparticles (SLNs) are attractive
pharmaceutical carriers formed of solid lipids that
remain solid at room temperature.
 These
nanoparticles put forward certain additional
advantages over other carriers in terms of toxicity,
biocompatibility, and controlled drug-release kinetics.
 SLNs
to target intracellular bacteria Wolbachi.
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Polymeric nanoparticles

Polymeric nanoparticles are colloidal particles, ranging
in size from 1 to 1000 nm.

A variety of biocompatible and biodegradable
polymeric matrices are available for their preparation.

In the recent years, polymer-based DDSs had widely
been used for the treatment of parasitic diseases and
site-specific targeting of diagnostic agents to the
lymphatic system.
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Optimal particle size range for antifilarial drug delivery

From the previous studies, the researchers suggest
20-- 70 nm diameter as the most favorable size range
of nanocarriers for lymphatic targeting of antifilarials.
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Surface engineering for enhanced localization of
antifilarials in the lymphatic system

Surface characteristics of nanoparticles have
fundamental importance to interact with the environment

Owing to the peculiar anatomy of lymphatic system and
interstitial resistance exerted by osmotic pressure that
prevent particles uptake, surface modifications of
polymeric nanoparticles are essential to enhance
localization of antifilarials close to lymph-resident
filaroids.
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
Some ligands may prove useful for filarial treatment are
Hyaluron, L-selectin, lectin, folate, dextrin.

Mannose attached to liposome surface increases lymph node
uptake by threefold compared with control liposomes and is used
to improve the delivery of antifilarials to lymph nodes.

Also, Wolbachia, expose mannose receptors on their surface
and attract lectin-coated nanoparticles to target these bacteria.
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Avoidance of reticuloendothelial system for systemic elimination of
nanoparticles

Uptake via RES can be avoided by coating of nanoparticles
with hydrophilic polymers such as PEG and poloxamine.

The proposed mechanism for this is that these hydrophilic
polymers result in adsorption of proteins on the surface of
the nanoparticles which decrease opsonization in vivo.
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Thank you
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