Dr. Amira Taman, Ph.D. 1. Research in nanotechnology is rapidly progressing the development of new...
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Transcript of Dr. Amira Taman, Ph.D. 1. Research in nanotechnology is rapidly progressing the development of new...
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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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. 7
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. 10
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.11
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.14
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.15
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 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.19
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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