Post on 10-Feb-2018
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Outline1. Introduction: Nanocarriers and Trandermal
Drug Delivery Systems (TDDS)
2.Structure of skin and absorption mechanism
3. Nanocarriers for transdermal drug delivery
4.Applications of nanocarriers in TDDS
5.Advantages and limitations
6. Conclusion
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Nanotechnology An integral part of the twenty first century.
NANOCARRIERS: (NC) Colloidal systems having structures below a particle or
droplet size of 500 nm.
Nano materials(Nanostructures)- Capable to carry
drugs through the body, made of a lot of differentmaterials and very different in structure and chemical
nature.
So small to be detected by immune system and they
can deliver the drug in the target organ
NCs applied to the skin are in the center of attention
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Nanocarriers (NCs)
Valuable alternative for delivering lipophilic
and hydrophilic drugs
The desired effects:
The local effect within the skin (Dermal
drug delivery)
The systemic effect accompanied by
the permeation through the skin
(Transdermal drug delivery)
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Methods of NanotechnologyBased on Drug Delivery
NANOCARRIERS
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Transdermal Drug Delivery Systems (TDDS)
Self contained, discrete dosage forms which, when
applied to the intact skin, deliver the drug, through theskin at controlled rate to the systemic circulation.
An integral part of novel drug delivery systems.
Application of a pharmacologically active compound
on to the skin to achieve therapeutic blood levels in
order to treat diseases remote from the site of
application.
Current transdermal therapeutics formulations
Traditional formulations (Gels)
Advanced delivery systems (Patches)
Novel physical technologies (Microporation,iontophoresis, and sonophoresis).
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ADVANTAGES
1. Avoidance of significant
presystemic metabolism, thus
the need for a lower daily dose
2. Reduced dosage related side-
effects.
3. Drug input can be terminated
simply by removal of patch.
4. Longer Duration of action,
Frequency of dosing is
decreased.5. Patient compliance and
acceptability of the drug therapy.
DISADVANTAGES
1. Limited to potent drug molecule.
2. Pharmacokinetic,
pharmacodynamic characteristics
(sustained, slow input ).
3. Physicochemical properties of
drug should allow to be absorbed
percutaneously.
4. Drugs must not be locally
irritating or sensitizing.
5. Drugs with short biological half-
lives cannot be delivered
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STRUCTURE OF THE SKIN
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SCHEMATIC REPRESENTATION OF PENETRATION ROUTES (PATHWAYS)
OF DRUGS THROUGH THE SKIN
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CLASSIFICATION OF NANOCARRIERS
USED FOR TRANSDERMAL DRUG DELIVERY
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INFLUENCE OF MAIN PHYSICOCHEMICAL PROPERTIES OF
NANOCARRIER SYSTEMS ON CELL UPTAKE
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Most popular nano drug carrier.
Spherical vesicles that comprise one or several lipidbilayer(s) without surface tension enclosing an aqueous
core
Protect encapsulated drugs from degradation
Conventional liposomes:
Stiff bilayers (To prevent undesirable drug leakage)
An average diameter above 75 nm
Exterior lipid bilayer is very chemically reactive, -a
means to conveniently couple tags (antibodies,
antigens, cell receptors, nucleic acid probes, etc.)on a
covalent basis.
LIPOSOMES
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LIPOSOMEScontd
Lipoplexes : That encapsulate DNA or RNA in their
aqueous space for delivery to cells.
Unilamellar liposomes: Spherical concentric
unilamellar (one bilayer) structures Small and
Large (SUV and LUV)
Multilamellar liposomes: Spherically concentric
multilamellar (many bilayers) structures
TRANSFERSOMES
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TRANSFERSOMES
Highly Deformable(Elastic or Ultraflexible) liposomes
Presence of surfactants as an edge activator that destabilizes
the vesicle, - more flexibility and deformability.
Surfactants:
Tween 20, tween 80, sodium cholate, sodium deoxycholate,
dipotassium glycyrrhizinate, and oleic acid
Range in size from 200 to 300 nm.
Squeeze through skin pores (2030 nm) and reach deeper
layers in the skin.
Penetrate the skin intact . Do not penetrate through the transappendageal
pathways
Degree of penetration depends on amount of applied per
surface area of the skin
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Mechanism of skin penetration of deformable
vesicles
Transfersomal insulin (Transfersulin)
Insulin incorporated into lipid-based transfersomes
(Phosphatidylcholine-based drug carriers) is applied to intact
skin
Reduce plasma glucose concentration by ~20%; within 34 h.
Effect lasts for 10 h, is equivalent to 75100 % of
hypoglycaemic
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Ethanol (20% to 45%) containing phospholipid vesicles, by
mixing them with a constant stream of aqueous solution in
a sealed container Imparts high flexibility to the vesicles, enhanced solubility
Enhance drug delivery through skin under both
nonoccluding and occluding conditions
Release of ethanol from the ethosomes- fluidizes theskin lipids to increases skin permeation
ETHOSOMES
LIPID NANOPARTICLES (LN )
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LIPID NANOPARTICLES (LNs)
Superior physical stability
Made of solid lipids or a combination of solid and liquid
lipids
Solid Lipid Nanoparticles(SLNs)
Nanostructured lipid carriers (NLCs)
Advantages:
Solid lipid shell prevents drug leakage and degradation .
Increased surface area from the lipids increases their
adhesiveness to the skin.
Increased skin hydration, which, in turn, reduces the
corneocyte packing and increases skin penetration
SLN NLC
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SLN
Delivery systems for
hydrophobic drugs
Versatility - various routes
of administrations : oral,
parenteral, dermal, ocular
NLC
Flexibility in modulating
drug encapsulation and
drug release
Higher drug
encapsulation
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NIOSOMES
The hydrophobic part of the surfactant face toward the core,
whereas the hydrophilic groups interface with the surrounding
aqueous medium.
Niosomes Contd
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Niosomes. Contd
Mainly localized in the Stratum Corneum (SC), can
also penetrate deeper layers of the skin.
More stable and less expensive than liposomes.
Potential for controlled and targetted drug delivery.
Thermoresponsive (Polyhedral niosomes) and
release the encapsulated drug when heated above
35C.
Useful for sunscreen formulations
Delivery of antimonials for Leishmaniasis
MICELLE / MICELLAR NANO PARTICLES
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MICELLE / MICELLAR NANO PARTICLES
(MNP)
An aggregate of amphipathic molecules in water, with the
nonpolar portions in the interior and the polar portions at the
exterior surface, exposed to water.
Can accommodate both water-soluble and poorly water-
soluble Active Pharmaceutical Ingradients( APIs) .
S h ti t ti
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Micro/nanostructures within an
MNP formulation showing the
different API components
Deposition and disposition of MNP
structures within skin layers showing
stratification of API.
Schematic representation
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MNPs contd
Attractive alternatives for systemic drug
delivery via topical application.
Deliver drugs topically (skin being the site
of action) or transdermally (systemic
availability).
Functionally create a drug depot in the SC
and epidermis.
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NANOEMULSION
Athermodynamically stable and visually clear disperse
system of oil and water with a high proportion of
surfactants.
Typically contain 20500 nm large droplets
Use hydrophobic and hydrophilic drugs.
Non-toxic and non-irritant systems .
Used for skin or mucous membranes, parenteral and
non parenteral administration( in cosmetic field).
Higher skin penetration ,penetrate through the hairfollicles
Stability. ???...Lesser use nowadays.
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NANOPARTICLES
Nanoparticles are smaller than 1,000 nm.
Possible to insert many types of materials such as drugs, proteins,
peptides, DNA, etc. into the nanoparticles.
Constructed from materials designed to resist pH, temperature,
enzymatic attack, or other problems.
Nanospheres (Solid-core structures )
Nanocapsules (Hollow-core)
Polymers used :Polymethacrylate
polybutyl cyanoacrylate,
polycaprolactone,
chitosan
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DENDRIMERS
Highly branched polymers with a controlled three-
dimensional structure. around a central core.
Accommodate more than 100 terminal groups
The particle size - 1 to 10 nm.
Multivalent interactions with the biological membranes .
Unique architecture
Drugs can be encapsulated
Inside the core (Nanocontainers).
Complexed, or conjugated to the surface
functionalgroups (Nanoshells).
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Dendrimers: Schematic representation
ADVANTAGES OF DENDRIMERS
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ADVANTAGES OF DENDRIMERS
Suitable for targeting solid tumours due to increased
permeability, limited drainage in tumour vasculature which will
lead to accumulation of macromolecules in tumour (Enhanced
permeation rate).
Increase in therapeutic efficacy, decrease in side effects.
Drugs easily made to remain within layers of skin and not
penetrate in systemic circulation.
Medication to the affected part inside a patient's body directly.
Controlled and sustained release of drugs.
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Large insoluble drug crystals are milled to form nano-sized
particles with less than 2000 nm.
The decrease in drug particle size to nanoscopic crystals
results in an increased surface area to volume ratio.
Explored to increase oral bioavailability of sparingly watersoluble drugs.
NANOCRYSTALS
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Nano-sized tetrahedral network
Potentially protect drugs trapped inside ND agglomerates due
to high surface energy relative to their small size.
Potential in drug nanoformulations for melanoma therapy
NANODIAMONDS
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CUBOSOMES
Honeycombed (cavernous) structures separating two internal
aqueous channels and a large interfacial area.
Nanoformulations for melanoma therapy
Encapsulate hydrophobic, hydrophilic and amphiphilic
substances, targeting and controlled release of bioactive agents
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Nanostructures composed of amphiphilic block copolymers
Size range from 50 nm to 5 m
Encapsulate drugs inside vesicle membrane. Potentially offers a protective barrier to proteins peptides, DNA
and RNA fragments against deleterious factors that may bepresent in the biological environment.
Potential in melanoma therapy
POLYMERSOMES
APPLICATIONS
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APPLICATIONS
Liposomes :
Moisturizing and smoothening effect
To deliver skin protectants, antioxidants, and skin-whiteningagents.
For DNA delivery in gene therapy.
For many antifungal and anticancer agents.
Eg: Melatonin, indinavir, methotrexate, amphotericin B,ketoprofen,
estradiol, clindamycin and lignocaine.
Vesicular systems :
To deliver hydrophilic ,hydrophobic cosmetic agents
Improve skin retention, sustain release of the agents.
Lipid nanoparticles:
To deliver sunscreen agents.
SLNs improve the skin protection from UV radiation.
Deformable liposomes, ethosomes, and niosomes :
Topical and transdermal applications in : dermatitis,acne soriasis skin carcinomas. melanoma where
Transfersomes
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Transfersomes
Improve in vitro skin delivery of drugs
Efficiency comparable to subcutaneous administration.
Eg: Diclofenac, insulin, tetanus toxoid, corticosteroids,
superoxide dismutase, DNA, triamcinolone and ketoprofenEthosomes
In atopic dermatitis, Parkinsonian syndrome
Eg: Tacrolimus, clotrimazole, ketoprofen and testosterone
Niosomes
In hair loss.
They increase the residence time of drugs in the stratumcorneum and epidermis, while reducing systemic absorption ofdrug.
Eg: Minoxidil and ellagic acid.
Dendrimers
Gene therapy, Delivery of contrast agents, controlled drugdelivery,
Used in antiviral and anticancer pharmaceutical therapies,including vaccines..
Eg: Tamsulosin, indomethacin, ketoprofen, diflunisal and
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ADVANTAGES AND DISADVANTAGES OF NANOCARRIER SYSTEMS
Nanoparticles
Made of a lot of biodegradable materials.
Both hydrophilic and hydrophobic drugs
Not enough toxicological assessment has been done.
Difficult to develop an analytical method for drug delivery.
Niosomes, Transfersomes, Ethosomes
Biodegradable and low toxicity., Easy to prepare. Softness,malleability.
Predisposition to oxidative degradation.
Purity of natural phospholipids.?
Formulations are expensiveNanoemulsions
Can be formulated as foams, liquids, creams, and sprays.
Nontoxic and nonirritant. Easily applied to skin and mucous
membranes
Surface charge has a marked effect on stability.
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Veterinary Applications
Nanoemulsions :
Controlled release of injectable poorly water-soluble
drugs
In the delivery of controlled amounts of drugs inbreeding animals.
Other potential applications of nanotechnology in
veterinary medicine and animal health.
Treatment of Feline Hyperthyroidism.
Utilization, modification of animal waste as
expelled from the animal.
Pathogen detection, sensory and surgical aids.
CONCLUSION
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CONCLUSION
Nanocarriers
Increasing treatment efficiency
Reducing side effects, An increased activities as well as
prolonged activities
Presently, Polymeric nanoparticles, liposomes, dendrimers,
cubosomes,polymersomes and niosomes
Potential in treatment of skin cancers
The risk ratio for many drugs included in nanocarriers; and nano
toxicity ??.