Nanocarriers for Transdermal Drug Delivery

7/22/2019 Nanocarriers for Transdermal Drug Delivery

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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 ??.

Nanocarriers for Transdermal Drug Delivery

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