Novel drug delivery system nanotechnology

PRESENTATION ON

NOVEL DRUG DELIVERY SYSTEM : NANOTECHNOLOGY

Presented by

NOVEL DRUG DELIVERY SYSTEM : NANOTECHNOLOGY

Shamal Ghosh

Contents

Drug delivery Targeted drug delivery Nanotechnology F i e l d s u s i n g n a n o t e c h n o l o g y Dendrimers Applications in drug delivery (dendrimers) Mechanism of drug delivery (dendrimers) Liposome Liposomes in drug delivery Liposome preparation Micelle Micellar shape Micelle formation mechanism Miclle as drug carrier

Drug Delivery

Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect.

Drug delivery technologies that modify Drug release profiles Absorption Distribution Elimination

for the benefit of improving product efficacy and safety and patient convenience and compliance.

Drug Delivery

Most common methods of delivery include the

Non-invasive peroral (through the mouth) Topical (skin) Transmucosal (nasal, buccal/sublingual, vaginal,

ocular and rectal) Inhalation routes. Parental (IV, IM, IA, ISp etc)

Generation of Drug Delivery System

1st Generation 2nd Generation

3rd Generation

4th Generation

5th Generation

Tablet

Capsule

Ointment

Suspension

Emulsion

Suppositories

Repeat action tablet

Prolonged action tablet

Enteric Coated tablet

Timed Release tablet

Osmotically Control System

Swelling Controlled

Magnetic Controlled System

Diffusion Controlled System

Targeted DDS

Modulated DDS

Self Regulated DDS

Gene Therapy

TARGETED DRUG DELIVERY

Targeted drug delivery, sometimes called smart drug delivery

• A method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others.

• The goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue.

Advantage of targeted drug delivery system over traditional drug delivery system

• Increased efficacy of the drug.• Site specific delivery.• Decreased toxicity/side effects.• Increased convenience.• Better patient compliance.• Viable treatments for previously incurable

diseases.

Novel drug delivery system

It is advance drug delivery system which improve

• Drug potency• Control drug release to give a sustained

therapeutic effect• Provide greater safety• Finally it is to target a drug specifically to a

desired tissue

“Nanotechnology is the art and science ofmanipulating matter at the nanoscale”

which is about 1 to 100 nanometers.

Nanotechnology

1.Medicine2.Energy i) Reduction of energy consumption ii) Increasing the efficiency of energy production iii) The use of more user friendly energy systems

3.Information and Communication4.Heavy Industries i) Aerospace ii) Refineries iii) Vehicle manufactures

Fields using Nano Technology

NANOTECHNOLOGY IN MEDICINE

DRUG DELIVERY THERAPY TECHNIQUES ANTI – MICROBIAL TECHNIQUES DIAGONISTIC TISSUE ENGINEERING


DRUG DELIVERY - Employing nanoparticles to deliver

drugs. - Oral administration of drugs.


THERAPY TECHNIQUES - Buckyballs - Nanoshells - Nanoparticles - Aluminosilicate Nanoparticles - Nanofibers

ANTI-MICROBIAL TECHNIQUES - Nanoparticle Cream - Nanocapsules

- Cell repairs using Nanorobots


i) Nanotechnology-on-a-chip is one more dimension of lab-on-a-chip technology.

ii) Magnetic nanoparticles, bound to a suitable antibody, are used to label specific molecules, structures or microorganisms.

i i i ) Go ld nanoparti c les tag ged with short segments of DNA can be used for detecti on of geneti c sequence in a sample .

DIAGNOSTICS

i) Nanotechnology can help to reproduce or to repair damaged tissue.

ii) “Tissue engineering” makes use of artificially stimulated cell proliferation by using suitable nanomaterial-based scaffolds and growth factors.

iii) Tissue engineering might replace today’s conventional treatments like organ transplants or artificial implants. Advanced forms of tissue engineering may lead to life extension.

TISSUE ENGINEERING

Applications of Nanoparticles to Drug Discovery and Biology

Fluorescent biological markers Detection of proteins Probing of DNA structures MRI contrast enhancement Separation and purification of biological

molecules and cells Tumor destruction via heating Tissue engineering Drug and gene delivery

Possible Opportunities for Nanotechnology in Drug Delivery

Enhanced drug properties such as: Solubility Rate of dissolution Oral bioavailability Targeting abilityEnhanced dosing requirements:

Lower dosed administeredBetter side effect profileMore convenient dosage forms

FDA-Regulated Products Expected to be Impacted by Nanotechnology

Drugs (delivery systems) Medical devices Biotechnology products Tissue engineering products Vaccines Cosmetics Combination products

Tree-like polymers, branching out from a central core and subdividing into hierarchical branching units

- Not more that 15 nm in size, Mol. Wt very high

- Very dense surface surrounding a relatively hollow core (vs. the linear structure in traditional polymers)

Dendrimers

In 2008 there were over 10 000

scientific reports and 1000 patents

dealing with dendritic structures.

Courtesy of: http://www.uea.ac.uk/cap/wmcc/anc.htm

Dendrimers

Dendritic Family

Structural Components of Dendrmers

http://commons.wikimedia.org/wiki/File:Micelle_scheme-en.svg

drugs

drug delivery – Small molecules Proteins Tissue targeting

Drug solublization

RNA/DNA delivery

Diagnostics & materials applications

Applications in Pharmaceutical Industry

Improved efficacy of drugs Extension of drug half-life Reduced toxicity Active or passive targeting Product lifecycle

management Improved solubility of drugs Drug “rescue”

Applications in Drug Delivery

Utilizing a dendrimer construct the aqueous solubility of the drug Paclitaxel was increased >9,000X.

Paclitaxel aqueous solubility 0.8 mg/mL

Improved Drug Solubility

Dendrimers are particularly attractive as they offer a high drug-loading capacity.

2 methods of dendrimer drug delivery are Encapsulation of drugs Dendrimer –drug conjugates

Mechanism of drug delivery: Dendrimer

Interactions between the dendrimer and drug to trap the drug inside the dendrimer.

Such a system can be used to encapsulate drugs and provide controlled delivery.

,eg: DNA was complexed with PAMAM dendrimers for gene delivery applications, and hydrophobic drugs and dye molecules were incorporated into various dendrimer cores.


Dendrimer–Drug Conjugates In dendrimer–drug conjugates, the drug is attached through a covalent bond either directly or via a linker/spacer to the surface groups of a dendrimer.

Dendrimers have been conjugated to various biologically active molecules such as drugs, antibodies, sugar moieties and lipids


The drug loading can be tuned by varying the generation number of the dendrimer

Release of the drug can be controlled by incorporating degradable linkages between the drug and dendrimer

Conjugates of PAMAM dendrimers with cisplatin, a potent anticancer drug with non-specific toxicity and poor water solubility.

The conjugates show increased solubility, decreased systemic toxicity and selective accumulation in solid tumors


Drugs Delivered Through Dendrimers

Phospholipids

Polar Head Groups

Three carbon glycerol

An artificial microscopic vesicle consisting of an aqueous core enclosed in one or more phospholipid layers.

Used to convey vaccines, drugs, enzymes, or other substances to target cells or organs.

Liposome

Liposome

Spherical vesicles with a phospholipid bilayer

Hydrophilic

Hydrophobic

Liposomes can be subcategorized

Small unilamellar vesicles (SUV), 25 to 100 nm in size that consist of a single lipid bilayer

Large unilamellar vesicles (LUV), 100 to 400 nm in size that consist of a single lipid bilayer

Multilamellar vesicles (MLV), 200 nm to several microns, that consist of two or more concentric bilayers

Vesicles above 1 µm are known as giant vesicles.

1. Conventional Liposomes

Prepared form natural neutral and anionic lipids and have nonspecific interactions with their environment

Relatively unstable Have low carrying capacities Tend to be “leaky” to entrapped drug substances .

Types of Liposomes

Non-conventional Liposomes

Small sized, surface modified to overcome some of the short comings of conventional liposomes

Modified to reduce negative charge, decrease fluidity and cause steric hinderance to phagocytosis

Properties altered (e.g. by incorporation of cholesterol)

Polymerized liposomes more stable and less “leaky”

Types of Liposomes

Uses of Liposomes

Chelation therapy for treatment of heavy metal poisoning

Enzyme Replacement Diagnostic imaging of tumors

Study of membranes

Cosmetics

Drug Delivery

They can deliver agents directly into cells.

Routes: Intravenous (iv) Subcutenuous (sc) Intramuscular (im) Topical Pulmonary

Route of Liposomes in Drug Delivery

Improved therapeutic response Achieve appropriate tissue or blood levels

Reduced adverse reactions Less drug administered Targeted drug release

Lower dosing frequency Improved patient compliance Simpler dosing regimens Lower cost per dose

Advantages of Liposomes in Drug Delivery

Doxil Daunorubicin 1995 Daunoxome Daunorubicin 1996 Ambisome Amphotericin B 1997 Depocyt Cytarabine 1999

APPROVED LIPOSOME PRODUCTS

Liposome PreparationLipid in organic solvent solutionEvaporation

Extrusion (or sonication)

Liposomes and unencapsulated SRB

Lipid film

Freeze/thaw cycles

Gel filtration

Purified liposomes

Hydrate with sulforhodamine B (SRB) solution

Liposome Preparation

Critical factors in Liposome preparation

Particle size Method of manufacture Lipid types Polymerization Interfacial charge Steric stabilization Sterilization

Modes of Liposome/Cell Interaction

Adsorption Endocytosis

Fusion Lipid transfer

Media and Methods that can affect Release

Solvents pH Temperature Agitation Enzymes Cell culture Sink conditions Volume Sampling interval

Liposomes Help Improve

Therapeutic indexRapid metabolismUnfavorable pharmokineticsLow solubilityLack of stabilityIrritation

Custom designLipid contentSize

Surface chargeMethod of preparation

Micelle

Micelles are like tiny balls of molecules. They are made out of amphipathic molecules. An amphipathic molecule is a molecule that is

Both hydrophilic (polar) and hydrophobic (non-polar).

A micelle is a ball that forms when amphipathic molecules are put in a liquid. The liquid can be polar (like water) or non-polar (like butane or octane).

MICELLAR SHAPE

Stepwise growth model (Isodesmic model)

Closed aggregation model

Micelle formation mechanism


Stepwise growth model (Isodesmic model)

Aggregation is a continuous process

broad aggregation, no cmc

Closed aggregation model

Aggregation number n dominates


OH

H

O

HH

OH

H

Surfactant Micelle

Hydrophilic

Hydrophobic

OH

H

O

HHO

HH

O

H

H

OH

H

OH

H

H2O

Miclle as Drug Carrier

SUMMARY AND CONCLUSION

- From being a theory to something we can now see, words turned into reality.

- Nanotechnology has evolved over the period of time for many decades, and is now showing its potential to the whole world.

- The development of nanomachines such as: I-switch, nanoimpellers, nanobots etc.

- Nanotechnology will increase your standard of living.- Up to today nanotechnology is what's in, what's new, and

what's the latest technology being developed all over the world.

FOR THE ATTENTION

Novel drug delivery system nanotechnology

Education

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