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PRESENTATION ON
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 of
manipulating matter at the nanoscale”
which is about 1 to 100 nanometers.
Nanotechnology
1.Medicine
2.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 Communication
4.Heavy Industries
i) Aerospace
ii) Refineries
iii) Vehicle manufactures
Fields using Nano Technology
 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.
iii) Gold nanoparticles tagged with short
segments of DNA can be used for detection of
genetic sequence in a sample.
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.
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 ability
Enhanced dosing requirements:
Lower dosed administered
Better side effect profile
More 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
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.
Mechanism of drug delivery: Dendrimer
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
Mechanism of drug delivery: Dendrimer
 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
Mechanism of drug delivery: Dendrimer
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 meta
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 Preparation
Lipid 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
Media and Methods that can affect Release
 Solvents
 pH
 Temperature
 Agitation
 Enzymes
 Cell culture
 Sink conditions
 Volume
 Sampling interval
Liposomes Help Improve
Therapeutic index
Rapid metabolism
Unfavorable pharmokinetics
Low solubility
Lack of stability
Irritation
Custom design
Lipid content
Size
Surface charge
Method 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
Micelle formation mechanism
 Stepwise growth model (Isodesmic
model)
Aggregation is a continuous process
broad aggregation, no cmc
 Closed aggregation model
Aggregation number n dominates
Micelle formation mechanism
H2O
Miclle as Drug Carrier
Miclle as Drug Carrier
- 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

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Novel drug delivery system nanotechnology

  • 2. Presented by NOVEL DRUG DELIVERY SYSTEM : NANOTECHNOLOGY Shamal Ghosh
  • 3. 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
  • 4. 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.
  • 5. 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)
  • 6. 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
  • 7. 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.
  • 8. 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.
  • 9. 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
  • 10. “Nanotechnology is the art and science of manipulating matter at the nanoscale” which is about 1 to 100 nanometers. Nanotechnology
  • 11. 1.Medicine 2.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 Communication 4.Heavy Industries i) Aerospace ii) Refineries iii) Vehicle manufactures Fields using Nano Technology
  • 12.  DRUG DELIVERY  THERAPY TECHNIQUES  ANTI – MICROBIAL TECHNIQUES  DIAGONISTIC  TISSUE ENGINEERING
  • 13. DRUG DELIVERY - Employing nanoparticles to deliver drugs. - Oral administration of drugs.
  • 14. THERAPY TECHNIQUES - Buckyballs - Nanoshells - Nanoparticles - Aluminosilicate Nanoparticles - Nanofibers
  • 15. ANTI-MICROBIAL TECHNIQUES - Nanoparticle Cream - Nanocapsules - Cell repairs using Nanorobots
  • 16. 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. iii) Gold nanoparticles tagged with short segments of DNA can be used for detection of genetic sequence in a sample.
  • 17.
  • 18. 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.
  • 19. 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
  • 20. Possible Opportunities for Nanotechnology in Drug Delivery Enhanced drug properties such as:  Solubility  Rate of dissolution  Oral bioavailability  Targeting ability Enhanced dosing requirements: Lower dosed administered Better side effect profile More convenient dosage forms
  • 21. FDA-Regulated Products Expected to be Impacted by Nanotechnology  Drugs (delivery systems)  Medical devices  Biotechnology products  Tissue engineering products  Vaccines  Cosmetics  Combination products
  • 22.
  • 23.  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
  • 24.  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
  • 27. drugs drug delivery –  Small molecules  Proteins  Tissue targeting Drug solublization RNA/DNA delivery Diagnostics & materials applications Applications in Pharmaceutical Industry
  • 28.  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
  • 29.  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
  • 30.  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
  • 31.  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. Mechanism of drug delivery: Dendrimer
  • 32. 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 Mechanism of drug delivery: Dendrimer
  • 33.  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 Mechanism of drug delivery: Dendrimer
  • 35.
  • 37. 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
  • 38. Liposome  Spherical vesicles with a phospholipid bilayer Hydrophilic Hydrophobic
  • 39. 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.
  • 40. 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
  • 41.  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
  • 42. Uses of Liposomes  Chelation therapy for treatment of heavy meta poisoning  Enzyme Replacement Diagnostic imaging of tumors  Study of membranes  Cosmetics  Drug Delivery
  • 43.  They can deliver agents directly into cells.  Routes:  Intravenous (iv)  Subcutenuous (sc)  Intramuscular (im)  Topical  Pulmonary Route of Liposomes in Drug Delivery
  • 44.  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
  • 45.  Doxil Daunorubicin 1995  Daunoxome Daunorubicin 1996  Ambisome Amphotericin B 1997  Depocyt Cytarabine 1999 APPROVED LIPOSOME PRODUCTS
  • 46. Liposome Preparation Lipid 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
  • 48. Critical factors in Liposome preparation  Particle size  Method of manufacture  Lipid types  Polymerization  Interfacial charge  Steric stabilization  Sterilization
  • 50. Media and Methods that can affect Release  Solvents  pH  Temperature  Agitation  Enzymes  Cell culture  Sink conditions  Volume  Sampling interval
  • 51. Liposomes Help Improve Therapeutic index Rapid metabolism Unfavorable pharmokinetics Low solubility Lack of stability Irritation Custom design Lipid content Size Surface charge Method of preparation
  • 52.
  • 53. 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).
  • 55.
  • 56.
  • 57.
  • 58.  Stepwise growth model (Isodesmic model)  Closed aggregation model Micelle formation mechanism
  • 59. Micelle formation mechanism  Stepwise growth model (Isodesmic model) Aggregation is a continuous process broad aggregation, no cmc
  • 60.  Closed aggregation model Aggregation number n dominates Micelle formation mechanism
  • 61. H2O
  • 62. Miclle as Drug Carrier
  • 63. Miclle as Drug Carrier
  • 64. - 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.

Notes de l'éditeur

  1. by definiton as you can see ”it’s the art of manipulating matter at the nanoscale level”