This document provides an overview of targeted drug delivery systems. It discusses the ideal characteristics of targeted systems including being nontoxic and allowing controlled drug release at the target site. The main advantages are reducing toxicity by delivering drugs only to the intended site and using smaller doses. Carriers like polymers, liposomes and dendrimers can be used to selectively target drugs. Strategies include passive, active and ligand-mediated targeting. Various nanotechnology approaches are also described like nanotubes, nanoshells and nanobots that aim to more precisely deliver drugs.
‘Targeted drug delivery system is a special form of drug delivery system where the medicament is selectively targeted or delivered only to its site of action or absorption and not to the non-target organs or tissues or cells.’
‘Targeted drug delivery system is a special form of drug delivery system where the medicament is selectively targeted or delivered only to its site of action or absorption and not to the non-target organs or tissues or cells.’
This will provide you the introduction about the tumor, its Anatomy & Physiology,How they are monitored?, Classification and grades of tumor, Tumor Targeting Techniques, strategies and Principles. Also provide you some examples of Marketed products.
Brief description of targeted drug delivery system, along with its concept and strategies for drug targeting. Advantages and disadvantages of drug targeting
Need for drug targeting.
This will provide you the introduction about the tumor, its Anatomy & Physiology,How they are monitored?, Classification and grades of tumor, Tumor Targeting Techniques, strategies and Principles. Also provide you some examples of Marketed products.
Brief description of targeted drug delivery system, along with its concept and strategies for drug targeting. Advantages and disadvantages of drug targeting
Need for drug targeting.
Targeted Drug Delivery Systems:
Targeted drug delivery systems (TDDS) are a revolutionary approach in medicine that aims to deliver medications directly to diseased cells or tissues, minimizing exposure to healthy parts of the body. This strategy offers numerous advantages over traditional drug delivery methods, including:
Reduced side effects: By minimizing drug exposure to healthy tissues, TDDS can significantly reduce the risk of adverse reactions and improve patient tolerability.
Increased efficacy: Delivering drugs directly to their target site allows for higher drug concentrations at the diseased area, potentially leading to improved treatment outcomes.
Enhanced specificity: TDDS can be designed to target specific biomarkers associated with diseases, offering greater precision and personalized treatment options.
Here's a closer look at the key components and mechanisms of TDDS:
Components:
Drug: The therapeutic agent encapsulated within the delivery system.
Carrier: A biocompatible material that encapsulates and protects the drug, facilitating its transport and release. Examples include liposomes, nanoparticles, and polymers.
Targeting moiety: A molecule attached to the carrier that specifically binds to receptors on the target cells or tissues, guiding the delivery system to its designated location. Antibodies, peptides, and aptamers are commonly used targeting moieties.
Mechanisms:
Passive targeting: Utilizes the natural properties of the carrier or targeting moiety to accumulate in the target area due to factors like size, charge, or permeability.
Active targeting: Employs specific interactions between the targeting moiety and receptors on the target cells, ensuring precise delivery.
Types of TDDS:
Liposomal drug delivery: Liposomes are microscopic bubbles made of phospholipids that can encapsulate drugs and deliver them to specific cells.
Polymeric nanoparticles: Nanoparticles made of biodegradable polymers can be designed to release drugs in a controlled manner at the target site.
Antibody-drug conjugates (ADCs): Antibodies are linked to cytotoxic drugs, allowing them to specifically target and kill cancer cells.
Aptamer-based drug delivery: Aptamers are short, single-stranded DNA or RNA molecules that can bind to specific targets with high affinity, guiding drug delivery.
Benefits of TDDS:
Improved treatment outcomes
Reduced side effects
Enhanced patient compliance
Personalized medicine options
Challenges of TDDS:
Complex design and development
Regulatory hurdles
Higher costs compared to traditional drugs
Future of TDDS:
Research in TDDS is rapidly advancing, with new technologies and targeting strategies emerging constantly. The future holds promise for even more precise and effective drug delivery systems, revolutionizing the treatment of various diseases.
Rate Controlled Drug Delivery Systems, Activation Modulated Drug Delivery Systems, Mechanically activated, pH activated, Enzyme activated, Osmotic activated Drug Delivery Systems, Feedback regulated Drug Delivery Systems systems are discussed here.
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2. CONTENTS :
• Introduction
• Ideal characteristics
• Advantages
• Disadvantages
• Carrier or markers
• Strategies of drug targeting
• Types of targeted drug delivery system
3. INTRODUCTION :
‘Targeted drug delivery system is a special form of drug
delivery system where the medicament is selectively
targeted or delivered only to its site of action or
absorption and not to the non-target organs or tissues or
cells.’
•It is 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.
•Targeted drug delivery seeks to concentrate the medication
in the tissues of interest while reducing the relative
concentration of the medication in the remaining tissues.
• This improves efficacy and reduce side effects.
4. THE DRUG MAY BE DELIVERED :
•To the capillary bed of the active sites.
•To the specific type of cell (or) even an intracellular
region. Ex: Tumour cells but not to normal cells.
•To a specific organ (or) tissues by complexion with the
carrier that recognizes the target.
OBJECTIVE :
•To achieve a desired pharmacological response at a
selected sites without undesirable interaction at othersites,
there by the drug have a specific action with minimum
side effects & better therapeutic index.
•Ex- In cancer chemotherapy and enzyme replacement
therapy.
5. REASON FOR DRUG TARGETING :
•In the treatment or prevention or diseases.
•Pharmaceutical drug instability in conventional dosage
form solubility ,biopharmaceutical low absorption, high-
membrane bounding, biological instability,
pharmacokinetic / pharmacodynamic short half life, large
volume of distribution, low specificity, clinical, low
therapeutic index.
6. IDEAL CHARACTERISTICS :
•It should be nontoxic, biocompatible, biodegradable,
and physicochemical stable invivo and invitro.
•Restrict drug distribution to target cells or tissues or
organs and should have uniform capillary distribution.
• Controllable and predicate rate of drug release.
• Drug release does not effect the drug action.
• Therapeutic amount of drug release.
• Minimal drug leakage during transit.
•Carriers used must be bio-degradable or readily
eliminated from the body without any problem and no
carrier induced modulation of diseased state.
•The preparation of the delivery system should be easy or
reasonably simple, reproductive and cost effective.
7. ADVANTAGES :
•Drug administration protocols may be simplified.
•Toxicity is reduced by delivering a drug to its target site,
there by reducing harmful systemic effects.
•Drug can be administered in a smaller dose to produce the
desire effect.
• Avoidance of hepatic first pass metabolism.
•Enhancement of the absorption of target molecules such as
peptides and particulates.
•Dose is less compared to conventional drug delivery
system.
•No peak and valley plasma concentration.
•Selective targeting to infections cells that compareto
normal cells.
8. DISADVANTAGES :
•Rapid clearance of targeted systems.
•Immune reactions against intravenous administered carrier
systems.
•Insufficient localization of targeted systems into tumour
cells.
•Diffusion and redistribution of released drugs.
•Requires highly sophisticated technology for the
formulation.
•Requires skill for manufacturing storage, administration.
•Drug deposition at the target site may produce toxicity
symptoms.
•Difficult to maintain stability of dosage form.
E.g.: Resealed erythrocytes have to be stored at 40 C.
•Drug loading is usually law. E.g. As in micelles.Therefore
it is difficult to predict /fix the dosage regimen.
9. CARRIER OR MARKERS :
•Targeted drug delivery can be achieved by using
carrier system.
•Carrier is one of the special molecule or system
essentially required for effective transportation of loaded
drug up to the pre selected sites.
•They are engineered vectors, which retain drug inside or
onto them either via encapsulation and/ or via spacer moiety
and transport or deliver it into vicinity of target cell.
Pharmaceutical carriers :
Polymers
Microcapsules
Microparticles
Lipoproteins
Liposomes
Micelles
10. STRATEGIES OF DRUG TARGETING
1) Passive Targeting :
• Drug delivery systems which are targeted to
systemic circulation are characterized as Passive
delivery systems.
• In this technique drug targeting occurs because of the
body’s natural response to physicochemical
characteristics of the drug or drug carrier system.
11. 2) Inverse Targeting :
•In this type of targeting attempts are made to avoid
passive uptake of colloidal carrier by RES (Reticulo
Endothelial Systems) and hence the process is referred
to as inverse targeting.
•To achieve inverse targeting, RES normal function is
suppressed by pre injecting large amount of blank
colloidal carriers or macromolecules like dextran
sulphate
•Thisapproach leads to saturation of RES and
suppression of defence mechanism. This type of targeting
is a effective approach to target drug(s) to non-RES
organs.
12. 3)Active Targeting :
• In this approach carrier system bearing drug
reaches to specific site on the basis of
modification made on its surface rather than
natural uptake by RES.
• Surface modification technique include coating of
surface with either a bioadhesive, nonionic
surfactant or specific cell or tissue antibodies (i.e.
monoclonal antibodies) or by albumin protein.
3 Types
o First order targeting (organ compartmentalization).
o Second order targeting (cellular targeting).
o Third order targeting (intracellular targeting).
13. 4)Ligand Mediated Targeting : Achieved using
specific mechanisms such as receptor dependent uptake of
natural LDL particles and synthetic lipid microemulsions
of partially reconstituted LDL particles coated with the
apoproteins.
5)Physical Targeting :
•In this type of targeting some characteristics of
environment changes like pH, temperature, light
intensity, electric field, ionic strength small and even
specific stimuli like glucose concentration are used to
localize the drug carrier to predetermined site.
•This approach was found exceptional for tumour
targeting as well as cytosolic delivery of entrapped drug or
genetic material.
14. 6) Dual Targeting :
• In this targeting approach carrier molecule itself
have their own therapeutic activity and thus
increasethe therapeutic effect of drug.
• For example, a carrier molecule having its own
antiviral activity can be loaded with antiviral drug and
the net synergistic effect of drug conjugate was
observed.
7) Double Targeting :
• Temporal and spatial methodologies are combined
to target a carrier system, then targeting may be
called double targeting.
• Spatial placement relates to targeting drugs to
specific organs, tissues, cells or even subcellular
compartment. whereas temporal delivery refers to
controlling the rate of drug delivery to target site.
15. TYPES OF TARGETED DRUG DELIVERY SYSTEM
Nano Tubes : They are hollow cylinder made of
carbon, atoms which can be filled and sealed for
potential drug delivery.
Application : Cellular scale needle for attaching drug
molecule to cancer cells. As an electrode in thermo
cells.
16. Nano wires : The nanowire pinpoint damage from injury
and stroke, localize the cause of seizures, and detect the
presence of tumours and other brain abnormalities.
Application : Technique has potential as a treatment for
Parkinson's and similar diseases.
17. Nanoshells : Nanoshells are hollow silica spheres
covered with gold. Scientists can attach antibodies to
their surfaces, enabling the shells to target certain
shells such as cancer cells.
Application : Technique has potential for targeting
cancerous drug.
18. Quantum dots : Quantum dots are miniscule
semiconductor particles that can serve as sign posts of
certain types of cells or molecules in the body.
Application : Technique has potential for targeting
cancerous drug.
19. Nano pores : Engineered into particles, they are holes
that are so tiny that DNA molecules can pass through
them one strand at a time, allowing for highly precise
and efficient DNA sequencing.
Application : Potential in genetic engineering
and bio technology.
20. Gold Nano : Particle Scientist uses gold nanoparticle to
develop ultrasensitive detection system for DNA and
protein markers associated with many forms of cancer,
including breast prostrate cancer.
Application : In cancer Treatment and Genetic
engineering.
21. Dendrimers : Dendrimers precisely defined, synthetic
nanoparticles that are approximately 510 nm in diameter.
They are made up of layers of polymer surrounding a
control core. The dendrimers surface contains many
different sites to which drugs may be attach.
Application : In gene transfection, medical imaging
22. Liposomes : Liposomes are simple microscopic vesicles
in which an aqueous volume is entirely composed by
membrane of lipid molecule various amphiphelic
molecules have been used to form liposomes. The
drug molecules can either be encapsulated in aqueous
space or intercalated into the lipid bilayers The extent
of location of drug will depend upon its physico-
chemical characteristics and composition of lipids.
Hydrophilic
Hy Hydrophobic
23. Niosomes : Niosomes are nonionic surfactant vesicles
which can entrap both hydrophilic and lipophilic drugs
either in aqueous phase or in vesicular membrane made up
of lipid materials It is reported to attain better stability
than liposome’s. It may prove very useful for targeting the
drugs for treating cancer, parasitic, viral and other
microbial disease more effectively.
24. Ufasomes : These are bilayer structures formed by
using single chain unsaturated fatty acids.
Pharmacosomes: The term pharmacosome comprises of
two main parts Pharmacon (active principle) and some
carriers postulated that amphipathic drug can self
assemble to form vesicle and these vesicles are termed
as pharmacosomes. Drug covalently bound to lipid may
exist in a colloidal dispersion as ultrafine, micelles or
hexagonal aggregates which are known as
pharmacosomes.
25. Virosomes : Virosomes are immuno modulating
liposomes consisting of surface glycoprotein of
influenza virus (immune stimulating reconstituted
influenza virosome) muramyl dipeptide etc. Virosomes
must be target oriented and their fusogenic
characteristics could be exploited in genome grafting and
cellular micro injection.
26. A. Interaction of the virosomes with cell surface recepters.
B. Release of the encapsulated drug molecules in the target cell.
Targeted drug deliverysystem
27. Cubosomes : Cubosomes are liquid crystalline phase
forming small cubic particles suitable for injection.
Nanocrystals : Nanocrystal is any Nano material with at
least one dimension ≤ 100nm and that is single
crystalline. More properly, any material with a dimension
of less than 1 micrometre, i.e., 1000 nanometers, should be
referred to as a nanoparticle, not a Nanocrystal. For
example, any particle which exhibits regions of
crystallinity should be termed nanoparticle or nanocluster
based on dimensions.
28. Nanobots : Nanorobotics is the technology of creating
machines or robots at or close to the microscopic scale
of a nanometer (10−9meters). More specifically,
nanorobotics refers to the still largely hypothetical
nanotechnology engineering discipline of designing and
building nanorobots, devices ranging in size from 0.1-10
micrometers and constructed of nano scale or molecular
components.
29. Transferosomes : A transferosomes, in functional terms,
may be described as lipid droplets of such deformability
that permits its easy penetration through the pores much
smaller than the droplets size.
•Transferosomes is a supramolecular entity that can pass
through a permeability barrier and there by transport
material from the other site.
•These are more elastic than standard liposomes.