Targeted
drug delivery systems
Session objectives
By the end of this session, students will be able to:
• Discuss
concept of targeted drug delivery
• Explain
need for drug targeting
• Explain
objectives of targeted drug delivery system
• Explain
advantages and disadvantages of TDDS
• Describe
approaches for drug targeting
Targeted drug delivery
• Drugs
have long been used to improve health and extend lives
• The
practice of drug delivery has changed dramatically in the last few decades and even greater changes are anticipated
in the mere future
• Biomedical
engineers have not only contributed substantially to our understanding of the physiological barriers
to efficient drug delivery—such as
transport in the circulatory system and drug
movement through cells and tissues
• They
have also contributed to the development of a number of new modes of drug delivery that have entered
clinical practice
• Yet,
with all of this progress, many medications, even those discovered using the most advanced molecular
biology strategies, have unacceptable
side effects due to the drug acting on non-target sites
• Side
effects limit our ability to design optimal medications for many diseases such as cancer, neurodegenerative
diseases, and infectious diseases
•
Method of delivering medication preferentially
–
To the right place in a body
–
At the right time – Right dose
–
For the right time period
Why drug targeting?
• Lack
of drug specific affinity towards a pathological site
• Nonspecific
toxicity and other adverse side effects
• Act
as Magic bullets (selective targeting)
• Drug
targeting includes coordinated 3 components
a) Drug
b) Targeting moiety
c)
Pharmaceutical carrier
Targeted Drug Delivery
System
• It
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
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
Objectives of targeted
drug delivery system
• To
achieve a desired pharmacological response at a selected sites without
undesirable interaction at other sites
• Specific
action of drug
• Minimum
side effects
• Better
therapeutic index
Disease conditions
requiring targeted drug delivery system
• Chemotherapy
in Cancer
• Cardiovascular
diseases
• Inflammatory
conditions
• Immunotherapy
• Site
targeting- colon targeted
• Protein
therapy
• Alzheimer’s
disease
• Parkinson’s
• Infectious
diseases
Reasons for drug
targeting
- 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
Ideal characteristics of
targeted drug delivery
• Biochemically
inert (non-toxic)
• Non-immunogenic
• Both
physically and chemically stable in vivo and in vitro
• Restrict
drug distribution to target cells or tissues or organs
• Should
have uniform capillary distribution
• Controllable
and predictable 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
Advantages
• Toxicity
is reduced by delivering a drug to its target site, thereby 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
• Drug
administration protocols may be simplified.
• Dose
is less compared to conventional drug delivery system
• No
peak and valley plasma concentration
• Selective
targeting to infections cells that compare to normal cells
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 low E.g. As in micelles. Therefore it is difficult to
predict /fix the dosage regimen
Summary
- Targeted
drug delivery is the method of delivering medication–
–
To the right place in a body
–
At the right time, the right dose
–
For the right time period
–
Not to the other places where drug side-effects
may arise
- 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
- The
objectives of targeting are -To achieve a desired pharmacological response
at a selected sites without undesirable interaction at other sites
–
Specific action of drug
–
Minimum side effects
–
Better therapeutic index
- Reasons
for targeting can be
a) Pharmaceutical
–
Drug instability in conventional dosage form
–
Solubility
b) Biopharmaceutical
–
Low absorption
–
High-membrane bounding
–
Biological instability
c) Pharmacokinetic
/ Pharmacodynamic
–
Short half-life
–
Large volume of distribution
–
Low specificity
d) Clinical
–
Low therapeutic index
5.
There are 3 different approaches:
a)
Physical or Mechanical Approach
b)
Biological Approach
c)
Chemical approach
