Targeted drug delivery systems (TDDS)

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

  1. Pharmaceutical

              -Drug
instability in conventional dosage form

              -Solubility

  1. Biopharmaceutical

              -Low
absorption

              -High-membrane
bounding

              -Biological
instability

  1. Pharmacokinetic
    / Pharmacodynamic

              -Short
half-life

              -Large
volume of distribution

              -Low
specificity

  1. 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

  1. 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

  1. 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

  1. 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

  1. 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

 

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