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

2. Biopharmaceutical

              -Low absorption

              -High-membrane bounding

              -Biological instability

3. Pharmacokinetic / Pharmacodynamic

              -Short half-life

              -Large volume of distribution

              -Low specificity

4. 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

2. 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

3. 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

4. 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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