Introduction to NDDS

Drug Delivery

Conventional Controlled

Enteral Sustained

Extended
Parenteral
Site-specific
Other
Pulsatile
Limitations of conventional DDS
1. Drugs with short half-life requires frequent administration, which
increases chances of missing dose of drug leading to poor patient
compliance.
2. A typical peak-valley plasma concentration-time profile is obtained
which makes attainment of steady state condition difficult.
3. The fluctuating drug levels may lead to precipitation of adverse
effects especially of a drug with small therapeutic index, whenever
overmedication occurs.
4. The unavoidable fluctuations of drug concentration may lead to
under medication or over medication.
In order to overcome the drawbacks of conventional drug delivery
systems, several technical advancements have led to the
development of controlled drug delivery system that could
revolutionize method of medication and provide a number of
therapeutic benefits.
Need for NDDS
 The method by which a drug is delivered can have a
significant effect on its efficacy.

 Some drugs have an optimum concentration range

within which maximum benefit is derived, and
concentrations above or below this range can be toxic or
produce no therapeutic benefit at all.

 On the other hand, the very slow progress in the efficacy

of the treatment of severe diseases, has suggested a
growing need for a multidisciplinary approach to the
delivery of therapeutics to targets in tissues.

 From this, new ideas on controlling the

pharmacokinetics, pharmacodynamics, non-specific
toxicity, immunogenicity and efficacy of drugs were
generated.
Need for NDDS
 These new strategies, often called Novel drug
delivery systems (NDDS), are based on
interdisciplinary approaches that combine
polymer science, pharmaceutics, bioconjugate
chemistry, and molecular biology.

 To minimize drug degradation and loss, to

prevent harmful side-effects and to increase
drug bioavailability and the fraction of the drug
accumulated in the required zone, various drug
delivery and drug targeting systems are
currently under development.
 Targeted DDS
8

 Drug targeting is the ability of the drug to accumulate

in the target organ or tissue selectively and
quantitatively, independent of the site and methods of
its administration.

 Ideally, under such conditions, the local concentration

of the drug at the disease site(s) should be high, while
its concentration in other non-target organs and
tissues should be below certain minimal level to
prevent any negative side-reactions.
 Advantages
9

 The following advantages of drug targeting are evident:

(a) Drug administration protocols may be simplified;

(b) Drug quantity required to achieve a therapeutic effect

may be greatly reduced as well as the cost of therapy;

(c) Drug concentration in the required sites can be sharply

increased without negative effects on non-target
compartments.
 Concept of targeting
 Targeting of drugs offers enormous advantages but is equally
10
challenging.

 A better understanding of the physiological barriers which a drug

needs to overcome should enable the pharmaceutical scientists to

develop successful design of targeted drug delivery systems.

 Main hurdles to drug targeting include physiological barriers,

biochemical challenges to identify and validate the molecular

targets and the pharmaceutical challenges to devise appropriate

techniques of conjugating targeting ligands to the systems.

 The challenge in drug targeting is not only the targeting of drug to

a specific site but also retaining it for the desired duration to elicit

pharmacological action.
11
Concept of targeting

 An ideal targeted drug delivery approach would not

only increase therapeutic efficacy of drugs but also
decrease the toxicity associated with drug to allow
lower doses of the drug to be used in therapy.

 A vast array of methods, which can further be

classified into two key approaches active and passive
have been explored for targeting drugs by means of
designing innovative systems.
12
Concept of targeting

 Principal schemes of drug targeting currently

investigated in various experimental and clinical
settings include:

1. Direct application of the drug into the affected zone

(organ, tissue); using carriers - Active targeting

2. Passive accumulation of the drug through leaky

vasculature (tumors, inflammation) - Passive
targeting
 Passive targeting
13• Passive targeting refers to the preferred accumulation of a drug
formulation in a particular tissue based on the biophysical
properties, notably size and charge, of the formulation.
• Additionally, special characteristics of certain tissues can lead to
site specific concentration of a drug.
• For example the enhanced permeability of tumor vasculature and
the inadequate lymphatic drainage of solid tumors results in an
accumulation of long circulating particles (e.g. particles shielded
with polyethylene glycol) in tumor tissues.
• Therefore passive targeting can be seen as a method exploiting the
physical and biological characteristics of the drug and the recipient
organism, respectively.
• It is a nonspecific targeting.
14
 Active targeting
 Active targeting means a specific ligand– receptor type
interaction for intracellular localization which occurs only
after blood circulation and extravasations.
 This active targeting approach can be further classified into
three different levels of targeting which are
 1) First order targeting refers to restricted distribution of
the drug carrier systems to the capillary bed of a
predetermined target site, organ or tissue
 2) Second order targeting refers to selective delivery of
drugs to specific cell types such as tumour cells and not to
the normal cells
 3) Third order targeting refers to drug delivery specifically to
the intracellular site of targeted cells e.g. receptor based
ligand mediated entry of a drug complex into a cell by
endocytosis
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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.