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STIMULI SENSITIVE

DRUG DELIVERY
SYSTEM

PRESENTED BY:
Puja Kumari (Bph/10010/15)
Harish Kumar (Bph/10011/15)
Dilshad Shahid (Bph/10012/15)
• These are smart, intelligent, environmental sensitive polymeric systems showing
response in specific environment related to certain stimulus.

• They provide better localization of the systems in desired biological compartment.

• They also provide controlled release of drugs at the desired pathological site.

• Upon application of counter trigger, they have the ability to come back to their
original physical state.
The triggers can be:

External triggers such as electric field, magnetic field, ultrasound,


electromagnetic radiation or temperature, that can be used to turn on or off, the
drug release from the carrier.

Internal triggers – The internal environment of the system in which the drug
delivery system is induced such as ph, temperature, ionic environment, proteins,
carbohydrates.
Fig.:
Various types of stimulus are:

Physical stimuli: Chemical Stimuli:

• They usually modify the energy level of the • They modulate the molecular interactions –
polymer/solvent system. Example: light, between polymer and solvent molecules, or
temperature, ultrasound, etc. between polymer chains.

Biological Stimuli:

• Relate to the actual functioning of molecule,


enzymatic reactions, receptor recognition of
molecules
Fig.: Types of stimuli
Mechanism of action

Conformational changes of
the polymer.

This results in the release of the


drug molecule from carrier or
contribute to its retention within
carrier molecule.
Alter packaging
charachteristics.

Influence the associative


forces between the carrier
and drug molecule.
Systems used as Stimuli Sensitive Systems:

a. Hydrogels: E.g. Polymeric blend of PVA and Gelatin


– Temperature sensitive hydrogels
– pH-sensitive hydrogels
– Electric signal-sensitive hydrogels
– Ion-sensitive hydrogels
– Glucose-sensitive hydrogels
– Light-sensitive hydrogels

b. Interpenetrating polymeric network (IPN)

c. Polymeric nanocomposites: E.g. Polymeric blend of PVA & GUAR GUM using
nanoclay as filters

d. Microneedles & Mononeedles: These are prepared with grafted copolymers


pH-activated DDS

This type of chemically activated system permits targeting the delivery of drug only in
the region with selected pH range.
Categorization of stimuli-responsive polymers

1. Linear Polymeric Chains: Polymers under this category undergo a reversible


collapse after the application of an external stimulus. If stimulus induce an increase
in hydrophilic interaction, the polymer swells.
On the contrary, if stimulus promotes the shift to greater hydrophobicity, the
polymer chain collapse and precipitate out of the solution. E.g.: gums, mucilage
precipitate out in organic solvents like ethanol.

2. Cross linked gels: More cross linking results in decreased swelling and deswelling.
The hydrogels responds rapidly to small changes in pH and temperature and has
been shown to also respond to a change in light intensity, ionic strength, magnetism,
inflammation, ultrasound and certain biochemicals (e.g. Glucose,

3. Chain absorbed or surface grafted form: Such phenomenon depends on the


changes produced at the interface between polymer chains and the environment.
When a polymer reversibly swells or collapses on a surface it converts the interface
from hydrophilic to hydrophobic and vice versa.
This occurs when the collapsed hydrophobic macromolecules aggregate and form a
separate phase.
Factors responsible for Response in a polymer

• The presence of destruction of secondary forces (hydrogen bonding, hydrophobic


effects, electrostatic interactions, etc.), simple reactions (e.g., acid-base reactions)
of moieties linked to the polymer backbone, osmotic pressure differences.

• Dramatic alteration in the polymeric structure, such as degradation of polymers


upon the application of a specific stimulus by bond breakage in the polymer
backbone or by cross linkage groups.
Design of stimuli-responsive systems containing polymers

Using responsive polymer Combining a polymer with a


responsive compound where the
polymer will serve only as a
template or carrier for that
compound.
Optimization and Evaluation of Stimuli responsive systems:

1. Swelling Tests:

Dry samples in de-ionized water at different temperature, ph and various ionic


concentration are to be placed and Equlibrium Degree of Swelling (EDS) is
calculated using the following:

EDS(%) = [Ws-Wd/Wd] * 100

where,
Ws is the swollen weight, &
Wd is the dry weight of the films at time at time t.
Optimization and Evaluation of Stimuli responsive systems:

2. Dye absorption test

• Certain concentration of Congo red solution is to be prepared and the absorbance


of the prepared solution is to be recorded on UV-Vis Spectrophotometer.

• Polymeric samples are then allowed to get soaked in prepared Congo red solution
and left for 24 hours.

• After the duration the absorbance of the solution after swelling of polymer is
recorded
3. Oscillatory Test

The influence of pH pulses are being tested on the polymeric devices and
optimization is to be done based on the systems which shows superior curve for a
prolonged period of time.
Applications:

1. Tissue adhesion prevention material


2. Anticancer drug carrier
3. Immunoassay
4. Wound dressing material
5. Controlled insulin delivery
6. Vector gene delivery
7. Tissue engineering
8. Implantable drug delivery
9. Enhanced gene expression