stimuli responsive polymers

1. Smart polymersMaryam Kazemi
Pharm .D . Ph.D Student of Pharmaceutics
Shiraz University of Medical Sciences

2. Introduction to smart polymers
• Smart polymers or stimuli-responsive polymers undergo large reversible
changes, either physical or chemical , in their properties as a consequence
of small environmental variations.

4. Temperature-responsive polymers:
• The three main classes of temperature responsive polymers are:
1. shape-memory materials
2. liquid crystalline materials
3. responsive polymer solutions

6. LCST & UCST
• When the phase separation occurs at an elevated temperature, this is referred to as
lower critical solution temperature (LCST) transition
• while the reversed phase behavior is known as upper critical solution temperature
(UCST) transition.

7. Types:
• TRP which shows UCST
• One phase above certain temp
• Phase separation below it
• TRP which shows LCST
• Monophasic below a specific temp
• Biphasic above this temp
 Find applications again as biomaterials mostly

8. Key types of temperature-responsive polymers in
aqueous solution
• Poly(acrylamide)s and poly(vinyl amide)s:
• The most commonly studied and first reported thermoresponsive polymer
in aqueous solution is poly( N -isopropylacrylamide) (PNIPAM).

9. • both PNIPAM and PVCL have been reported to be similarly biocompatible
• The first established LCST is 32oC for poly(N-isopropylacrylamide) (PNIPAAm)
in water solution
• making them ideal candidates for biomedical applications.
• In regard to the very similar properties of both polymers, it is quite surprising
that PNIPAM is considered to be the gold standard of thermoresponsive
polymers, especially for biomedical applications, and that PVCL has never reached or
even come close to such a status.

10. Poly(oligo ethylene glycol
(meth)acrylate)s(POEG(M)A)s
• Similar to PNIPAM and PVCL, multiresponsive POEG(M)As can be
obtained by the incorporation of comonomers that respond to other stimuli,
such as pH or UV-irradiation.
• interpenetrating polymer networks (IPNs). The absence of chemical bonds
between the polymer chains allows a combination of the properties of each polymer and, sometimes, a
synergistic effect on the whole properties of IPN s is obvious

11. UCST polymers
• Thermoresponsive polymers with UCST behavior in water are quite
rare.especially in comparison to the rather generally observed LCST
behavior.
• The best known type of polymers with UCST behavior in water are
the so-called poly(betaine)s, which are zwitterionic polymers
comprising both positive and negative charges in every repeat unit

15. REGEL® DEPOT TECHNOLOGY
• ReGel® is one of MacroMed's proprietary drug delivery systems.
• copolymer of poly (lactide-coglycolide)-poly (ethylene glycol) – poly (lactide-coglycolide)
(PLGA-PEG-PLGA) in phosphate buffer saline. (Negative thermoresponsive)this polymer is
sutable for hydrophilic large molecule drug delivery and lypophilic molecules.
• Thermally reversible gelling materials, such as ReGel®, are a unique class of compounds
being developed for parenteral delivery .

16. • MacroMed's first product, OncoGel®, is supplied as afrozen formulation of paclitaxel in
ReGel® and is entering Phase II trials.
• CytorynTM is MacroMed's immunomodulatory localized peri-tumoral/intra-tumoral
delivery system based on a combination of lymphokine interleukin 2 (IL-2) in ReGel®.

17. pH-responsive polymers:
• pH-sensitive polymers can be defined as polyelectrolytes that include in their
structure weak acidic or basic groups that either accept or release protons in response to a
change in the environmental pH.
• The acidic or basic groups of these polyelectrolytes can be ionized just like acidic or basic groups of monoacids or
monobases; however, complete ionization of these systems is
more difficult due to electrostatic effects exerted by other adjacent ionized groups.
• For example enteric polymers have been used as coatings of tablets for this purpose, examples of which include
cellulose acetate butyrate and cellulose acetate phthalat .
these polymers are insoluble at low pH environments, (e.g., the stomach),
however they are soluble in the less acidic regions of the gastrointestinal tract.

18. • A polyelectrolyte is a macromolecule that can dissociate to give polymeric
ions when dissolved in water or other ionizing solvents.
• Because of the repulsion between charges on the polymer chain, the system
expands when it is ionized in a suitable solvent. However, if the solvent prevents
ionization of the polyelectrolyte, the dissolved chain remains in a compact, folded state.

19. • There is a highly promising role of pH-responsive polymer systems for drug
and gene delivery in the future.
• Typical examples of pH-sensitive polymers with anionic groups are
poly(carboxylic acids) as PAA or poly(methacrylic acid) (PMA) and
polysulfonamides
Poly acrylic acid (PAA), poly vinylacetate diethylaminoacetate , polyethylene
glycol (PEG)

20. Gene carriers:
• Gene carriers: The positively charged polymer-DNA complexes enter the
cytoplasm by binding to the negatively charged cell membrane and endocytosis.
• Due to their buffering capacity between pH 5.0 and 7.2, the endosome is ruptured
by the increased osmotic pressure after acidification of the endosome, and the
internal contents are released.
• Therefore, cationic polymers can efficiently deliver DNA into the cytoplasm
without the help of any colipids as a liposomal compartment.

21. Biosensors
• the most popular applications of pH-sensitive polymers is the fabrication of insulin
delivery systems for the treatment of diabetic patients.
• When there is a rich glucose environment, such as the bloodstream after a meal, the
oxidation of glucose to gluconic acid catalyzed by glucose oxidase (GluOx) can lower
the pH to approximately 5.8. This enzyme is the most widely used in glucose sensing,
and makes possible the use of different types of pH-sensitive HGs for modulated insulin delivery.

22. Photo-responsive polymers:
• Among all the available stimuli light has recently attracted much attention since the
stimulus can be localized in time and space and it can also be triggered from outside the
system.
• Moreover, most of the photochemical processes involved do not require additional
reagents, and by-products are limited in most of the cases.
• The irradiation parameters, such as light intensity and wavelength and irradiation time,
can easily be modulated to adequately comply with the system Photo-responsive
polymers undergo a change in their properties in response to a light stimulus.

23. • Different molecular properties can be light-regulated, including :
• 1.conformation
• 2 . polarity
• 3 .amphiphilicity
• 4 .charge
• 5. optical chirality
• 6 .conjugation
• The light-induced molecular change is reflected in a macroscopic change of material
properties like shape (i.e., contraction or bending), wettability, solubility, optical
properties, conductivity, adhesion and so on.

25. • photo-responsive polymers (PRPs), it is very important to know what type of
photo-responsive moieties is introduced in the polymer and what is the response of
these moieties to a light irradiation. The nature of the photochemical reaction is thus the key parameter for
a rational design of photo-responsive materials.
• Several photosensitive moieties, such as onitrobenzyl esters, may undergo an
irreversible transformation during the irradiation whereas others can react reversibly (e.g.azobenzenes)
• A second parameter that influences the targeted application is the location of the
photo-responsive moiety in the copolymer

26. Applications of PRPs in Solution
• The main envisioned application of PRPs in solution is light controlled
delivery with micelles since light can penetrate to a certain extent into the
skin. This characteristics of light can be employed to deliver active
molecules (drugs) in a precise area of the body.
• With this idea in mind, the simplest design consists of a block copolymer
micelle containing the drug encapsulated into a photo-responsive
hydrophobic micellar core.

27. • Encapsulated nanoparticles into the onitrobenzyl-containing core of aqueous
block copolymer micelles loaded with model molecules The accordingly loaded
micelles were exposed to NIR light at 980 nm and the photons emitted at λ=350
nm by the up-converting nanoparticles were used for the irreversible
photocleavage of the o-nitrobenzylesters. This process thus led to the disruption
of the micelles and the release of the initially encapsulated payloads.

28. • By introducing a light-sensitive chromophore (e.g., trisodium salt of copper
chlorophyllin) to PNIPAM hydrogels, visible light-responsive hydrogels
were prepared When light is applied to the hydrogel, the chromophore absorbs
the light which is dissipated locally as heat by radiationless transitions, increasing
the ‘local’ temperature of the hydrogel. Interestingly, this temperature increase alters
the hydrogel swelling behavior.

29. Magnetically responsive polymer gels and
elastomers:
• .Molecular magnets are systems where permanent magnetization
and magnetic hysteresis can be achieved as a purely one-molecule
phenomenon.
These molecular magnets belong to a field that is still at an early
stage of development.
Their magnetic properties appear at extremely low temperatures
and the magnetic response is rather weak

31. • Superparamagnetic iron oxide nanoparticles (SPIONs) show a great promise for
a wide specter of bioapplications, due to their characteristic magnetic properties
exhibited only in the presence of magnetic field.
• Their advantages in the fields of magnetic drug targeting and imaging are well
established and their safety is assumed, since iron oxide nanoparticles have already
been approved for in vivo application, however, according to many literature
reports the bare metal oxide nanoparticles may cause toxic effects on treated cells

32. Enzyme-responsive polymers:
• Enzyme-responsive polymers are unique in their ability to interact with
biological surroundings through mechanisms that enable dynamic responses
by signal amplification under constant conditions.

33. • For biological applications, enzymatic stimuli have further advantages. As
they are already present in the biological environment, they are able to
operate under the required conditions and do not have to be added
externally,Currently, enzyme-responsive polymers can be placed in one of four
classes:

38. Thanks for your attention