Hydrogel Biodegradable Polymers: Acrylamide Derivative/Chitosan/PEG/PLA&PLGA

Hydrogels are cross-linked polymers with the ability to swell in an aqueous medium.
Hydrogels have been attractive to the pharmaceutical industry for several reasons including the
controlled release of an active pharmaceutical ingredient, disintegration of dosage forms,
protecting an active and to increase the product life cycle management. There are a lot of
chemical structure and crosslinking methods in hydrogels for various applications in
pharmaceutical and biomedical fields. An understanding in hydrogels characteristics is important
for the innovation for pharmaceutical development.
1. Introduction of Hydrogel
Hydrosol is a product of the polymer-liquid interaction where the polymer is hydrophilic
and the liquid is water. The dissolution of a hydrophilic polymer in water can be prevented by
adding cross links via either a physical or a chemical process. A cross linked hydrosol is called a
hydrogel and can only swell in the surrounding liquid to a certain swelling ratio, depending on
the number of crosslinks.
There are two types of hydrogels, which are physical and chemical gel. Physical gels
achieved via utilizing physical processes such as association, aggregation, crystallization,
complexation, and hydrogen bonding. On the contrary, chemical hydrogel achieved via utilizing
chemical processes, for example chemical covalent crosslinking. While physical hydrogels are
reversible due to the conformational changes, chemical hydrogels are permanent and irreversible
as a result of configurational changes.

(a)
(b)
(c)
(d)
Figure 1. (a-c) Physical hydrogel crosslinked : (a) Polymer-polymer complexation, (b) chain aggregation, (c)
hydrophobic association; (d) Chemical hydrogel crosslinked

Hydrogels classified based on their interaction with the surrounding environment. The
important factors that trigger a hydrogel response are pH, temperature, and liquid composition of
swelling medium. Hydrogels responsive to their surrounding environment are:
pH: For ionic hydrogel, with increase in pH, swelling increases in anionic hydrogel and
decreases in cationic hydrogel. Nonionic hydrogels are almost insensitive to pH changes
Temperature: If the hydrogel can form hydrophobic association and chain aggregation, with
increase in temperature, solubility decreases in cellulose derivative and increases in
hydrocolloids. The response of the hydrogel to temperature change can be either direct or
inverse.
Composition of the swelling medium: The hydrogel response would be dramatic if the
swelling medium contains salt and a non-solvent. With increase in concentration of non-

solvent, salts, as well as salt valence, swelling decreases sharply in ionic hydrogels and
swelling decreases moderately in nonionic hydrogels.

(a)
(b)
(c)
Figure 2. Hydrogel swelling and hydrosol solubility dependence on (a) temperature, (b) pH, and (c) nonsolvent
concentration

Hydrogels are generally characterized by their ultimate capacity to absorb liquids (swelling
thermodynamics), the rate at which the liquid is absorbed into their structure (swelling kinetics),
as well as their mechanical property in wet or hydrated state (wet strength). The crosslink density
and the structural integrity (porosity, pore size and its distribution) have the most significant
effect amongst factors affecting the hydrogel properties.
2. Hydrogels in Pharmaceutical Applications
2.1. Polyacrylamide Derivative, PLA, PLGA, PEG as Inverse Thermoresponsive
Hydrogels
The solubility and swellability of the hydrogels containing hydrophobic groups and
segments is dependent on the temperature of the swelling medium. Polyacrylamide derivatives
and PEG display reverse temperature sensitivity. These are soluble in water at low temperature
and become insoluble when temperature rises. This behavior is a result of a delicate balance
between the hydrogen bonding and hydrophobic interactions, which depends on temperature.
The transition temperature at which a water soluble polymer becomes insoluble is called the
lower critical solution temperature (LCST), below which, the hydrogen bonding and above
which, hydrophobic association prevails.
In subcutaneous or parenteral drug delivery, a solution dosage form containing a drug and a
thermosensitive polymer are injected into the patients body at room temperature. The polymer
part of the dosage form then starts to gel at a higher body temperature.
In hydrogels based on acrylamide derivatives, the thermosensitive property of these
hydrogels was shown to be manipulated by changing the molar ratio of the two monomers. The
release of the drug was found to be clearly dependent on temperature and pH.
Two polyesters, PLA and PLGA, as hydrophobic B-blocks of triblock copolymers have been
shown to provide outstanding biodegradability, a higher gelation temperature, and extended
release profiles for hydrophobic drugs. Photo-crosslinked PLA-PEG-PLA nanogels served as a
promising carrier for a hydrophobic drug.
In PEG-Based Hydrogels, an aqueous solution of PEGPLGAPEG triblock copolymers at
low molecular weight and specific composition has been shown to become gel at the body
temperature. A thermoreversible and photopolymerizable gel paving system based on PEGlactide hydrogels has been outlined, for example to reducing thrombogenicity by limiting
deposition of cells and proteins on certain area of the body. PEG-PLGA-PEG hydrogels were
soluble in water at lower temperatures and gelled at higher temperatures. Gelation occurred

based on micellar growth/tight-packing with increasing temperature. With further increase in

temperature, a sol-gel phase transition occurred due to micellar structure breakdown and
dehydration of PEG and PLGA blocks.
2.2.

Chitosan as pH-Responsive Hydrogels

Some of the hydrogels have a pH sensitive properties. One of them is chitosan based
hydrogel. Enteric coated multiparticulate chitosan hydrogel beads with pH-sensitive property
have been reported as potential orally administrable drug carriers for site specific colon delivery.
Based on examination, the hydrogel swelling was higher in basic medium and significantly
higher swelling capacity in alkaline, than in acidic environment, and the release of the drug was
faster in normal pH than acidic pH. The chitosan hydrogel also showed a good mechanical
strength in its hydrated wet state, claimed to be nontoxic and offered a prolonged release.
2.3. Chitosan as Natural Polymer Based Hydrogels
Hydrocolloids or hydrocolloid hybrids can be used to modified rheological properties of
the drug solutions, dispersions, or emulsions. They are also well established as food ingredients
in nutraceutical industries. Owing to their attractive solution properties, molecular weight,
structure, and availability, various hydrocolloids have been added to the list of pharmaceutical
excipients.
Chitosan, an animal extract gum, has been tested as a taste masker, dietary fiber, drug
delivery matrix, protein and peptide delivery platform, disintegrant, absorption enhancer of
macromolecular drugs, and used in emulsion-like solutions and creams, mucoadhesive delivery,
microparticle formation, local or systemic delivery of drugs and vaccines, and for biomedical
and cosmetic applications.
Using rheological tests, the chitosan gel was proved to be stable when loaded with some
drugs, but loses its stability with the others. As the tablets coat, the release rate of tablet was
decreased with increasing the amount of coated chitosan and increased with decreasing the
chitosan molecular weight. The study shows that chitosan hydrogel may be a promising site
specific carrier for drugs to control vascularization.
2.4. Acrylamide Based Hydrogel as Nonionic Synthetic Hydrogels
Nonionic synthetic hydrogel is hydrogel that does not carry functional groups, and hence
they are not sensitive to the pH of the swelling medium. As a result, their swelling will be only
affected by the polymerliquid interaction forces, which determine the polymer solubility in the
liquid medium. Owing to the lack of electrostatic forces that operate in the pH sensitive
hydrogels, these hydrogels swell to a limited extent. One of the nonionic synthetic hydrogel is
acrylamide based hydrogel.
2.5. Acrylamide In Preparation Of Macroporous Hydrogels
Acrylamide have already been use in preparation of super porous hydrogel. This is the
hydrogel with porosity in its structure in an effort to to change the release properties of a typical
hydrogel. The pores inside the hydrogel structure can be either isolated or interconnected. While
both can offer a faster absorption and release compared to the conventional nonporous hydrogels,

the latter offers a much faster absorption and release. Besides, the equilibrium swelling capacity
of these hydrogels can be reached in seconds or minutes regardless of their size in the dry state.
Hydrogels in general and porous hydrogels in particular suffer from weak mechanical strength in
their wet or hydrated state. Alternatively, various concentrations of different salts can be used to
manipulate the hydrogel mechanical properties. These hydrogels have so far been investigated as
a controlled release platform for proteins, as a gastroretentive platform to enhance bioavailability
of the drugs with narrow absorption window as well as a tablet superdisintegrant.
3.

Hydrogel Products
Besides of the uses of hydrogel that have been mentioned in the previous section, there are
several other products that made from hydrogel. Those products are used for the pharmaceutical
and cosmetic purposes. Some of them are hydrogel implants, hydrogel inserts, osmotic devices,
osmotic implants, osmotic tablets, tissue expanders, and contact lenses.
4.

Conclusion
There are a lot of hydrogel biodegradable polymers. Desirable hydrogel properties for a
given application can be achieved by selecting a proper hydrogel material, crosslinking method,
as well as processing techniques. Factors that can affect the hydrogel are pH, temperature, and
the swelling medium concentration. There are a lot of hydrogels type, and each of them have its
own characteristics and function. Acrylamide, PGE, PLA, and PLGA based hydrogel have a
thermo sensitive properties. Chitosan, as natural polymer based hydrogel, is pH sensitive.