TOPIC: SODIUM ALGINATE AND TITANIUM OXIDE BASED HYDROGEL BEADS

AND THEIR SWELLING PROPERTIES

Introduction:

Hydrogels are unsolvable three-dimensional polymer chain networks that swell with water or by

various solution. These are sensitive to certain particular factors such as pH, temperature, and

ions like H+, OH-, CH3COO-, HCO3-, CO3- etc. Antigens, pharmaceuticals, peptides, proteins,

enzymes. Hence, hydrogels are excellent Candidates for the development of intelligent systems

to improve therapeutic efficacy. Hydrogels can be reversibly swollen and dwelled, so they can

hold large amounts of Water. This hydrophilic character arises from the presence of functional groups

such as hydroxyl (-OH), carboxyl (-COOH), amine (-NH 2), and sulfate (SO3H) which make it possible to

absorb water by the hydrogel. Establish connections between network chains It makes the hydrogel

water-insoluble and gives it the correct geometric dimensions.

Swelling of hydrogel Properties are mainly dependent on the external environment such as

temperature, pH, and ions

Concentration can help change the volume of the hydrogel (collapse

or phase transition) [21, 22, 23]. Hydrogels can be made from a variety of natural

and synthetic polymeric materials. Natural polymers with high porosity

Degradable, biocompatible, non-toxic [24]. Therefore, hydrogels made of natural polymers have

been investigated for drug delivery [25]. it is generally

Natural polymers used include collagen, gelatin, hyaluronic acid, fibrin, chitosan, agarose,

and alginates [26, 27]. Among these polymers, alginate is unique in that it becomes ionic

Cross-linking in the presence of divalent cations such as calcium (Ca2+)

Easy synthetic process. Therefore, alginate is one of the most commonly used biomaterials.

Used for drug delivery and tissue engineering. 3. Sensitive/Responsive Hydrogel

Hydrogels that are sensitive to and respond to specific environmental changes

The shape or volume when exposed to certain conditions is considered a stimulus-sensitive

hydrogel. They are (i) sensitive to physical stimuli such as light, pressure, temperature, electric

fields, and magnetism;

fields, ultrasound, (ii) chemical stimuli such as pH, redox, ionic strength, CO2, glucose, and (iii)

Biological stimuli such as enzymes, [24] antigens, glutathione, and DNA. main uses of

Smart hydrogels are summarized in Figure 3a, demonstrating trigger factors for swelling when

sensitive to stimuli.

The hydrogel is shown decisively in Figure 3b.

These stimuli can also be classified as internal or external stimuli based on their source

Application time to hydrogels in vivo. The former includes chemical and biological stimuli

category, physical stimuli belong to the latter category, except for temperature, which could

External or internal stimuli [25]. The terms "smart" or "intelligent" were coined for this.

Hydrogel in the sense that it senses stimuli and responds to them by altering the body

and/or chemical behavior leading to the release of entrapped drugs [26]

3.

Stimuli-Hydrogel responsiveness

An ideal drug delivery system relies on the fact that the drug release profile can do this

Responds to metabolic state and/or physiological fluctuations (Bawa et al., 2009).

Stimulus-responsive polymers are at the forefront of drug delivery technology.

Sensitive to small signs and environmental changes,

Who introduced appropriate changes to the network structure and who

Physiological and chemical properties where appropriate (Grainger, El-Sayed, 2010; Kuckling,

Urban, 2011). In conclusion, responding to stimuli

Hydrogels can respond to stimuli by exhibiting physical or chemical effects

Changes in her behavior, such as dispensing any medicine she has (Gupta et al.

et al., 2002). A key feature of these smart polymers is that they can

Returns to its original state when the sign or stimulus ends and can be reversed

Macroscopic changes (Stuart et al., 2010). Stimuli-responsive hydrogel

It is biocompatible, non-thrombogenic, strong, flexible, and readily malleable. you are not

Not only is it easy to manufacture, but the stability of the drug can be maintained,

It is possible to inject them in vitro to form gels at body temperature (Mahajan,

Agarwal, 2011). Stimuli that cause behavioral changes in these hydrogels

physical stimuli (temperature, ultrasound,

light, mechanical stress), chemical stimuli (pH and ionic strength), and biological stimuli

Stimuli (enzymes and biomolecules) (Fig. 1.2) (Jeong, Gutowska, 2002; Kumar et al.,

2007). of pH-sensitive hydrogels

The pH-sensitive swelling results from ionic hydrogels with charged pendant groups.

Controlled by many factors such as ionic charge, pKa or pKb value of the ionic group, grade

of ionization, hydrophilicity, polymer concentration, and pH of the source medium. under these

Factors, pH, and the nature of the side groups are the key factors controlling the properties of

pH-sensitive hydrogel. Cationic hydrogels such as chitosan and poly(ethyleneimine) [35] swell at

low temperatures.

pH (acidic medium) due to protonation of amino/imine groups. protonated positive charge

Units on the polymer chain cause repulsion and thus swelling. These guys

hydrogels can be used as a delivery or carrier for drugs (antibiotics) to the stomach during

ulceration.

For injectable drug delivery systems. Anionic hydrogels such as carboxymethyl chitosan swell
High pH (basic medium) due to ionization of acidic groups. Negative ionization with this

Charged side groups on the polymer chains cause repulsion, leading to swelling. This property of

Hydrogels can be used for drug delivery at pH 7.4 in the intestine [47]. another novel approach

A successful drug delivery application is the use of polyelectrolyte complexes

(PEC) Hydrogels without toxic covalent crosslinkers. PEC hydrogels are mainly

It consists of two components: (i) a cationic polymer such as chitosan and (ii) an anionic polymer

such as

carboxymethyl Chitosan is stabilized by electrostatic interactions between these opposite charges

mixed with Arino et al. Prepared pH-sensitive PEC hydrogels containing N-trimethyl chitosan

(cationic component) and N-carboxymethyl chitosan (anionic component) to study drug delivery

Dexamethasone profile [48].

1.2.5. Theory and swelling mechanism of pH-sensitive hydrogels

Swelling of hydrogels, when exposed to water/physiological fluids, depends on osmosiThe

hydrophilicity of constituent polymers, the pressure within hydrogels caused by static electricity

Polymer and counterion charges within the hydrogel matrix. Swelling of hydrogel

It consists of three steps: the first is the diffusion of water into the hydrogel network and the

second is the loosening.

The third of the polymer chains upon hydration is the expansion of the hydrogel network.

Polymer chains relax [49,50]. Attraction to hydrophilic and polar water molecules

Groups lead to absorption, which is callprimary-boundund water. This causes the hydrogel to

swell.

The exposed hydrophobic part interacts with water molecules called secondary bonds

water. Additional water moves into the hydrogel under the influence of the osmotic driving force
The elastic contraction force cancels the lateral connection. This additional absorbed moisture is

Called free water, hydrogels reach equilibrium swelling [1]. This equilibrium haThe balance

between elastic recoil force and osmotic pressure of the chain. this is explained

According to Flory and Rehner's theory. According to this theory, swelling is a function of

elasticity.

Polymer chain structure and thermodynamic compatibility between water molecules and

polymers

chain. When stimuli-responsive hydrogels are exposed to certain substances, volume phase

transitions occur.

stimulation [44]. The swelling of ionic hydrogels is mainly controlled by two factors.

Polymers that makeup hydrogels, such as crosslink density, hydrophilicity, and hydrophobicity

Concentration, ionic charge, pKa of acidic side groups, or pKb of basic side groups

group, and (ii) properties of the source medium such as ionic strength, pH, and counterion

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The swelling of hydrogels with acidic or basic side groups on polymer chains depends on this.

For the pH of the surrounding medium for the respective pKa and pKb values of the pendant

group. For anionic networks (e.g. carboxyl, -COOH side groups),

The pH of the surrounding medium is greater than the pKa of the acidic side groups

In polymer chains, ionization of acid groups occurs, leading to the formation of anchors

Negative charges on polymer chains and mobile positive charges in solution. The result there

(i) increased hydrophilicity of the hydrogel, (ii) number of fixed negative charges,

(iii) electrostatic repulsion between chains leading to swelling of the hydrogel network;

and vice versa (when pH is less than pKa). On the other hand, cation networks (e.g.
If the pH of the surrounding medium is lower than the pKb

Protonation (ionization) of the pendant group occurs,

Increased number of fixed positive and mobile negative charges on the polymer chain

solution. Consequently, this causes swelling due to the increased hydrophilicity of (i).

the polymer chains, (ii) the number of fixed positive charges, and (iii) the electrostatic repulsion

between them

chains and vice versa (pH greater than pKb) [26,44]. pH-dependent ionization of

The specific acidic or basic functional groups on the hydrogel strands responsible for swelling

are shown in Figure 1.

Figure 4a.

Stimuli-responsive hydrogels that show reversible temperature-dependent swelling behavior

are termed thermoresponsive hydrogels. Based on their response to temperature,

thermoresponsive

hydrogels are classified as (i) positive thermoresponsive hydrogels like poly(acrylamide) which

swell

above their characteristic upper critical solution temperature (UCST) and vice versa, (ii) negative

thermoresponsive hydrogels like poly(N-methacrylamide) which swell below their characteristic

lower

critical solution temperature (LCST) and vice versa [25,44], and (iii) thermo-reversible

hydrogels like

(poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)) (PEO-PPO-PEO) which

undergo

sol-gel phase transition below and above the critical solution temperature (CST) instead of the
swelling-shrinking transition [13]. The UCST response in poly(acrylic acid) and

poly(acrylamide) is

primarily due to the presence of secondary hydrogen bonding which dominates at low

temperature

and keeps the hydrogel matrix shrunk whereas, with increasing temperature, hydrogen bonds

weaken and the hydrophilic ends become exposed leading to the phenomenon of swelling

[51,52].

The hydrophobic interactions between polymer chains and water are responsible for the LCST

response

of poly(N-methacrylamide). The polymer network becomes more ordered and shrinks/collapses

with

the rise in temperature whereas water molecules become less ordered and are removed from the

polymer network [52,53]. Certain van der Waals forces such as hydrogen bonding and

hydrophobicity

The interaction is involved in the thermoreversible behavior of hydrogels in CST. in solution (sol

shape), there are hydrogen bonds between polar groups in the polymer chain, which is true

Bonding becomes unfavorable in CST, polymer-polymer and water-water interactions dominate,

Dehydration removes water from the hydrogel. This leads to an overall increase in entropy

System shrinkage and concomitant hydrogel shrinkage