INTRODUCTION:

Hydrogels are three-dimensional, hydrophilic, polymeric networks capable of absorbing large amounts of water or biological fluids. Due to their high water content, porosity and soft texture, they closely simulate natural living tissue, more than any other class of synthetic biomaterials. Hydrogels are chemically stable as they may degrade and eventually disintegrate and dissolve. Hydrogels are termed as ‘reversible’ or ‘physical’ gels when molecular entanglements and/or secondary forces such as ionic, H-bonding or hydrophobic forces play main role in forming the polymeric network. Physical gels are often reversible and can be dissolved by altering environmental conditions, pH, ionic strength of solution or temperature. They are called as ‘permanent’ or ‘chemical’ gels, when the network of covalent bonds joining different macromolecular chains can be achieved by cross-linking polymers in the dry state.

These gels may be charged or non-charged depending on the nature of functional groups present in their structure. The charged hydrogels usually show variations in swelling due to changes in pH, and undergo changes in shape when exposed to an electric charge. [1- 3]

Chemical hydrogels are commonly prepared in by ‘three-dimensional polymerization’, in which a hydrophilic monomer is polymerized in the presence of a poly functional cross-linking agent, or by direct cross-linking of water-soluble polymers. Polymerization is usually initiated by free-radical generating compounds. such as benzoyl peroxide, 2, 2-azo-isobutyronitrile (AIBN), and ammonium peroxodisulphate or by using UV, gamma or electron beam-radiation.However,three-dimension polymerization often results in materials containing significant levels of residual monomers and therefore purification of these materials has to be performed thoroughly because the unreacted monomers are often toxic and could leach out from the hydrogels continuously. The purification of hydrogels containing residual monomers is typically performed by extraction into excess water, and can take up to several weeks to be completed. [4]

Synthesis of Hydrogel Products: [5-7]

1. Cross Linking Method:

Synthesis of hydrogels by cross linking of readymade water soluble polymers

Fig 1: Synthesis of hydrogels by cross linking

2. Three Dimensional Polymerization Method: Synthesis of hydrogels by three dimensional polymerization,occurs when a hydrophilic monomer is polymerized in the presence of a polyfunctional cross-linking agent.

Fig 2: Synthesis of hydrogels by polymerization

Classification of hydrogel products:

Fig 3: Classification of hydrogels based on various properties

Applications of Hydrogel Products:

Hydrogels are a unique class of materials that are hydrophilic, self-supporting, three- dimensional viscoelastic networks, which allow diffusion and attachment of molecules and cells. These networks can be composed of photopolymers or copolymers, and their structural and physical integrity is due to the presence of cross links, which can be of physical (such as entanglements or crystallites) or chemical (junctions or tie- points) in nature. Based on the nature and on the stability of crosslinking, which depends on various parameters like temperature, ions, or UV radiation), the final hydrogel results in a polymer with specific and peculiar characteristics.

Due the wide spectrum of both chemical and physical characteristics, hydrogels have been extensively used in pharmaceutical and biomedical applications. In the main methods to achieve the hydrogel’s cross-linking are listed and some of the application fields covered by this review are depicted. [8]

· Hydrogels are used for producing contact lenses, hygiene products and wound dressings.

· Commercial uses of hrdrogels include drug delivery and tissue engineering Some examples of methods to crosslink hydrogels and their biomedical applications.

Fig 4: Applications of Hydrogels

Contact lens:

Contact lens comes in direct contact with the eye to correct the vision, an delivers the drug for ophthalmic infections whenever required. There are two major types of contact lens i.e. rigid and soft contact lens. Rigid contact lenses are made with polymer polymethyl methacrylate (PMMA). It has properties like surface wettability, high modulus of elasticity with excellent durability. But it has no oxygen permeability. A hydrogel system based on Poly (2-hydroxyethyl methacrylate) (pHEMA) was the first hydrogel material used to make a contact lens. Poly (vinyl alcohol), polyacrylonitrile, etc. are the hydrophilic polymers that have been investigated for making hydrogel contact lenses. Besides this, silicone and fluorine-based hydrogel contact lens are also investigated. But silicone-based hydrogel contact lenses are one of the most dominant hydrogel materials today. A soft or hydrogel contact lenses has properties like high water content, ability to transfer water and oxygen permeability [9]. Oxygen permeability is a very important characteristic of the proper functioning of the cornea because cornea uses oxygen from the air to maintain its structure, function, and clarity. The oxygen permeability of hydrogel contact lenses is critically related to the water content and thickness of the contact lens. Apart from this, it should be biocompatible, comfort to wear, continuous tear film for clear vision, permeable to ions for maintaining movement, non- irritable and resistant to tear film accumulation. Luminous transmittance and refractive index are the important requirements for making hydrogel as contact lenses.The extended use of conventional hydrogel contact lenses can cause hypoxia on corneal physiology and corneal upintegrity and function. The high oxygen permeability capacity of silicone-based soft contact lens can avoid these types of adverse corneal effects. But silicone-based hydrogel contact lens can also have the potential of causing corneal homeostasis when used over an extended period of time. [10]

Fig 5: Preparation of Hydrogel Contact lens

Wound Dressings:

A wound is a defect or a break in the skin which can result from trauma or medical/physiological conditions. Wounds are usually sub-divided into ‘acute’ or ‘chronic’ wounds. Chronic wounds require dedicated nursing care that represents a significant cost for national health systems. Design of effective dressings relies on an understanding of the healing process, as well as the specific conditions of a patient and the effect that each material used could have on the. Wound healing can be hindered by various factors such as desiccation, infection or abnormal bacterial presence, maceration, necrosis, pressure, trauma and edema. A variety of advanced wound dressings are being developed in the recent times. Wound dressings can also be formulated in the form of hydrogels which are autolytic debridement and rehydrate to soften dry wounds. [11-13]

Tissue Engineering:

Tissue engineering is a more recent application of hydrogels, in which they can be applied as space filling agents, as delivery vehicles for bioactive substances or as three- dimensional structures that organize cells and present stimuli to ensure the development of a required tissue. [14]

Fig 6: Application of hydrogels in Tissue Engineering

Drug Delivery:

Fig 7: Scheme of drug release through a hydrogel membrane in a reservoir system.

Hydrogels are extensively used in drug delivery and play a major role as drug vehicle. In this study commercial products for drug delivery based on hydrogels are discussed on the basis of the administration route. [15-17]

Fig 8: Scheme of drug release from matrix systems.

Topical Delivery:

The topical hydrogels are effectively used to deliver drugs that can help to ease the symptoms of many pathological conditions. The hydrogel usually contain a hydrophilic non-woven fabric sheet and an air-permeable polyethylene film.

Buccal Delivery:

Though many dosage forms are recommended for delivery into the buccal mucosa, such as tablets, patches, sprays, chewing gums, or lollypop systems, a large part of these are affected by leakage into the gastrointestinal tract. Thus, in order to allow the release only across the buccal mucosa, mucoadhesive patches or tablets can be used. Hydrogel-based bio adhesive tablets can control the drug release rate depending on the hydration of the device, which is the driving force for determining its swelling ability. Hydroxypropylmethyl cellulose (HPC), Hydroxyethyl cellulose (HEC), Polycyclic (PA) resins, Carboxymethyl cellulose (CMC), polyvinyl alcohol (PVA), Hydroxypropylmethyl cellulose (HPMC), Chitosan are cellulosic or acrylic polymers having high adhesion performance for prolonged time, even with high drug content are generally used in the formulation of Hydrogels. Commercial product for buccal delivery found in the market, include hydrogels for mouth care and hydration to sustained drug delivery systems to prevent angina. [18]

Biomedicalapplications:

Marine algae are capable of synthesizing Glycosaminoglycan’s (GAGs) and non- GAG’s or GAG mimetic such as sulfated glycan’s. The cell walls of algae are rich in sulfated polysaccharides, including alginate, carrageenan, elven and fucoid. These biopolymers are widely used as algal-derived polysaccharides for biological and biomedical applications due to their biocompatibility and availability. They constitute biochemical compounds that have multi-functionalization, therapeutic potential and immunomodulatory abilities, making them promising bioactive products and biomaterials with a wide range of biomedical applications [19]

Nanocomposite hydrogels for biomedical applications:

Fig 9: Biomedical applications of nanocomposite Hydrogels

Immunotherapy and Vaccine:

A Nano vector composed of peptide-based Nano fibrous hydrogel can condense DNA to result in strong immune response against HIV. HIV infection is presently incurable and has led to the death of more than 30 million. Traditional, vaccines are ineffective and pose potential risks. As a consequence, safe alternatives such as DNA vaccines have attracted great attention as they are easily degraded by DNAses and lysosomes, and injected naked DNA plasmids are poorly distributed and inefficiently expressed; thus, DNA vaccines can only induce modest humoral and cellular immune responses. As such, DNA vaccines must be injected with a delivery system to enhance the immune responses. Some disadvantages limit their further usage, such as toxicity, small amount of antigen loading and decreased biological activity of DNA during complex preparation. [20]

Environmental applications:

Over past the years, nations gradually started to care about environmental issues and pollution. Many governments decided to opt for greener and safer for the environment policies. Water pollution is one of the biggest issues afflicting especially poor areas of Africa, Asia and South America. Thanks to their affinity for water, hydrogels might be used in two different ways to treat water source.

First the matrix can be used as a holder for purifying microorganism. Many interesting studies, on this particular path, were developed by encapsulating microorganisms inside diverse carriers materials. These microorganisms are already used to remove pollutants and chemicals from water resources. The idea is to keep the bacteria inside the network and consequently protect and control the bacteria-colturewhile cleaning the site of depuration. Both synthetic and natural hydrogels were been used. The best working hydrogels in literature appear to be Alginate derived material or alternatively carrageenan and agar. [21]

Bacterial Culture:

As already discussed above, hydrogels can hold inside their matrix a significant number of microorganism for purification of water, for production of biomolecules, or for simple culture of bacteria by themselves.

Indeed, agar is famous as the golden standard substrate for bacterial culture in biotechnological applications. Since it is indigestible by a great number of bacteria and other microorganisms, it provides a perfect environment for their culture on a solid substrate. Different kinds of agar have been studied, each with a potential use for preparation of different kinds of bacterial culture. Among them brucella agar, columbi agar, schaedler agar, or trypicasesoy agar are the most common. [22]

Cosmetic Applications:

The major function of the skin is to protect the body from environmental factors such as microorganisms and UV radiation. Besides it also helps in maintaining the body temperature and body fluid. Hydration of the skin is important in the maintenance of its appearance and texture. Natural aging, due to the genetic factors and photoaging, due to sun exposure serves as major reasons for skin damage apart from climatic conditions and pollution exposure Cosmetics products are used to enhance skin appearance and texture. Lotions, skin cleaners are some of the cosmetic items used for maintaining the body. Nowadays, the cosmetics industries showing more interest in hydrogels due to properties like biocompatibility, elasticity, softness and high water content. [23]

The hydrogel can be used for skin issues such as cellulite, wrinkles, pigmentation, skin hydration and aging. Caffeine-containing bio adhesive hydrogel used for cosmetic applications mainly cellulite or gynoid lipodystrophy. The bio adhesive property of hydrogel helps in releasing caffeine gradually into the skin thereby enhancing skin appearance and texture. The skin permeation of drugs was improved through the hydrogel system, which helps in loosening the skin barrier through skin hydration. In the market, hydrogel products such as face mask, lip mask, under eye pad etc are available for treating skin related issues. Collagen hydrogel by used as a cosmetic product, which helps to regenerate and restore the softness, elasticity and hydration of the skin. This hydrogel is made up of hyaluronic acid and collagen. Hyaluronic acid plays an important role in skin moisture by giving hydration to the skin. [24]

CONCLUSION:

In this review we studied an overview on the development in hydrogel research from simple networks to smart materials. Hydrogels are widely present in everyday products though their potential has not been fully explored yet. These materials have a well-established role in contact lenses, hygiene products and wound dressing markets but commercial hydrogel products in tissue engineering and drug delivery are still limited. Many hydrogel based drug delivery devices have been studied and in some cases even patented, but however many of them have not reached the market. More progress is expected in these two areas [25-27]

Over the past decades, significant progress has been made in the field of hydrogels as functional biomaterials. Biomedical application of hydrogels was initially hindered by the toxicity of cross linking agents and limitations of hydrogel formation under physiological conditions. Emerging knowledge in polymer chemistry and increased understanding of biological processes resulted in the design of versatile materials and minimally invasive therapies. Hydrogel matrices comprise a wide range of natural and synthetic polymers held together by a variety of physical or chemical cross links, with their capacity to embeed pharmaceutical agents in their hydrophilic cross-linked network. Hydrogels form promising products for controlled drug release and tissue engineering. Despite all their beneficial properties, there are still several challenges to overcome for clinical translation.

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Received on 03.08.2020 Revised on 01.09.2020

Asian J. Pharm. Res. 2021; 11(1):23-28.

DOI: 10.5958/2231-5691.2021.00006.X

Product name	Manufacturer	Hydrogel form/Characteristics
Lip patch	Taiki	Hydrogel patch contains sodium hyaluronate and glycerine for moisturizing. Strong adhesion and makes the lips elastic and hydrated
Aloe Vera supple skin hydrogel	Images	Sheet mask contains Hyaluronic acid, glycerol, water etc. Moisturizes, nourishes, smooths the skin and also gives elasticity and firmness to the skin.
Neutrogena® Hydro Boost®	Johnson and Johnson	Face mask contains hyaluronic acid. Provides instant and long lasting moisture to the skin.
Rose soothing hydrogel mask	Moira	Face Mask made with sodium polyacrylate, glycerine, cellulose gum, water etc. with maximum absorption. Soothens and rejuvenates the skin
Collagen Hydrogel	Dr. Derm Professional	Hydrogel contains sea collagen and hyaluronic acid. Nourishes and regenerates the skin of the face.
Advanced Génifique Hydrogel 3k	Lancome Paris	Hydrogel face mask made up of glycerine, polyacrylate-13, water etc. enriched with Bifidus extract. Skin will become moisturized, radiant, smoother and looks healthy glow
Charcoal Hydrogel under eye mask	ELF cosmetics	Under Eye mask contains water, charcoal, seaweed extract, etc. Nourishes and gives a healthy glow to the skin.