The 3-D structure of cross-linked polymer chains extremely proficient in absorbing water are known as hydrogels (HGs). Although HGs have many uses across many industries, the biomedical sector is where they are most beneficial¹^. The occurrence of polar functional groups such as SO₃H, OH, NH₂, COOH, CONH₂, etc. is allowing for the demonstration of such phenomena in HGs². The tendency of HGs to absorb fluids is owing to their engorgement belongings, which are controlled by the aquaphilicity of the binding clusters, the enlargement of the medium, and the sturdiness of the crosslinks.

Crosslinking also helps control water absorption and maintain network structure in the swollen state. Distinguishing belongings such as biodegradability, biocompatibility, polarity, super-absorbency, viscoelasticity, softness, and fluffiness make HGs an important part of biomedical uses³.

2. MATERIALS AND METHODS:

A broad literature was collected from Science Direct, PubMed, Google Scholar, and other journal websites.

3. RESULT AND DISCUSSION:

Composition of Hydrogels (HGs):

HGs are cross-linked polymers categorized into natural, synthetic grafted polymer derivatives or a mixture of them. The HGs are made of natural polymers hence referred to as natural HGs. Reliant on their chemical makeup, natural polymers were distributed into (i) Polysaccharides (chitin, chitosan, cellulose, starch, gums, alginate, and carrageenan), (ii) Biological polymers (nucleic acid and DNA), (iii) Polyamides (collagen), (iv) Polyphenols (lignin), (v) Organic polyesters, (vi) Inorganic polyesters (polyphosphazene), and (vii) Polyanhydrides (poly sebacic acid)⁴.

· Types of Polymers used in making HGs:

1. Water-soluble synthetic polymers: Hydrophilic functional groups, such as ester, amide, or Pyrrolidone, are present in water-soluble synthetic polymers. These polymers are frequently non-toxic and BC. These polymers consist of Polyvinyl Pyrrolidone, polyacrylamide, polyacrylic acid, and polyethylene glycol⁵.

2. Cellulose derivatives: The major component of higher plants is cellulose. Water and other solvents cannot dissolve cellulose. Because of the hydrogen bonds that exist between them, they are insoluble. The pharmaceutical industry, however, makes substantial use of its water-soluble derivatives. The widely employed derivatives are CMC, HPMC, and HEC.

3. Hydrocolloids: Since the majority of gums are hydrophilic, they are frequently used in medicinal operations. Gums can thicken and form gel; the former is good for emulsions and suspensions, whereas the latter is useful for controlled drug administration. Guar gum exhibits thickening, whereas chitosan exhibits gelling. One drawback of gums is that they offer a favorable environment for microbial growth.

4. Natural polymers: Examples of natural polymers include Gelatine, Dextran ⁷, Xanthan Gum, etc.

5. Starch-based polymers: All plants produce and store starch for energy. Small granules ranging in size from 1 to 100 micrometers are readily available. Due to the fact that starch is a biodegradable polymer, it has uses in medicine. Some of the commonly used Polymers are given in Table 1 below.

Biomedical Applications of HGs:

The versatile applications of hydrogels in the drug delivery system are displayed in Fig. 1.

Fig. 1. Applications of Hydrogels in drug delivery system

Wound healing:

The characteristics of chitosan were improved by attaching with constituents to achieve chitosan complexes. These composites render tunable assets that are more highly competent than alone ¹¹. The WH and drug delivery contributed significantly to these modified composites. Chitosan's gelling properties also favorably back the expansion and use of unconsciously stable HGs. Silver nanoparticles (NPs) on the polymer matrix of B. chitosan have improved antimicrobial properties and material stability and have confirmed operative substitutes for the management of skin pathogens and proper wound regeneration ¹².

Tran et al. developed rutin-based chitosan HG as an injectable dressing for WH. They displayed upgraded WH matched to rutin-free HGs ¹³. Yang et al. A succession of HGs was prepared from polar solutions of gelatine and carboxymethyl chitosan by crosslinking at ambient temperature for WH. The resulting HGs indorsed cell adhesion and hasty progression of fibroblasts on the material ¹⁴.

Tissue Engineering (TE):

Laponite, a synthetic nanoclays consisting of nanoplatelet-shaped silicates, has demonstrated remarkable promise in TE. A multi-membrane hydrogel (MMH) based on chitosan was created by Ladet et al. to study the approachability of articular chondrocyte-like cells. The cubicles produced a significant amount of matrix proteins resembling cartilage, aggregated, multiplied, and retained their phenotype ¹⁵.

It is particularly advantageous to use hydrogel scaffolds for TE solicitations since they have appealing qualities for a variety of uses. For instance, HGs enable the inclusion of cells and bioactive compounds and suggest a diversity of mechanical belongings, such as the appropriate stiffness and porosity. Particularly natural HGs are ultimate for TE solicitations because they enhance cell adhesion, degrade inside the system, have inherent biocompatibility, and are non-cytotoxic. For the most efficient regeneration, the hydrogel scaffold, which serves as the extracellular matrix (ECM), can incorporate several growth factor hubs that are tailored to the tissue application and mimic the natural milieu of the tissues. The mechanical characteristics of the scaffold must correspond to those of the underlying tissue ^16,17.

A newly developed therapeutic approach involves engineering cardiac tissues for tissue rejuvenation. Cardio myocytes or stem cells have been created on a cardiac patch that is positioned onto the infarcted spot of the heart, especially using natural HGs, which may help to improve the condition ^18,19. The current developments in cardiac TE have used carbon nanotubes (CNTs), gold NPs (AuNPs), or graphene and its derivatives to nano-functionalize natural HGs ²⁰. Alginate hydrogel is also a good alternative for cardiac TE as it mimics ECM and is BC ²¹²².

Collagen is an extensively employed natural hydrogel for brain repair and neural regeneration. Collagen can be utilized as an injectable scaffold, consenting for the local delivery of neuroprotective soluble factors, encapsulated stem cells with the ability to regenerate tissue or to provide mechanical sustenance for the axons to develop ²³.

Cancer Treatment:

An innovative management strategy for cancer is achieved by stimulating the body's immune responses to eliminate tumors. The realizing the local delivery of immunotherapeutic drugs using HGs based on polymers for cancer immunotherapy ²⁵. The uses of different types of HGs for the treatment of various types of cancers are given in Table 2 below.

Table 2: Applications of HGs in the cancer

Sr. No.	Type of Hydrogel	Type of Cancer	Description	References
1.	Thermosensitive – Hydrogel	Breast Cancer (BC)	Thermosensitive HGs have been used for localized drug delivery in BC. These HGs can change their gel to a sol state in response to temperature, allowing for easy injection and subsequent gelation at the tumor site. This enables the controlled release of anticancer drugs, improving their effectiveness while minimizing systemic side effects.	25
2.	Injectable HGs	Prostate Cancer	Injectable HGs are being investigated as a minimally invasive approach for delivering therapeutic agents to prostate cancer tumors. These HGs injected straight into the tumor site, forming a gel-like matrix that provides sustained release of drugs or encapsulated cells. This targeted delivery system has the potential to progress treatment outcomes and lessen systemic toxicity.	26
3.	pH-responsive Hydrogel	Colon Cancer	pH-responsive HGs have shown promise in colon cancer therapy. These HGs undergo swelling or degradation in alterations in pH, such as the slightly acidic environment found in the colon. This property can be exploited to transport actives explicitly to the colon and improve their therapeutic efficacy. Human colon cancer cells were used in an in vitro cytotoxicity assay, and the findings displayed actives encumbered β-CD-g-Gel/OX-Dex (CHG) demonstrated increased cell suppression matched to the active-only.	27
4.	Stimuli-responsive Hydrogel	Cervical Cancer (CC)	They have been explored for directed activities in CC therapy. These HGs retort to precise stimuli such as temperature, pH, or enzymes, allowing controlled release of therapeutic agents at the tumor site. PEG-PCL-PEG/cisplatin + MPEG-PCL/paclitaxel, or PDMP, are gel-based dual drug delivery systems that have been proven to cause G1 phase block, boost apoptosis, and decrease toxicity in cervical cancer cells.	28
5.	Nanocomposite Hydrogel	Lung Cancer (LC)	Nanocomposite HGs have been studied for their applications in lung cancer therapy. These HGs are composed of a polymer matrix and NPs, which can enhance drug loading capacity and provide targeted delivery to lung tumors. Abraxane consisting of protein‐based NPs, and albumin‐particle bound paclitaxel, is used in the cure of non-small cell LC.	29
6.	Antibody-conjugated Hydrogel	Pancreatic Cancer (PC)	Antibody-conjugated HGs have been developed for targeted delivery in PC. These HGs are functionalized with specific antibodies that can recognize and fix receptors overexpressed on pancreatic cancer cells.	30
7.	Injectable Hydrogel	Liver Cancer	Injectable HGs have shown promising results in liver cancer treatment. These HGs can be injected into the liver, providing localized delivery of therapeutic agents. They can also be loaded with imaging agents for real-time monitoring of treatment response. Embelin/PECTgel, a thermosensitive injectable hydrogel with embelin injected into it, was created by Peng et al. The cytotoxicity and anticancer efficacy of embelin/PECTgel against liver cancer were examined. The findings revealed that, when compared to free embelin, Embelin/PECTgel continually released the medicines, increasing their toxicity for H22 cells.	31
8.	Thermoresponsive Hydrogel	Gastric Cancer	Thermoresponsive HGs have been investigated for gastric cancer treatment. These HGs can experience phase transition to temperature changes, allowing for localized drug delivery in the stomach. The hydrogel can form a sol state at body temperature, facilitating drug release at the tumor site. To treat the peritoneal propagation of gastric cancer.	32
9.	pH-responsive Hydrogel	Pancreatic Cancer	pH-responsive HGs have been explored for targeted drug delivery in pancreatic cancer treatment. These HGs can undergo pH-dependent changes in swelling or release behavior, allowing for controlled drug release in the acidic tumor microenvironment.	33

Psoriasis Treatment:

A significant portion of the population suffers from Psoriasis which is a chronic, autoimmune, inflammatory skin condition. These symptoms (pain, itching, and rashes) are brought by increased keratinocyte proliferation in the epidermis along with dilated dermal veins, loss of differentiation under the control of an inflammatory infiltrate in the skin strata, and irregular cell growth^34,35.

According to published research, Carbopol HGs with nanosponge incorporated in them improve drug retention in the intended skin region. The hydration method used by HGs helps increase drug administration into the skin ³⁶. Given that the absence of a natural moisturizing element (like water) is a prevalent aspect of psoriatic skin, this property of HGs may offer an extra benefit in treating this condition. Typically, HGs are used to construct a depot formulation from which the medication gradually elutes, keeping its high concentration in the immediate vicinity for a prolonged time.

In preclinical experiments, Kumar et al. showed that the creation of dithranol nanosponge amalgamated hydrogel (DTHNS-HG) was a successful method for the management of psoriasis. The efficiency of the semisolid dosage form for cutaneous distribution was demonstrated by the examination of the produced DTHNS-HG in terms of spreadability, texture analysis, and viscosity experiments³⁷.

Drug Delivery:

Controlled Release Drug Delivery:

Drugs for systemic effects can be delivered via the skin at a prearranged and regulated rate using transdermal drug delivery (TDD) devices in the form of HG membranes. The benefit of this approach is that it prevents the presystemic metabolism effect. By eradicating the devices, drug distribution tends to be stopped immediately upon request. For the well-ordered discharge of a hydroxyl acid present in tamarind fruit pulp extract, a hydrogel patch made of chitosan and starch cross-linked with GA has been developed³⁸.

Rectal Drug Delivery:

The promising site is local and systemic drug delivery. It can serve as a substitute for IV or other injectable drug delivery methods. For rectal delivery, the DS-loaded chitosan microspheres were mixed into HGs encompassing Carbopol 934 and hydroxypropyl methylcellulose (HPMC)³⁹. The release rates from hydrogel are influenced by the viscosity of rectal HGs. According to the results, HG for rectal administration of 5-fluorouracil may be used to treat rectal cancer⁴⁰. Methotrexate (MTX) was put into HGs made of gelatin (Gel) and Poly (Vinyl Alcohol)(PVA) for transport to the colon. These results show that the generated Gel/PVA HGs have the potential to serve as regulated delivery systems for MTX to the colon⁴¹.

Oral Drug Delivery (ODD):

The highly comfortable and convenient route for the delivery is oral. Mostly entire categories of actives are delivered through the oral route. HGs have a great impending to provide site-specific, controlled release of protein, peptide, and chemotherapeutic compounds for both local and systemic treatment applications, stimuli-responsive HGs in particular take advantage of physiological changes throughout the digestive tract⁴². Despite the difficulties associated with oral administration, numerous hydrogel delivery methods have been created to yield the benefit of physiological changes occurring in the GI tract to accomplish controlled drug release. The most popular methods for site-specific delivery take advantage of the pH gradient and/or enzyme localization. The examples of polymers and applications for oral drug administration in several categories of hydrogel systems.

Vaginal Drug Delivery:

For topical vaginal medication delivery of metronidazole, an innovative strategy relying on mucoadhesive super porous hydrogel hybrids (SPHHs) was tested. SPHHs were created using a process called solution polymerization. The tensile strength, mucoadhesion time, and 24-hour drug release of SPHHs have all been satisfactory. The development of pores and linked capillary channels was visible in SEM images. The innovative drug delivery system based on SPHH that was suggested was created effectively, and SPHH-DDS appears to be a potential candidate for topical vaginal delivery of Metronidazole⁴³. The study assesses blends of HPMC/chitosan hydrogel's anti-Candida effectiveness contrary to 8 dissimilar albicans and non-albicans strains. Overall, the findings show that it is feasible to create HPMC/CS mixed HGs for use in the management and deterrence of Candida contaminations following vaginal administration⁴⁴.

Transdermal Drug Delivery:

Due to its special characteristics, the creation of hydrogel-based patches has recently garnered significant attention. The majority of hydrophilic polymers used to create HGs can preserve a significant volume of water, up to 1,000 times their dry weight. The patches' skin compatibility was satisfactory since there was no redness or pustules throughout the five-day application period ⁴⁵. HGs are a good dosage form for topical application due to the significant amount of water they contain, which plays a decisive part in the elasticity and moisturization of the skin⁴⁶.

For long-term transdermal medication delivery, hydrogel patches rely on water-swellable polyacrylates have been established. Over five days, researchers in humans examined two characteristics that are important to the in-vivo performance of hydrogel patches. These were (i) the kinetics of water altercation amongst the patches and the skin, and (ii) the patches' suitability for different skin types. It was discovered that after around 20hours, water interchange trailed a regular fluctuation pattern, peaking once during the day and once during the night. Initially, there was a progressively rising uptake of water from the skin by the patches.

Ophthalmic Drug Delivery:

It has been demonstrated that giving ophthalmic medications to HGs prolongs the time that they are in touch with the cornea, improving ocular bioavailability. Chitosan and b-glycerophosphate (GP) were combined to create an in-situ thermosensitive hydrogel 46. In comparison to an aqueous solution, the hydrogel increased trans-corneal permeability by a factor of seven. It also increased ocular bioavailability, reduced the requirement for repeated administration, and lessened ofloxacin's adverse effects on the eyes. For the ocular administration of timolol maleate, hydrogel made of chitosan and poly(N-isopropyl acrylamide) was created ⁴⁷. Additionally, the hydrogel's drug release was doubled. Genta et al. created bio-adhesive chitosan microspheres for ophthalmic delivery of acyclovir to boost its ocular bioavailability⁴⁸.

Contact Lenses:

These are clear or colored thin films and are commonly used around the world for improved looks, treating various diseases, reducing limitations, correcting refractive problems, and aesthetic purposes⁴⁹.^.Based on elastic behavior, these lenses can be either hard or soft. Several researchers have created hydrogel contact lenses utilizing both natural and synthetic polymers that have been antibiotic-loaded⁵⁰. To create contact lens hydrogel, a mixture of two separate kinds of medications, such as an antibiotic (moxifloxacin hydrochloride) and an anti-inflammatory (diclofenac sodium), were used along with silicone and other natural polymers like hyaluronate, alginate, and poly-lysine. The releasing property of the formulation with non-toxicity, no eye irritation, and decreased cellular adhesion was changed as a result of molecular imprinting^51,52.

One of the most well-known producers of soft contact lenses nowadays is Bausch & Lomb. Bausch & Lomb makes soft contact lenses for short- and long-sightedness under the brand names SofLens Daily disposable, Ultra Contact lens, PureVision2 HD, iconnect, and New Biotrue®⁵³.

Hygiene Products:

Superabsorbent polymers (SAPs) were first used in agriculture and diapers some thirty years ago, and their applications have subsequently expanded to include a variety of other applications due to their remarkable water retention⁵⁴. For usage in feminine napkins, SAPs were initially commercially produced in Japan in 1978, the first SAP material being cross-linked starch-g-polyacrylates⁵⁵^,⁵⁶.

Cosmetic Applications:

Cosmetics are employed to expand the appearance and texture of skin. Some of the cosmetics used to keep the body in good condition include moisturizers, body lotions, and skin cleansers. Because of their biocompatibility, elasticity, softness, and high water content, HGs are currently gaining increased attention from the cosmetics industry⁵⁶.

Skin hydration is critical for maintaining its appearance and texture⁵⁷. Skin problems, such as wrinkles, nasolabial folds, anti-aging, skin augmentation, skin hydration, and collagen stimulation have also been treated with Hyaluronic acid (HA) HGs. Several publications established the auspicious anti-wrinkle potential of HA-based formulations. However, because HA is an expensive biopolymer, it is only occasionally employed in hair treatment cosmetics⁵⁸.

Collagen is a strongly cross-linked substance that is typically soluble neither in water nor in oils. It's better not to use it as a raw material for cosmetic preparation because it's insoluble in water. In the presence of bacteria like Methylobacterium, Solibacter usitatus, and Rhodopseudomonas palustris, collagen can be created through fermentation. In addition to reducing wrinkles, collagen-based HGs are also used to treat acne scars and repair nasolabial folds ⁵⁹⁶⁰^.

Clinical Trials

A wide variety of molecules are presently in clinical trials aimed at dealing with several diseases depicted in Table 4.

Table 4: List of agents in clinical trials

S. No	Type of Hydrogel	NCT Number	Phase	Condition/Disease	Current Status
1.	Silicone hydrogel	NCT03139812	4	Corneal Epithelial Permeability	Completed
2.	Polyacrylamide hydrogel	NCT02550899	4	Anal Incontinence	Completed
3.	Fitostimoline Hydrogel	NCT05661474	4	Diabetic Foot	Completed
4.	Metronidazole Hydrogel	NCT04983849	4	Stage II and Stage III Periodontitis	Completed
5.	Loxoprofen Hydrogel	NCT03800797	4	Ankylosing Spondylitis	Completed
6.	Silicone Hydrogel	NCT01543061	4	Contact Lens Related Dry Eye Syndrome	Completed
7.	Omega-3 Hydrogel	NCT05214495	3	Mucositis Oral	Completed
8.	Polyacrylamide hydrogel	NCT01077765	3	· HIV Infection · Antiretroviral Side Effects · Lipodystrophy Syndrome Related to HIV Infection	Completed
9.	Silicone Hydrogel	NCT00520689	3	· Myopia · Hyperopia	Completed
10.	LSH Silicone Hydrogel	NCT01735045	3	Myopia	Completed
11.	Silicone Hydrogel	NCT00520351	3	Myopia	Completed
12.	RadiaPlexRx Hydrogel	NCT00481884	3	Radiation Dermatitis	Completed
13.	BioSentry Hydrogel	NCT02224924	3	Lung Biopsy	Completed

4. CONCLUSION:

The therapy for several diseases is unsatisfactory when conventional approaches are employed. The precincts associated with the conventional dosage forms are higher dose, poor efficacy, and toxicity. The hydrogel-based drug delivery is gaining tremendous popularity for the therapy of several diseases due to their controlled or targeted action, mechanical strength, biocompatibility, patient comfort, and convenience. In the therapy of cancer, hydrogel-based products are highly beneficial with minimal adverse effects. Moreover, the HGs-based products are highly effective in oral, ophthalmic, transdermal, vaginal, rectal, and cosmetics, etc. Hence, it was concluded that hydrogel is a versatile nanocarrier in the drug delivery system.

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Received on 23.01.2025 Revised on 16.04.2025

Accepted on 07.05.2025 Published on 08.07.2025

Available online from July 12, 2025

Asian J. Pharm. Tech. 2025; 15(3):289-295.

DOI: 10.52711/2231-5713.2025.00044

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Polymer	Description
Polyethylene glycol (PEG)	PEG is a polymer that dissolves in water. Due to its biocompatibility, nontoxicity, and water solubility, PEG is employed in HGs. Because PEG-based HGs are stimuli-based HGs, they are also known as "smart polymers" or "intelligent gels”. These HGs are also utilized for controlled-release drug delivery.
Poly (N isopropylacrylamide) (PNIPAAm)	PNIPAAm HGs demonstrated a lower critical solution temperature (LCST) behavior, making them useful in medical and electrical applications ⁹.
Polyacrylamide (PAAm)	PAAm HGs are extremely BC and cross-linked with numerous cross-linkers to control their properties. They are extensively incorporated in TE and drug delivery applications ⁵
Alginate	Alginate HGs are BC and can be easily cross-linked with divalent cations, such as Ca2+. They are widely used in TE, wound healing (WH), and drug delivery applications ⁷.
Chitosan	Glucosamine and N-acetyl glucosamine units are the building blocks of chitosan. Chitosan is used in pharmaceutical applications such as drug carriers, tablet excipients, gel formers, powder, and emulsions because it is biodegradable, BC, and non-toxic.
Gelatine	Gelatine is made by hydrolyzing collagen extracted from animal connective tissues and bones. Gelatine is employed in gene delivery, cell culture, protein delivery, and WH.
Hyaluronic acid (HA)	HA is a naturally occurring polymer that can be found in the synovial fluid, vitreous of the eye, and tissues of higher animals. Due to its biocompatibility and non-immunogenicity characteristics, it is employed in preparations for the nasal, pulmonary, parenteral, and ophthalmic routes ⁶. Therapeutic agents are delivered using HGs made of HA for tissue regeneration and drug targeting ¹⁰.