1. INTRODUCTION:

Skin diseases affect millions of individuals globally, imposing significant physical, emotional, and financial burdens. Traditional treatments, such as topical creams and oral medications, often face limitations like poor patient compliance, low drug stability, and adverse side effects.

Hydrogels are three-dimensional network structures able to imbibe large amounts of water. Hydrogels do not typically dissolve due to chemical or physical cross-links and/or chain entanglements. They exist naturally in the form of polymer networks such as collagen or gelatin, or can be made synthetically.¹ Environmentally sensitive hydrogels can serve a wide variety of applications because of their ability to respond to environmental changes, typically by exhibiting changes in volume.²

Traditional stimuli that elicit hydrogel response are pH, temperature, and ionic strength. Analytes and biomarkers including glucose, proteins, and DNA also elicit hydrogel responses.² Because of such a wide variety of response triggers, hydrogels can be incorporated into sensors or actuators, or can be utilized in controlled drug delivery systems, biosensors, tissue engineering scaffolds, artificial organs, wound healing bandages, physiological membranes, contact lenses, and microfluidic valves.

Hydrogels are widely used in many different industries because of their high water holding capacity, elastic nature, compatibility with living tissue, and flexibility.³ In the second phase, which started in the 1970s, researchers worked to create a more sophisticated hydrogel that could react precisely to changes in temperature and pH. Biocompatible and adaptable supramolecular inclusion complexes are the building blocks of third-stage hydrogels. “Smart hydrogels” were created as a result of the hydrogels created in the third stage of development. Hydrogels have been employed since the 1980s to include numerous traditional and new formulations for a variety of biomedical disciplines, including contact lenses, absorbent cotton, sutures, and cell engineering, as well as biosensors, drug delivery, cell therapy, and 3D cell culture.

2. Advantages of Hydrogels in Dermatology over Conventional Dosage Forms

Comparing hydrogels to conventional dosage forms as lotions, ointments, or creams reveals clear benefits in dermatological applications. High water content is made possible by their three-dimensional, hydrophilic polymeric network, which creates a moist environment that is necessary for wound healing and skin regeneration.⁴ In contrast to greasy ointments that can irritate the skin or clog pores, hydrogels are breathable, non-greasy, and skin-calming. They have the ability to stick to the application site well without leaving any residue, which improves the penetration of active ingredients and permits regulated, prolonged medication release. Furthermore, while retaining their structural integrity and biocompatibility, hydrogels can integrate a variety of therapeutic substances, including as antibiotics, anti-inflammatory medications, herbal extracts, and nanoparticles.⁵ These characteristics improve patient compliance and therapeutic efficacy, making hydrogels particularly appropriate for burns, ulcers, chronic skin conditions, and post-surgical dressings.

3. Synthesis of Hydrogel:

Hydrophilic monomers, which can be engineered in synthetic methods beforehand to accommodate particular application features, are typically used in the creation of hydrogels. Polymers, either natural or synthetic, can be cross-linked to create hydrogels. Following extensive stages of hydrolysis and polymerization, the polymer chains form a covalent link with a fully 3D network microstructure. By using this technique, the hydrogel’s mechanical strength (fracture energy < 100 J/m−2) may be guaranteed, and it can be kept from dissolving in an aqueous environment.⁶

Various synthesis strategies for hydrogels are summarized below –

3.1 Physical crosslinking synthesis:

Physical hydrogels sometimes referred to as supramolecular or thermoplastic hydrogels are reversible solids that have elasticity and viscosity and are appropriate for room temperature applications. Intermolecular interactions (hydrogen bonding, electrostatic attraction, ionic bonding, polymer entanglement, crystallite formation and van der Waals forces, etc are what give rise to the phrase “physical crosslinking” of the process.⁷

Because no external chemical crosslinking agents are added, physical crosslinking procedures are gentler and easier to prepare than chemical crosslinking procedures. They also have superior biocompatibility and lower toxicity.⁸ In addition, the unstable state of hydrogels made by physical crosslinking raises the possibility of 3D network degradation at high temperatures. This guarantees the physical hydrogel’s degradability and non-polluting characteristics. But because of this particular property, as the environment changes, the hydrogel’s state will likewise alter or perhaps dissolve completely. Thus, it is not suitable for application in some environments which require long-term service.

(a) Hydrogel bonding:

Because of their ability to respond to light, temperature, and pH, hydrogels are widely used in biological tissue engineering. Non-covalent crosslinking employing hydrogen bonds, electrostatic attraction, and their combinations is known as self-assembled crosslinking. They are able to produce hydrogels that are highly elastic and have shear thinning characteristics, making them ideal for 3D bio printing.⁹ It can be immediately administered through a very thin needle or catheter and shield cells from strong shear forces because of its rheological characteristics, stress-relaxation behavior, and low shear viscosity. Consequently, it has found extensive application in scaffolds, embolic biomaterials, and cell transport. Hydrogels cross-linked by hydrogen bonding are still challenging to inject, though, because of their high gel concentration, and their poor crosslinking density results in subpar mechanical strength.

(b) Crystalline formation:

The process of freezing a polymer solution to at least -15 °C, quickly melting it at ambient temperature, and repeating the process until a 3D gel network is generated is known as the “freeze-thaw method,” which is also used to form crystallites. Toxic chemicals are not added at all during this procedure, and the number of freezing cycles and the initial concentration of the polymer solution can be changed to modify the properties of the hydrogel. For instance, several cycles will increase the mechanical strength by causing the gel network to grow closer together.¹⁰

Simultaneously, the mechanical characteristics become stronger with increasing initial polymer solution concentration. This is due to the interaction between the polymer molecular chains in the frozen state. For instance, the polyvinyl alcohol (PVA) chain creates ordered polymer crystals locally after forming hydrogen bonds with hydroxyl groups. Consequently, with a constant increase in PVA strength, opaque hydrogels with the crystal zone acting as physical crosslinking points will emerge during the process of cyclic freezing and thawing.

3.2 Chemical cross-linking synthesis:

Because of their synthetic technique, which involves the production of covalent bonds to bring about mechanical, chemical, and thermal stability, hydrogels produced through chemical crosslinking are also known as thermosetting hydrogels or eternal hydrogels. Crosslinking techniques used in this procedure include photo crosslinking, enzymatic crosslinking, radiation crosslinking, co-/graft-polymerization crosslinking, and others.¹¹ Chemical crosslinking has the benefit of allowing hydrogels to be pre-designed with the characteristics needed for various applications. Additionally, advances in technology have made it possible to create complex material systems with a broad range of uses. The disadvantages are still very clear, though: in biological applications, hazardous chemical crosslinking agents may be harmful to human health.

(a) Radiation crosslinking:

Hydrogels can be made via radiation crosslinking, a comparatively environmentally friendly chemical crosslinking technique, without the need for chemical initiators or cross linkers. Radiation cross-linked hydrogels appear to be safer and more pure, which is why the biological disciplines use them extensively.¹² But its exorbitant cost makes large-scale manufacturing impossible, therefore its application is limited to small-scale laboratory synthesis. High energy sources, such as microwaves, gamma rays, and ultraviolet light, are needed for excitation in the radiation crosslinking process. Water is also required because it provides free radicals, such as e−, H+2O*, H2O, and ·OH, which are essential for the entire process.

Thus, another type of radical polymerization that is included in this category is radiation crosslinking. The breakdown of water molecules and the crosslinking of the polymers occur simultaneously due to the high penetration and wide radiation area of the high-energy electron beam. This causes intermolecular radical recombination, which speeds up the conversion process of the polymer into hydrogel and results in a more uniform gel structure. Furthermore, radiation crosslinking preserves the matrix’s sterilization and biocompatibility while not destroying its native matrix structures.¹³

(b) Crystallite formation:

Another name for photo-cross-linked hydrogels is photocured hydrogels. In the preparation process, the hydrophilic polymer aqueous solution is exposed to UV or visible light to initiate a gel-curing process, which is analogous to radiation crosslinking. Stated differently, this approach facilitates the synthesis of hydrogels in situ while avoiding the use of hazardous chemicals.¹⁴ It can produce transparent hydrogels for cell observation and has strong mechanical properties and quick gelation.

Adjustable and inversely correlated with the precursor concentration is the gelation duration. To date, photo-cross-linked hydrogels have found numerous uses, such as energy storage devices, regenerative scaffolds, medication delivery, etc.

3.3 Enzymatic crosslinking:

The use of injectable (or spray) hydrogels created using in situ enzymatic crosslinking has been extensively utilized in the field of biological tissue engineering. Enzymatic crosslinking has milder reaction conditions and processes, faster gelation speed, and greater controllability when compared to other crosslinking techniques.¹⁵ More significantly, biocompatibility is ensured during the entire process by a harmless chemical catalyst. These days, it’s employed for surgical adhesion prevention or in situ hemostasis. H2O2, transglutaminases, tyrosine, lysyl oxidase, horseradish peroxidase (HRP), and phosphatases are among the substances utilized.

So far, two of the most basic gelation mechanisms have been described. The physical crosslinking mechanism can be attributed to −NH, −OH or −COOH interactions between polymer chains through hydrogen bonding and ion interactions. The mechanism of chemical crosslinking is to stabilize the hydrogel network by forming 3D chemical covalent bonds.¹⁶

4. Properties of Hydrogels in Dermatology:

4.1 Biocompatibility and Biodegradability:

Hydrogels are generally composed of materials that are safe for biological applications, including natural polymers (e.g., collagen, alginate) and synthetic polymers (e.g., polyvinyl alcohol, polyethylene glycol). Their biodegradability ensures minimal environmental impact and avoids long-term residues in the skin.¹⁷

4.2 Moisture Retention:

Hydrogels maintain a moist environment conducive to skin healing, particularly in wound care, by preventing dehydration and promoting cell migration.¹⁸

4.3 Tunable Mechanical Properties:

The elasticity, porosity, and swelling capacity of hydrogels can be adjusted to suit specific therapeutic needs, ranging from soft tissues to more rigid skin structures.¹⁹

Figure 4: Mechanism of action of Hydrogels

7. Challenges in Hydrogel Applications:

Table 2:Challenges and possible solutions for hydrogel applicatons

Challenge	Description	Impact	Possible Solutions
Mechanical Strength and Stability	Natural hydrogels often lack mechanical robustness and structural integrity.	Limits application on movable or stressed skin regions.	Use of crosslinking agents, composite hydrogels, or nanomaterial reinforcement.³²
Limited Drug Loading & Burst Release	Difficulty in loading hydrophobic or large drugs; may release drug too quickly (burst effect).	Reduced therapeutic window and potential toxicity.	Incorporation of nanoparticles or micelles; tuning polymer density.³³
Uncontrolled/Incomplete Degradation	Degradation may be too rapid or leave behind residues.	Alters drug release kinetics; may cause inflammation or toxicity.	Design of biodegradable polymers with tailored degradation profiles.³⁴
Complex Manufacturing & Sterilization	Sensitive synthesis conditions and sterilization challenges.	Impacts scalability and regulatory approval.	Development of standardized, GMP-compliant fabrication processes.³⁵
Storage Instability & Shelf Life	High water content can lead to microbial growth or drying.	Requires special storage; short shelf life.	Use of preservatives or development of dry/reconstitutable hydrogels.³⁶
Poor Skin Penetration/Retention	Limited diffusion of drugs through stratum corneum or into deep skin layers.	Reduced efficacy for deep-seated lesions or tumors.	Integration with microneedles, permeation enhancers, or nanocarriers.³⁷
Regulatory Challenges	Drug-device hybrid classification complicates regulatory approval.	Slows clinical translation and increases development costs.	Early engagement with regulatory bodies; robust preclinical safety and efficacy data.³⁸
Patient Compliance Issues	Some hydrogel dressings may be uncomfortable or require frequent changes.	Lower adherence to treatment protocols.	Develop user-friendly, self-adhering, pain-free, transparent formulations.³⁹

8. Marketed products:

Table 3: Marketed products with drugs and there use

S. No.	Product Name	Drug Name	Indication/Use
1.	Adlarity	Donepezil	Treatment of Alzheimer’s disease
2.	Bisono	Bisoprolol	Treatment of atrial fibrillation
3.	Butrans	Buprenorphine	Management of pain
4.	Catapres-TSS	Clonidine	Treatment of hypertension, tic disorder, Tourette syndrome and ADHD
5.	Daytrana	Methylphenidate	Treatment of ADHD
6.	Duragesic	Fentanyl	Treatment of moderate to severe pain
7.	Exelon	Rivastigmine	Treatment of Alzheimer’s disease
8.	Fematrix	Estrogen	Treatment of postmenstrual syndrome
9.	Neupro	Rotigotine	Treatment of Parkinson’s disease
10.	Ortho Evra	Ethinyl estradiol and Norelgestromin	Prevention of pregnancy
11.	Oxytrol	Oxybutrnin	Treatment of overactive bladder
12.	Sancuso	Granisetron	Prevention of nausea and vomiting caused by chemotherapy
13.	Secuado	Asenapine	Treatment of mania and bipolar disorder
14.	Transder-Scop	Scopolamine	Prevention of motion sickness
15.	Xelstrym	Dextroamphetamine	Treatment of ADHD

9. Future Perspectives:

In order to enhance the therapeutic outcome, numerous efforts have been made in the past few decades to create targeted drug delivery systems that allow the drug to be delivered to particular organs, tissues, cells, or organelles in the body.^41-43 In this regard, self-assembled nanocarriers that actively target overexpressed antigens or receptors in tumor cells are being thoroughly investigated as a crucial therapeutic strategy. Numerous biomedical applications, such as the detection of cell metabolites and pathogens, tissue engineering, wound healing, cancer monitoring, and the identification of low-molecular-weight endogenous ligands like glucose, lactate urea, and cholesterol, have been studied for hydrogel-based biosensors. Biosensors have recently been created using molecular imprinting techniques that combine biological molecules with monomers and cross-linking agents. Nowadays, a lot of attention is being paid to the fabrication of 3D-printed products employing hydrogels. The gaps between the present in vitro tissue engineering models may be filled by integrating nanotechnology and dynamic techniques like 3D printing into the tissue engineering systems. A new method in hydrogel-based bioprinting is being developed to create scaffolds loaded with cells that can produce sophisticated tissue architecture, anatomical size, and tissue-specific functionalities.

Smart Hydrogels:

Incorporating stimuli-responsive materials (e.g., temperature, pH-sensitive hydrogels) can enable on-demand drug release for more efficient treatment.^44-45

Nanotechnology Integration:

Embedding nanoparticles in hydrogels could enhance their antimicrobial, anti-inflammatory, and regenerative properties.^46-47

Personalized Medicine:

Customized hydrogel formulations tailored to individual patients' needs could revolutionize skin disease management.⁴⁸

Sustainability:

Developing eco-friendly hydrogels using renewable resources can address environmental concerns associated with synthetic polymers.⁴⁹

10. CONCLUSION:

Hydrogels offer a versatile and promising approach for the treatment of skin diseases, combining moisture retention, drug delivery, and biocompatibility into a single platform. Despite challenges, advancements in material science and technology are likely to propel hydrogel-based therapies into mainstream dermatological practice, improving patient outcomes and quality of life. Because of their exceptional capacity to deliver regulated medication release, sustain a moist wound environment, and promote skin regeneration, hydrogel-based devices represent a promising new frontier in dermatological care. They are appealing options for both traditional and cutting-edge drug delivery methods due to their adaptability, biocompatibility, and customizability. However, a number of issues need to be seriously addressed in order to convert these advantages into practical practice. Long-term usage may be hampered by problems such formulation stability, microbial contamination susceptibility, and inadequate mechanical strength. Furthermore, possible side effects such delayed degradation, allergic reactions, or skin irritation create safety issues that need careful preclinical research. Significant obstacles are also presented by regulatory barriers, especially for intricate hydrogel systems that are categorized as drug-device combinations and require thorough documentation of efficacy, safety, and quality. Future studies should concentrate on creating next-generation hydrogels with strong clinical validation, such as platforms based on nanocomposite technology, self-healing, or stimuli-responsive hydrogels. Unlocking the full therapeutic potential of hydrogels in skin-related diseases will require addressing these scientific and translational obstacles.

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Received on 29.06.2025 Revised on 22.10.2025

Accepted on 31.01.2026 Published on 15.04.2026

Available online from April 18, 2026

Asian J. Pharm. Res. 2026; 16(2):193-200.

DOI: 10.52711/2231-5691.2026.00029

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

S. No	Skin Infection	Hydrogel	Major Pathogen
1)	Acne	Aza- and TTO- loaded ME hydrogel. Chitosan-based hydrogel with methylene blue.	S. aureus, S. epidermis, P. acne
1)	Impetigo	PF-127-chitosan hydrogel embedded with cephalexin NPs pH-responsive DAP-loaded hydrogel.
2)	Leprosy	pH-responsive DAP-loaded hydrogels.	Mycobacterium leprae, Myobacterium lepromatosis
3)	HSV infection	Optimized ACV nanoemulsion hydrogel Tannic acid modified silver nanoparticle based hydrogel.	HSVI, HSV2
4)	Fungal skin diseases	MN-loaded SLN –bearing hydrogel ITR loaded NSVs	Dermatophyte Candida
5)	Scabies	CRT loaded TTO ME-based hydrogel BB-loaded microemulsion hydrogel.	Sarcoptes scabiei
6)	Molluscum contagiosum	2.5% lidocaine/prilocaine hydrogel	MCV