Formulation And Characterization Biodegradable Nutraceutical-Loaded Hydrogel Patches For Combating Digital Eye Strain: A Comprehensive Review

The human eye is a highly specialized sensory organ with a complex anatomical and physiological organization that enables visual perception and maintenance of ocular homeostasis. Anatomically, the eye can be broadly divided into anterior and posterior segments. The anterior segment comprises the cornea, conjunctiva, aqueous humour, iris, ciliary body, and crystalline lens, whereas the posterior segment includes the sclera, choroid, retina, and retinal pigment epithelium [1]. The ocular surface, particularly the cornea and conjunctiva, represents the primary interface between the eye and the external environment and is continuously exposed to environmental, mechanical, and digital-device-associated stressors.

Rapid technological advancement during the digital era has transformed communication, education, professional activities, entertainment, and access to information. Computers, smartphones, tablets, laptops, e-readers, and other digital display devices have consequently become integral components of everyday life. Although these technologies provide substantial social, educational, and occupational benefits, prolonged and continuous screen exposure has simultaneously generated concerns regarding ocular and visual health. Digital eye strain (DES), also referred to as computer vision syndrome (CVS), is among the most frequently reported consequences of prolonged digital-device use [2].

Digital eye strain is characterized by a collection of recurrent ocular and visual symptoms that develop or worsen during or after digital-screen use. The Tear Film & Ocular Surface Society has described DES in terms of the appearance or exacerbation of ocular symptoms and signs associated with digital-device use. CVS is a closely related terminology that has traditionally been used to describe visual and ocular complaints associated with sustained computer and screen-based activities and has increasingly been recognized as an occupational and public health concern [3,4]. The widespread integration of digital devices into education and professional environments has further increased daily screen exposure, particularly among students, office workers, healthcare professionals, and individuals engaged in technology-intensive occupations [5,6]. The clinical manifestations of DES are diverse and may include ocular dryness, burning, irritation, foreign-body sensation, blurred or fluctuating vision, ocular fatigue, difficulty maintaining near focus, and headache. Prolonged screen use may also be accompanied by extra-ocular symptoms such as neck, shoulder, and back discomfort and generalized fatigue, contributing to the overall functional burden of the condition [5,7]. Continuous screen viewing for periods of approximately two hours has been reported to be sufficient to induce or aggravate symptoms in susceptible individuals [1,8]. However, symptom severity is influenced by several factors, including duration and frequency of screen exposure, viewing distance, font size, ambient illumination, screen characteristics, posture, blink behavior, refractive status, and pre-existing ocular-surface abnormalities.

1.1 Ocular Surface and Tear-Film Homeostasis

The ocular surface is a dynamic functional unit comprising the cornea, conjunctiva, lacrimal glands, meibomian glands, eyelids, and nasolacrimal drainage system. These structures interact through coordinated neural, vascular, immune, endocrine, and epithelial mechanisms to preserve ocular integrity and visual performance [12]. As the principal interface between the eye and the surrounding environment, the ocular surface provides mechanical, chemical, antimicrobial, and immunological protection while maintaining a smooth and hydrated optical surface.

The tear film plays a central role in maintaining ocular-surface homeostasis. It provides lubrication, facilitates nutrient and oxygen exchange, contributes to antimicrobial defense, and maintains a smooth refractive surface essential for high-quality vision. The aqueous component is primarily supplied by the lacrimal glands and contains water, electrolytes, proteins, enzymes, and other protective factors. Corneal and conjunctival epithelial cells contribute mucins that facilitate tear spreading and interaction with the ocular surface, whereas the meibomian glands produce a lipid-rich layer that reduces excessive tear evaporation and contributes to tear-film stability [13]. Prolonged digital-device use can disturb this finely regulated system. Concentrated visual attention during screen viewing is frequently accompanied by a reduction in spontaneous blink rate and incomplete blinking. These changes may increase tear evaporation and compromise tear-film stability. Disturbances in tear-film homeostasis can subsequently contribute to increased tear osmolarity, ocular-surface irritation, epithelial stress, and inflammatory signaling [13]. Therefore, tear-film instability and ocular-surface dysfunction represent important physiological components of the pathophysiology of DES.

1.2 Digital Eye Strain and Ocular-Surface Dysfunction

DES is a multifactorial condition rather than a single structural ocular disease. Its manifestations may arise from the interaction of ocular-surface stress, accommodative and binocular visual demands, environmental conditions, and individual susceptibility. Reduced blinking and prolonged visual fixation can increase evaporative stress on the tear film, whereas sustained accommodation and convergence during near-screen activities may contribute to visual fatigue and difficulty refocusing [15]. Several pre-existing conditions may further increase susceptibility to DES, including dry-eye disease, uncorrected refractive errors, binocular-vision abnormalities, contact-lens use, and inappropriate visual ergonomics [15]. Environmental factors such as low humidity, air-conditioning, airflow directed toward the face, inadequate illumination, and screen glare may further aggravate ocular discomfort. Consequently, effective management of DES requires consideration of both symptomatic ocular-surface support and the underlying environmental and behavioral factors contributing to screen-related discomfort.

Figure 1: Oxidative Stress and Eye Diseases

Figure 2: Core Molecular Pathways of Digital Eye Strain (DES)

3.3.1 Marigold (Tagetes erecta) – Lutein and Zeaxanthin

Marigold (Tagetes erecta L.) is an important botanical source of the xanthophyll carotenoids lutein and zeaxanthin and is widely utilized for the production of carotenoid-rich nutritional ingredients. Marigold extracts contain predominantly lutein, together with smaller quantities of zeaxanthin and their corresponding esters. Following absorption, these xanthophyll carotenoids are selectively distributed within ocular tissues, particularly the macular region, where they contribute to optical filtering of short-wavelength visible light and provide antioxidant protection against photooxidative stress [63,64].

Lutein and zeaxanthin are of particular interest in the context of prolonged digital-device use because oxidative stress and visually demanding near work may contribute to visual fatigue and ocular discomfort. Their ability to absorb portions of the blue-light spectrum and neutralize reactive oxygen species provides a mechanistic rationale for their investigation as supportive nutritional agents for screen-associated visual stress. A randomized controlled study conducted in individuals with frequent electronic-screen exposure reported that six months of lutein and zeaxanthin supplementation was associated with improvements in selected ophthalmic parameters, including Schirmer test results, photostress recovery, and tear-film breakup time, although not all subjective outcomes differed significantly from placebo [65]. These findings suggest potential benefits of lutein and zeaxanthin for ocular function in individuals with high screen exposure; however, evidence from oral supplementation cannot be directly extrapolated to a topical hydrogel patch.

Marigold-derived lutein and zeaxanthin are therefore attractive candidates for incorporation into nutraceutical delivery systems because of their antioxidant and photoprotective characteristics. Nevertheless, both compounds are highly lipophilic and exhibit poor aqueous solubility. Their incorporation into a hydrophilic hydrogel therefore presents formulation challenges related to solubilization, dispersion, chemical stability, protection against oxidation, and uniform distribution within the polymeric matrix [64,66]. Appropriate approaches such as lipid-based carriers, emulsification, cyclodextrin complexation, nanoencapsulation, or incorporation of suitable solubilizing excipients may be considered to improve their formulation performance.

3.3.2 Bilberry (Vaccinium myrtillus) – Anthocyanins

Bilberry (Vaccinium myrtillus L.) is a recognized botanical source of anthocyanins, including delphinidin-, cyanidin-, malvidin-, petunidin-, and peonidin-derived glycosides. These polyphenolic pigments possess pronounced antioxidant activity and have been investigated for their potential effects on vascular, retinal, and ocular-surface function [67]. Their ability to scavenge reactive oxygen species and modulate oxidative and inflammatory signaling makes bilberry anthocyanins relevant to nutraceutical approaches targeting ocular stress. The potential relevance of bilberry to DES is supported indirectly by evidence obtained from ocular-surface and dry-eye research. A randomized, double-blind, placebo-controlled study of standardized bilberry extract in individuals with dry-eye symptoms reported improvement in tear secretion and systemic antioxidant status following oral supplementation [68]. Since ocular dryness and discomfort constitute important components of DES, such findings provide a rationale for further investigation of bilberry-derived anthocyanins in screen-associated ocular stress.

However, the available evidence predominantly concerns oral administration, and the pharmacokinetic behavior of anthocyanins following topical or periocular application may differ substantially. Furthermore, anthocyanins may be susceptible to degradation depending on pH, temperature, oxygen exposure, light, and formulation environment. Consequently, incorporation into a hydrogel system would require careful optimization of polymer composition, pH, antioxidant protection, packaging, and storage conditions [67,69]. These considerations make bilberry anthocyanins promising but formulation-sensitive candidates for biodegradable nutraceutical hydrogel patches.

3.3.3 Saffron (Crocus sativus) – Crocin and Crocetin

Saffron (Crocus sativus L.) contains several biologically active constituents, among which crocin and crocetin are particularly relevant to ocular-health research. These carotenoid-derived compounds have demonstrated antioxidant, anti-inflammatory, neuroprotective, and cytoprotective properties in experimental studies [70]. Saffron-derived bioactives have been investigated in relation to retinal function and disorders involving oxidative and neurodegenerative mechanisms, including age-related macular degeneration and other retinal conditions [71]. The potential relevance of crocin and crocetin to DES is primarily related to their ability to modulate oxidative stress and inflammatory pathways. Because prolonged visual activity and screen-associated environmental stress may increase oxidative burden, compounds capable of enhancing cellular resistance to oxidative injury may provide supportive benefits. Clinical and experimental studies involving saffron supplementation have reported effects on visual function and retinal parameters, although these findings primarily concern retinal disorders rather than DES itself [70,71]. Accordingly, saffron-derived bioactives should presently be regarded as potential nutraceutical candidates rather than established treatments for digital eye strain. Their incorporation into a biodegradable hydrogel patch may be explored to provide localized delivery of antioxidant compounds; however, appropriate studies are required to establish their stability, loading capacity, release behavior, permeation, safety, and biological activity following topical application.

3.3.4 Turmeric (Curcuma longa) – Curcumin

Curcumin is the principal biologically active polyphenolic constituent of turmeric (Curcuma longa L.). It has been extensively investigated because of its antioxidant, anti-inflammatory, antimicrobial, and cytoprotective activities. Curcumin can interact with several molecular pathways associated with oxidative stress and inflammation, including NF-κB, MAPK, and Nrf2-associated signaling. These characteristics have generated considerable interest in its application to ocular disorders involving oxidative injury and inflammation, including experimental dry-eye and ocular-surface conditions [72,73]. From a DES perspective, curcumin is of interest because oxidative stress and inflammatory signaling have been proposed as components of the biological response associated with prolonged digital-device use. Its antioxidant activity may help neutralize reactive oxygen species, while its anti-inflammatory effects may potentially modulate inflammatory signaling associated with ocular-surface stress. However, direct clinical evidence demonstrating that curcumin specifically prevents or treats DES remains limited, and its potential role should therefore be considered supportive and investigational. A major limitation of curcumin is its extremely low aqueous solubility, chemical instability under certain environmental conditions, and limited bioavailability. These characteristics can restrict its effective utilization in conventional formulations [73,74]. Consequently, advanced delivery systems, including nanoparticles, liposomes, nanoemulsions, polymeric carriers, and hydrogel-based systems, have been investigated to improve its solubility, stability, retention, and controlled release. Incorporation of curcumin into a biodegradable hydrogel could therefore provide an opportunity to overcome some of these limitations while maintaining prolonged contact with the intended application site [74].

3.3.5 Green Tea (Camellia sinensis) – Catechins

Green tea (Camellia sinensis L.) is a rich source of polyphenolic catechins, including epigallocatechin gallate (EGCG), epigallocatechin, epicatechin gallate, and epicatechin. Among these constituents, EGCG has received particular attention because of its potent antioxidant and anti-inflammatory properties. Green-tea catechins can scavenge reactive oxygen species and influence several cellular signaling pathways involved in oxidative stress, inflammation, apoptosis, and cellular protection [75]. The potential relevance of green-tea catechins to DES is associated with the proposed contribution of oxidative stress and inflammatory responses to screen-related ocular discomfort. Experimental ocular research suggests that catechins may exert protective effects against oxidative and inflammatory injury in ocular tissues [75,76]. These properties make green-tea-derived bioactives potential candidates for incorporation into nutraceutical delivery systems designed to support ocular or periocular health. However, direct evidence demonstrating the effectiveness of green-tea catechins in DES, particularly following topical hydrogel administration, remains limited. In addition, catechins can undergo oxidation and degradation during processing and storage, which may influence formulation stability and biological activity. Therefore, hydrogel formulation should consider pH, oxygen exposure, light protection, polymer–polyphenol interactions, and appropriate packaging [76]. Further experimental studies are necessary to determine whether localized delivery of catechins can provide meaningful benefits for digital-screen-associated ocular symptoms.

3.3.6 Grape (Vitis vinifera) – Anthocyanins and Polyphenols

Grape (Vitis vinifera L.) represents an important dietary source of polyphenolic compounds, including anthocyanins, flavonoids, proanthocyanidins, and other phenolic constituents. These compounds exhibit antioxidant and anti-inflammatory properties and have been investigated for their potential role in maintaining ocular and vascular health [77]. Grape-derived polyphenols may neutralize reactive oxygen species and modulate cellular pathways involved in oxidative stress and inflammation. The potential application of grape-derived bioactives to DES is supported primarily by their relevance to ocular-surface oxidative stress and dry-eye-related symptoms. A randomized, double-blind, placebo-controlled study investigating an anthocyanin oligomer preparation derived from grape skin reported beneficial effects in individuals with dry-eye disease [78]. Because ocular dryness, irritation, and discomfort are major components of DES, these findings provide a rationale for further investigation of grape-derived anthocyanins and polyphenols in screen-associated ocular stress.

Nevertheless, the available clinical evidence predominantly involves oral supplementation rather than localized delivery. Consequently, the efficacy and safety of grape-derived bioactives cannot be assumed to be equivalent following incorporation into a periocular hydrogel patch. In addition, the chemical stability of anthocyanins and polyphenols can be influenced by pH, temperature, oxygen, light, and interactions with other formulation components. Therefore, formulation-specific investigations are required to determine loading efficiency, stability, release characteristics, skin compatibility, and biological activity following hydrogel incorporation [77–79]. Overall, the herbal nutraceuticals discussed above represent chemically diverse candidates with complementary mechanisms potentially relevant to DES. Lutein and zeaxanthin provide carotenoid-based photoprotective and antioxidant activity; bilberry anthocyanins offer potent polyphenolic antioxidant activity; crocin and crocetin provide antioxidant and potential retinal-supportive effects; curcumin combines antioxidant and anti-inflammatory activity; green-tea catechins provide polyphenolic redox and inflammatory modulation; and grape-derived anthocyanins and polyphenols offer additional antioxidant and ocular-surface-supportive potential. Their different physicochemical characteristics, however, necessitate individualized formulation strategies when incorporated into biodegradable hydrogel matrices.

4.1 Methods of Formulation of Biodegradable Hydrogel Eye Patches

The selection of an appropriate formulation method for biodegradable nutraceutical-loaded hydrogel patches depends on several factors, including the chemical nature and stability of the nutraceutical, polymer characteristics, desired mechanical properties, degree of biodegradability, intended site of application, swelling behavior, required release profile, and sensitivity of the active constituent to heat, light, oxygen, solvents, and crosslinking conditions. The method must also provide adequate uniformity, reproducibility, structural integrity, and compatibility with the intended route of administration. Commonly investigated approaches for hydrogel-based ocular and periocular delivery systems include solvent casting, freeze–thaw physical crosslinking, ionic gelation, chemical crosslinking, photopolymerization, and advanced additive-manufacturing techniques such as three-dimensional (3D) printing [80–84].

4.1.1 Solvent-Casting Method

Solvent casting is one of the simplest and most widely applicable techniques for preparing thin polymeric films, membranes, and patch-like hydrogel systems. In this approach, the selected biodegradable or biocompatible polymer is dissolved or uniformly dispersed in an appropriate solvent or aqueous medium. The nutraceutical is subsequently incorporated under controlled stirring or homogenization to obtain a uniform formulation. Depending on the intended mechanical characteristics, plasticizers, secondary polymers, humectants, or other functional excipients may be incorporated. The resulting homogeneous dispersion is transferred onto a suitable mould or flat casting surface and subjected to controlled drying to remove the solvent and form a thin polymeric film. The dried film can subsequently be peeled from the casting surface and cut into patches of predetermined dimensions [81,82].

For nutraceutical-loaded systems, solvent casting offers several advantages, including relatively simple processing, low equipment requirements, flexibility in controlling polymer concentration, and the possibility of incorporating thermolabile bioactive compounds under mild processing conditions. Film thickness, polymer concentration, plasticizer concentration, drying conditions, and casting volume can be adjusted to modify flexibility, swelling, mechanical strength, and release characteristics [81,83]. The method is therefore particularly attractive for preliminary development of biodegradable periocular hydrogel patches. However, several formulation challenges must be considered. Inadequate mixing may produce nonuniform nutraceutical distribution, whereas inappropriate drying conditions may result in shrinkage, cracking, excessive brittleness, or residual solvent. Poorly soluble nutraceuticals may undergo precipitation or crystallization during solvent evaporation, leading to dose nonuniformity and altered release behavior. In addition, volatile or oxidation-sensitive phytochemicals may be lost or degraded during processing. For a formulation intended for application around the eye, the selection of solvents and excipients must therefore prioritize biocompatibility, and residual solvent levels should be appropriately controlled [80,82,84].

4.1.2 Freeze–Thaw Crosslinking

Freeze–thaw processing is a physical crosslinking technique particularly associated with poly (vinyl alcohol) (PVA)-based hydrogel systems. During the freezing stage, water molecules form ice crystals and the polymer chains become concentrated within the unfrozen regions. Subsequent thawing promotes formation of crystalline domains and intermolecular interactions that act as physical crosslinking points within the polymer network. Repeated freeze–thaw cycles generally increase the extent of network formation and can modify the mechanical strength, swelling characteristics, porosity, and diffusion-controlled release properties of the resulting hydrogel [82,85].

An important advantage of freeze–thaw crosslinking is that it can reduce or eliminate the need for potentially cytotoxic chemical crosslinking agents. This feature is particularly attractive for systems intended for prolonged contact with sensitive biological tissues. The number and duration of freeze–thaw cycles, polymer concentration, molecular weight, freezing temperature, and thawing conditions can be optimized to control the structural characteristics of the hydrogel [85,86]. For nutraceutical-loaded systems, however, the stability of the active compound must be considered carefully. Repeated exposure to low temperatures and subsequent thawing may influence the physical state, aggregation, oxidation, or activity of sensitive bioactive compounds. Accordingly, the nutraceutical may be incorporated before network formation or loaded after formation of the polymeric matrix, depending on its physicochemical stability and desired release characteristics [82,86]. Freeze–thaw processing may therefore be particularly useful for developing physically crosslinked PVA-containing biodegradable or bioresorbable composite hydrogel systems, provided that the overall polymer composition satisfies the intended safety and degradation requirements.

4.1.3 Ionic Gelation

Ionic gelation is a mild crosslinking approach that utilizes electrostatic interactions between oppositely charged polymers or between polymers and multivalent ions. The method is particularly useful for natural polymers such as alginate and chitosan. Alginate, an anionic polysaccharide, can undergo ionic crosslinking in the presence of divalent cations such as calcium ions, producing an interconnected three-dimensional network. Conversely, positively charged chitosan can interact electrostatically with negatively charged crosslinking agents such as sodium tripolyphosphate (TPP) or with anionic polymers including alginate and hyaluronic acid [80,87]. The mild aqueous processing conditions associated with ionic gelation are advantageous for incorporating thermolabile and oxidation-sensitive nutraceuticals. Because extensive organic solvents and high temperatures can often be avoided, the technique is potentially suitable for incorporating plant-derived compounds such as anthocyanins, flavonoids, polyphenols, and other sensitive bioactives [80,87]. Chitosan–alginate and chitosan–hyaluronic acid combinations may also provide opportunities to modify mucoadhesion, hydration, swelling, and release properties.

For biodegradable nutraceutical-loaded hydrogel patches, the concentration of polymer and ionic crosslinker must be carefully optimized. Excessive crosslinking can produce a dense network with reduced swelling and slower nutraceutical diffusion, whereas insufficient crosslinking may result in inadequate mechanical strength, excessive swelling, and rapid erosion [87,88]. The ionic environment may also influence the stability and ionization state of incorporated nutraceuticals. Consequently, optimization of polymer ratio, crosslinker concentration, crosslinking time, pH, and ionic strength is essential.

4.1.4 Chemical Crosslinking

Chemical crosslinking involves the formation of covalent bonds between polymer chains, producing a relatively stable three-dimensional hydrogel network. Depending on the polymeric components, several chemical strategies can be employed, including aldehyde-mediated crosslinking, carbodiimide-mediated coupling, click reactions, Michael addition, and other covalent crosslinking approaches [84,89]. Chemical crosslinking can provide greater structural stability and allows precise modification of network density, swelling behaviour, degradation rate, and release kinetics. Photo cross linkable polymers such as gelatin methacrylate (GelMA) represent another important class of chemically crosslinked hydrogel materials. GelMA contains methacrylated functional groups that can undergo polymerization in the presence of an appropriate photoinitiator following exposure to light. Such systems have attracted interest for biomedical applications because their network properties can be adjusted by controlling polymer concentration, degree of functionalization, photoinitiator concentration, and irradiation conditions [89,90].

Despite these advantages, chemical crosslinking requires particular attention in ocular and periocular applications. Unreacted monomers, crosslinking agents, photoinitiators, reaction by-products, or residual solvents may potentially produce irritation, cytotoxicity, or inflammatory responses. Therefore, appropriate purification, washing, residual-material analysis, physicochemical characterization, and biological safety evaluation are necessary before considering a chemically crosslinked hydrogel for ocular-related application [84,89]. For nutraceutical-loaded systems, the chemical compatibility of the active constituent with the crosslinking chemistry must also be established because reactive functional groups or processing conditions may alter the stability or biological activity of sensitive phytochemicals.

4.1.5 Photopolymerization

Photopolymerization enables rapid formation of hydrogel networks through light-induced polymerization of photocrosslinkable functional groups. In a typical approach, a photocrosslinkable polymer is combined with a suitable photoinitiator and exposed to a controlled wavelength and intensity of light. The resulting polymerization generates a three-dimensional hydrogel network, and the degree of crosslinking can be regulated through polymer concentration, exposure time, light intensity, and photoinitiator concentration [89,90]. An important advantage of photopolymerization is the ability to produce hydrogel structures with defined geometry and relatively precise spatial control. This characteristic is valuable for customized ocular inserts, microstructured systems, and other geometrically controlled delivery platforms. Photopolymerization may also allow rapid fabrication with minimal mechanical manipulation of the formulation [90]. Nevertheless, the method requires careful evaluation for nutraceutical delivery. Exposure to ultraviolet or high-energy visible radiation may degrade photosensitive compounds, while some photoinitiators and unreacted components may raise concerns regarding biological compatibility. Therefore, visible-light-compatible photoinitiators, optimized irradiation conditions, and appropriate purification strategies may be required. The final formulation must also be evaluated for residual photoinitiator, cytotoxicity, degradation behavior, and active-ingredient stability [89,90].

4.1.6 3D Printing/Advanced Fabrication

Three-dimensional printing represents an advanced fabrication approach capable of producing hydrogel-based structures with precise control over geometry, thickness, internal architecture, porosity, and spatial distribution of formulation components. In extrusion-based bioprinting and related approaches, a polymeric hydrogel or bioink is deposited layer-by-layer according to a predefined digital design. Crosslinking may occur simultaneously or after printing through ionic, chemical, enzymatic, or photochemical mechanisms [90–92]. For ocular drug-delivery applications, 3D printing offers the possibility of producing customized inserts and patient-specific structures with controlled dimensions and potentially tailored release characteristics. The technique may also permit incorporation of multiple materials or active ingredients within different regions of the same structure. Recent investigations into 3D-printed biodegradable ocular and conjunctival delivery systems demonstrate the growing potential of additive manufacturing for personalized ocular drug delivery [90,93]. However, successful 3D printing requires careful control of formulation rheology, viscosity, shear response, extrusion pressure, printing temperature, layer adhesion, crosslinking kinetics, and structural fidelity. These requirements become particularly important when incorporating nutraceuticals because many plant-derived compounds are sensitive to temperature, oxidation, light, and mechanical processing. The printing process must therefore be selected to preserve the chemical integrity and biological activity of the active compound [91,93].

4.2 Evaluation Parameters for the Developed Hydrogel Patch

Following formulation, the patch should undergo systematic evaluation. Important physicochemical tests include appearance, thickness, weight variation, surface pH where applicable, moisture content, swelling index, gel fraction, mechanical strength, tensile properties, folding endurance, and morphology. For nutraceutical-loaded systems, drug/nutraceutical content, entrapment efficiency, content uniformity, chemical stability, and antioxidant activity should also be determined. [94] In-vitro release studies should be conducted using a suitable release medium, with sampling at predetermined intervals. Mathematical models such as zero-order, first-order, Higuchi, and Korsmeyer–Peppas models can be used to investigate the release mechanism. The model should be selected according to the formulation and data characteristics rather than merely choosing the model with the highest correlation coefficient. [74,84] For an ocular formulation, additional studies should include sterility, microbial limits, cytotoxicity, ocular irritation, hemocompatibility where relevant, mucoadhesion, corneal/conjunctival compatibility, and ex-vivo permeation. If the formulation is designed as an external periocular patch, skin irritation, sensitization, transepidermal water loss, skin permeation, and local tolerability become important evaluation parameters. [75,84,90]

CONCLUSION

Digital eye strain (DES) is a multifactorial condition associated with prolonged digital-device use and characterized by dryness, irritation, visual fatigue, blurred vision, headache, and related discomfort. Reduced blinking, tear-film instability, prolonged near fixation, oxidative stress, mitochondrial dysfunction, and inflammatory pathways may collectively contribute to its development. Nutraceuticals such as lutein, zeaxanthin, bilberry anthocyanins, crocin, crocetin, curcumin, green-tea catechins, and grape polyphenols show potential because of their antioxidant, anti-inflammatory, and photoprotective properties. However, most available evidence is based on oral supplementation or experimental ocular models, and their effectiveness when delivered through hydrogel patches remains to be established. Biodegradable hydrogels offer a promising platform for localized delivery because of their hydration, flexibility, biocompatibility, swelling, and controlled-release properties. Nevertheless, formulation development must address nutraceutical stability, loading efficiency, mechanical strength, degradation, release behaviour, irritation, and safety. Overall, nutraceutical-loaded biodegradable hydrogel patches represent a promising research-stage approach for supporting ocular comfort in DES, but comprehensive in-vitro, ex-vivo, in-vivo, and clinical studies are required to establish their safety, efficacy, and therapeutic potential.

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