Research paper on development and evaluation of hydrocortisone nanosponges loaded hydrogel for the topical treatment of psoriasis

Psoriasis

Psoriasis is a chronic, immune-mediated inflammatory skin disorder characterized by accelerated epidermal turnover, resulting in the formation of distinct erythematous plaques covered with silvery scales [1, 2]. This condition affects approximately 2-5% of the global population, with prevalence varying across geographical regions and ethnicities [3, 4]. The disease manifests in several clinical forms, with psoriasis vulgaris (chronic plaque psoriasis) being the most prevalent, accounting for nearly 90% of cases [5]. Other variants include guttate psoriasis, inverse psoriasis, pustular psoriasis, and erythrodermic psoriasis, the latter representing a medical emergency requiring immediate intervention [5, 6].

The pathophysiology of psoriasis involves a complex interplay between genetic predisposition and environmental triggers. Genome-wide association studies have identified susceptibility loci, including the HLA-Cw6 gene and psoriasis susceptibility 1 (PSORS1) gene, which significantly increase disease risk [7, 8]. Environmental factors such as stress, infections (particularly streptococcal upper respiratory infections), trauma (Koebner phenomenon), medications (lithium, beta-blockers, antimalarials), and lifestyle factors including smoking and alcohol consumption can precipitate or exacerbate the condition [8, 9].

At the molecular level, psoriasis is driven by dysregulation of the immune system, particularly involving T-helper 17 (Th17), Th22, and Th1 cell subsets [10]. These activated T cells infiltrate the dermis and epidermis, releasing pro-inflammatory cytokines including interleukin (IL)-17, IL-22, IL-23, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) [10, 11]. This cytokine cascade activates keratinocytes, promoting their hyperproliferation and abnormal differentiation. While normal keratinocyte maturation and shedding occur over approximately 30 days, in psoriatic skin this process is accelerated to merely 6-8 days [3, 12]. The rapidly proliferating keratinocytes accumulate without adequate desquamation, forming the characteristic plaques and scales observed clinically [3, 12].

The disease burden extends beyond physical manifestations, significantly impairing patients' quality of life through psychosocial distress, stigmatization, and association with multiple comorbidities [4, 13]. These comorbidities include psoriatic arthritis affecting up to 30% of patients, cardiovascular disease, metabolic syndrome, obesity, depression, and inflammatory bowel disease [8, 13].

Nanosponge-Loaded Hydrogels: A Synergistic Approach

The integration of nanosponges within hydrogel matrices represents an innovative convergence of two advanced drug delivery technologies, creating composite systems with synergistic advantages [23, 32, 33]. Nanosponge-loaded hydrogels combine the high drug loading capacity, controlled release, and skin reservoir formation of nanosponges with the excellent spreading properties, patient compliance, and moisturizing effects of hydrogels [23, 32, 33].

From a formulation perspective, this approach addresses limitations inherent to each individual system. Nanosponges alone, while excellent drug carriers, may exhibit poor retention on the skin surface and require incorporation into a suitable vehicle for practical application [23]. Conversely, hydrogels alone demonstrate limited capacity for hydrophobic drug encapsulation and uncontrolled drug release kinetics for many therapeutic agents [3, 33]. The composite system overcomes these drawbacks: nanosponges provide efficient encapsulation and sustained release of hydrophobic drugs like hydrocortisone, while the hydrogel matrix ensures uniform application, prolonged skin contact, and enhanced patient acceptability [23, 33].

The drug release mechanism from nanosponge-loaded hydrogels involves multiple kinetic processes: diffusion of drug from nanosponge nanocavities, partitioning between nanosponge and hydrogel phases, and subsequent diffusion through the hydrogel matrix to the skin surface [23, 32]. This complex release profile typically follows sustained kinetics, reducing application frequency and minimizing peak concentration-related side effects [23, 33].

Recent investigations have demonstrated the efficacy of this approach for various therapeutic agents in dermatological disorders. Kumar and colleagues developed clobetasol propionate-loaded cyclodextrin nanosponge hydrogel for psoriasis treatment, reporting significantly enhanced drug solubility (45-fold increase), controlled in-vitro release (86.25% over 24 hours), and superior in -vivo antipsoriatic activity in the mouse tail model compared to conventional hydrogel [41]. The nanosponge formulation demonstrated remarkable increase in orthokeratosis degree and reduction in epidermal thickness, with improved biochemical parameters including oxidative stress biomarkers [41]. Similarly, studies on nanosponge hydrogels containing anti-inflammatory agents have confirmed improved therapeutic outcomes with reduced local and systemic toxicity [32, 33].

 AIM AND OBJECTIVES

The present work entitles “Development and Evaluation of Hydrocortisone Nanosponges Loaded Hydrogel for the Topical Treatment of Psoriasis”

Aim

The primary aim of this research is to develop and evaluate hydrocortisone-loaded nanosponges incorporated into a hydrogel system as a novel topical drug delivery approach for the effective treatment of psoriasis. The study focuses on enhancing drug retention, controlled release, skin permeation, stability, and therapeutic efficacy of hydrocortisone through nanosponge-based hydrogel formulation, thereby improving patient compliance and minimizing adverse effects associated with conventional topical therapies.

Objectives

• To enhance the topical delivery and therapeutic efficacy of hydrocortisone by encapsulating the drug into nanosponge carriers.
• To formulate hydrocortisone-loaded nanosponges using suitable polymers and stabilizers for sustained and controlled drug release.
• To incorporate the optimized hydrocortisone nanosponges into a suitable hydrogel base for effective topical application in psoriasis management.
• To use suitable polymers (e.g., ethyl cellulose, polyvinyl alcohol, carbopol) for the preparation of stable and porous nanosponge structures compatible with hydrocortisone.

Drug and Excipients profile

Drug Profile

Hydrocortisone is a corticosteroid widely used in the management of inflammatory and autoimmune skin disorders such as psoriasis, eczema, dermatitis, and allergic skin conditions. It exerts anti-inflammatory, antipruritic, and vasoconstrictive effects by inhibiting the release of inflammatory mediators including prostaglandins and leukotrienes. Hydrocortisone suppresses the migration of polymorphonuclear leukocytes and reverses capillary permeability, thereby reducing erythema, edema, and itching associated with psoriatic lesions [65-67].

Despite its therapeutic effectiveness, the conventional topical administration of hydrocortisone is associated with limitations such as poor skin penetration, rapid drug removal from the skin surface, low retention time, and systemic side effects upon prolonged use. The hyperkeratotic nature of psoriatic skin further reduces drug permeation [68].

To overcome these limitations, hydrocortisone was formulated into nanosponges. Nanosponges are porous polymeric nanocarriers capable of entrapping drugs and providing controlled drug release with enhanced skin penetration and retention [67].

Hydrocortisone (API)

Surface Morphology

Surface morphology of nanosponges was studied using Scanning Electron Microscopy (SEM) [80,90].

Zeta Potential

Zeta potential was determined using zeta sizer to evaluate stability of nanosponge dispersion [88,91,92].

Entrapment Efficiency

Entrapment efficiency was determined by dissolving nanosponges in methanol and analyzing drug content [80,86].

Entrapment Efficiency (%)=Actual drug contentTheoretical drug content×100

 

 

Production Yield [80,85]

Production Yield (%)=Practical mass of nanospongesTheoretical mass of drug + polymer×100

 

 

 

pH Determination

The pH of hydrogel was determined using digital pH meter [79].

Viscosity

Viscosity of hydrogel formulation was measured using Brookfield viscometer [93].

Spreadability

Spreadability was determined by measuring spreading diameter between two glass slides [94].

Drug Content

Drug content was analyzed by dissolving hydrogel in suitable solvent followed by UV or HPLC analysis [78,79].

In-Vitro Drug Release Study

Drug release study was carried out using Franz diffusion cell with phosphate buffer pH 7.4 as receptor medium.

Samples were withdrawn at predetermined intervals and analyzed spectrophotometrically [79,95,96].

Stability Studies

Stability studies were conducted according to ICH guidelines at different storage conditions to evaluate physical appearance, pH, viscosity, and drug content [79,97,98,99].

RESULTS AND DISCUSSION

Preformulation Studies

Organoleptic Properties

The organoleptic properties of Hydrocortisone were evaluated visually to confirm its identity and purity before formulation development.

Table: Visual Inspection and Surface Morphology

Observation	Result
Color	White to off-white
Appearance	Homogeneous, smooth
Sedimentation	Absent
Morphology (SEM)	Spherical, porous

 

 

Figure: SEM of Hydrocortisone loaded Nanosponges

Drug Content and Entrapment Efficiency

 

Entrapment efficiency was determined using UV spectrophotometric analysis.

 

Discussion

No significant changes were observed in physical appearance, particle size, drug content, or entrapment efficiency after stability studies, indicating acceptable stability of the optimized hydrocortisone nanosponge hydrogel formulation.

CONCLUSION

The present study was undertaken with the objective of developing and evaluating a hydrocortisone nanosponges loaded hydrogel for topical delivery in the management of psoriasis. Psoriasis is a chronic inflammatory skin disorder that requires long-term therapy, and conventional topical formulations often suffer from limitations such as poor skin penetration, low bioavailability, frequent dosing, and associated side effects. Therefore, the development of an advanced drug delivery system capable of overcoming these limitations was considered essential.

In this research, hydrocortisone was selected as the model drug due to its well-established anti-inflammatory and immunosuppressive activity. The formulation strategy involved the preparation of nanosponges using the emulsion solvent diffusion method, followed by their incorporation into a Carbopol-based hydrogel. This dual delivery system was designed to achieve controlled drug release, enhanced skin retention, and improved therapeutic efficacy.

The nanosponges were successfully formulated with desirable physicochemical characteristics. The optimized formulation exhibited nanoscale particle size, uniform distribution, and porous morphology, which are essential for effective drug encapsulation and release. The entrapment efficiency was found to be satisfactory, indicating efficient incorporation of hydrocortisone within the nanosponge structure. These results confirmed that the selected method was suitable for the preparation of stable and efficient nanocarriers.

The incorporation of nanosponges into the hydrogel base was achieved without any compatibility issues. The prepared hydrogel exhibited acceptable physical properties, including smooth texture, good homogeneity, appropriate viscosity, and excellent spreadability. The pH of the formulation was found to be within the acceptable range for topical application, ensuring minimal risk of skin irritation. These characteristics indicate that the formulation is patient-friendly and suitable for dermal use.

In-vitro drug release studies demonstrated that the nanosponge formulation provided a controlled release profile, which was further prolonged upon incorporation into the hydrogel. The release pattern showed sustained drug delivery over an extended period, with no significant burst release observed. This behavior can be attributed to the porous structure of nanosponges, which act as reservoirs for the drug, and the hydrogel matrix, which provides an additional barrier to drug diffusion. Such a sustained release profile is highly beneficial in reducing the frequency of application and improving patient compliance.

The drug release kinetics analysis indicated that the release mechanism followed diffusion-controlled behavior, best described by the Higuchi and Korsmeyer–Peppas models. This suggests that the drug release is governed by a combination of diffusion and matrix-controlled mechanisms, which is ideal for achieving sustained therapeutic action.

Stability studies conducted under accelerated conditions demonstrated that the formulation remained stable with minimal changes in drug content and physical properties over time. This confirms the robustness and suitability of the formulation for long-term storage and practical use.

Overall, the findings of the study clearly indicate that the hydrocortisone nanosponges loaded hydrogel is a promising and effective topical drug delivery system. The formulation successfully addresses the limitations of conventional therapies by providing controlled drug release, enhanced skin permeation, improved stability, and better patient compliance. The integration of nanosponges with a hydrogel base offers a synergistic effect, resulting in a dual-controlled release system that enhances therapeutic performance.

In conclusion, the developed formulation represents a significant advancement in topical drug delivery for psoriasis management. It has the potential to improve treatment outcomes, reduce side effects, and enhance patient adherence. The study provides a strong foundation for further research and development in this area and supports the application of nanotechnology-based systems in dermatological therapy.

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