*6.7. Hydrogels Loaded with Nanoemulsion*

Genistein (GEN) is an isoflavone that has recently received a lot of attention because of its effects on avoiding skin carcinoma and dermal aging on exposure to ultraviolet light. Due to its poor aqueous solubility, it cannot incorporate it into a topically applied form. To improve the solubility and permeability, Vargas et al. [56] created topical hydrogels encapsulated in GEN nanoemulsions. CAR-940-based hydrogel containing GEN-NE penetrates the skin in a sustained manner. They concluded that compared to octyldodecanol, there was detected a higher amount of GEN in the skin from the formulation composed of medium chain triglycerides (MCT) as the oily core. It is a promising delivery system for the skin.

### *6.8. Hydrogel Loaded with Cubosomes*

The higher concentration of surfactant affects the size of the particle, entrapment efficiency of API, release from the formulation, and causes an adverse or toxic effect to the body. To overcome the above-mentioned drawbacks, Rapalli et al. [59] used the 'Quality by Design (QbD) method to create a topical hydrogel comprising ketoconazole (KETO) entrapped cubosomes with lesser surfactant concentrations. They were successful in their research, using the QbD method, by formulating the KETO-CUBO with a lower amount of surfactant than those reported in previous works of literature.

### *6.9. Hydrogel Loaded with Nanosponge*

Nanosponge (NS) is a novel preparation that is a nanoporous carrier with a spongelike network shaped by hyper cross-linking polymeric materials to form three-dimensional covalent structures used to incorporate nanoparticles with a non-collapsible and porous formation [69,70]. Clobetasol propionate (CP), a potent topical corticosteroid, possesses a high therapeutic potential for psoriasis. Meanwhile, common adverse effects, such as skin degeneration, steroidal acne, skin discoloration, and allergic skin reactions, limit its utility for topical administration. Kumar et al. [60] created a CP-NS based on these observations. They incorporated it into a CAR-934 hydrogel to reduce the adverse effects and control the CP release. They successfully prepared cyclodextrin-based CP-NS, with approximately 86% of CP released after 24 h. Incorporating CP-NS with CAR-934 hydrogel enhanced its suitability for topical administration. The anti-psoriatic potential of fabricated nanoformulation was further substantiated in vivo using a mouse tail model. Histological and biochemical findings showed appreciable anti-psoriatic activity of the prepared nanogel.

### **7. Conclusions**

The formulations' main goal is to deliver the APIs effectively, and to be toxicity-free and long-lasting. The novel formulations have benefits over traditional formulations, such as improved solubility, bioavailability, toxicity protection, improved pharmacological action, stability improvement, better tissue macrophage dispersion, sustained delivery, and protection from physiochemical deterioration. Incorporation of different APIs into novel formulations like nanoparticles, nanocapsules, liposomes, phytosomes, nanoemulsions, microemulsions, cubosomes, SLNP, NLC, nanosponge, and other novel formulations fulfill the above benefits.

Common skin diseases normally necessitate topical preparations to ensure patient compliance, while causing negligible systemic adverse effects. Treating skin diseases with a simple semi-solid dosage form is an appealing goal for dermatologists, patients, and pharmaceutical companies alike. The most significant challenge in achieving this goal is attaining adequate drug penetration, while reducing side effects. Numerous obstacles exist in the treatment of the skin on a topical basis. As an outcome, drug delivery through the skin is extremely complicated. Detailed physical and chemical properties and delivery systems are needed to estimate and analyze topical preparation and improve particle properties. In several cases, in vitro, ex vivo, and in vivo animal studies are the best method to study drug penetration and analyze the clinical efficiency and effectiveness of novel topical drugs delivery systems.

Hydrogels have been extensively used in topical applications because of their excellent biocompatibility, solubility in water, and three-dimensional pore structure that fits the extracellular matrix. Hydrogel research based on sources (mainly natural and synthetic polymers) has recently gained attraction that showed outstanding physicochemical properties that could be useful in treating a wide range of skin diseases. This innovation could allow for the localized delivery of APIs via topical applications to increase the action. There has been an increase in research on novel hydrogels over the last decade. Novel hydrogels were able to enhance the penetration of APIs, minimizing the risks of percutaneous absorption. These novel hydrogels have a strong pharmacological effect against different skin diseases. The combination of novel formulations with hydrogels offers a great opening to treat several currently available skin diseases. In this review, we learned that many researchers formulated novel formulations and a few did not conduct many characteristic studies (particle size, shape, entrapment efficacy, zeta potential, viscosity, pH, in-vitro release studies, etc.) for the prepared novel formulations. The novel formulation was then

primarily mixed with hydrogel preparations. All of the researchers then carried out the evaluation studies for the novel hydrogel formulation by the studies. As evidenced by animal studies, many novel hydrogels demonstrated significant activity against various topical diseases and found this one to be stable, as evidenced by stability studies. There is a strong possibility that novel hydrogels based on natural and synthetic polymers will soon enter clinical trials and the market.

**Funding:** No funding to declare.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Conflicts of Interest:** The authors declare no conflict of interest.

### **Abbreviations**

