# Novel Small-Molecule Treatment and Emerging Biological Therapy for Poriasis
## 2 Small Molecules
### Corticosteroids
#### Micro/Nanocarrier-Loaded Hydrogels
The preparation was under heating conditions and formed a gel upon cooling to room temperature (Figure 1A). About 50% of the betamethasone was released within one day in the release experiment, with no significant outburst release observed. The Franz cell diffusion shows \(>\)95% betamethasome skin permeation after 1 day (Figure 1B). In the IMQ-induced mouse model (ear), after one treatment cycle, B-gel reduced the overall PASI score from 12 to 2, which is comparable to the reduction achieved by the clinically used betamethasone valerate cream, which also lowered the PASI score from 12 to 2. Flow cytometry analysis of ear skin tissue samples revealed that B-gel achieves a 2.5-fold decrease in leukocyte (CD45+ cell) infiltration in comparison with untreated samples. This result was further corroborated using immunofluorescence staining [31]. [PERSON] et al. reported a microsponge that was designed as the carrier of clobetasol propionate (CP) and encapsulated into carbomer gel. The results of drug release experiments revealed that the microsponge-loaded gel achieved sustained release for up to 9 h, with the release behavior following zero-order kinetics. This significantly minimizes the side effects and skin irritation associated with the burst release of CP [32]. [PERSON] et al. combined fluocinonide acetate (FA) with nano-lipid carriers (NLCs). They embedded the NLCs in a gel containing salicylic acid (FSG) and prepared a gel containing both plain FA and salicylic acid (PFSG) as a control. The findings indicated that FSG exhibited a significantly prolonged release duration compared with PFSG. Specifically, the FA release period for FSG was extended beyond 24 h, whereas the PFSG formulation achieved over 90% FA release in less than 7 h. According to the quantitative results, in the stratum comeum, the FA content in the FSG group was 1, while in the PFSG group, it was 0.5. In the viable layer, the FSG group was 1.7, compared with 0.6 in the PFSG group (\(\upmu\)g/0.64 cm\({}^{2}\)). The results indicate that NLCs enabled FA to penetrate the skin better. The ELISA results of skin samples showed that, compared with the positive control (IMQ-induced mouse), the levels of TNF-\(\upalpha\) in the FSG and PFSG groups decreased by 1.81- and 1.2-fold, respectively. The concentrations of IL-17 were reduced by 1.84- and 1.14-fold, while IL-22 levels decreased by 2.1- and 1.3-fold, respectively. These results suggest that NLC loading enhanced the local delivery efficiency of FA and salicylic acid [33]. Iontophoresis can improve local drug permeation through the _Stratum corneum_[36]. A dual-drug co-release patch, powered by an integrated magnesium battery, employs a hydrogel with an ionic hyperbranched poly (amidoamine) dendrimer, serving as both the cathode and drug reservoir. This patch can hold the release of dexamethasone (Dex) and tannic acid (Ta) in a controlled way, overcoming the limitation of a single treatment and the risk of sudden release. When a 1 k\(\Omega\) resistor was loaded, the cumulation of drug release was 44.3% of Ta and 40.5% of Dex. Both drugs were released as intended, and the  
Figure 1: **(A)** Solution to the gel phase transition of B-gel. **(B)** In vitro release profile of betamethasone loaded in B-gel. Reproduced with permission from Ref. [31]. **(C)** The size distribution of different liposomes. **(D)** The size distribution of different DOTAP content liposomes. **(E)** The Zeta potential of different liposomes. **(F)** In vivo NIR-II fluorescence imaging of 60% DOTAP-lip. From black to white, the color bar reflects the intensity of fluorescence from weak to strong. Reproduced with permission from Ref. [34]. **(G)** The thermal imaging shows that AuNR-DX was photoactivated using near-infrared lasers (excitation wave: 808 nm). From blue to red, the temperature reflects from low to high. **(H)** The quantitative results of temperature variation in laser-activated nanorods. **(I)** Photoactivation promoted the Dex release in simulated cellular conditions. Reproduced with permission from Ref. [35].