# Novel Small-Molecule Treatment and Emerging Biological Therapy for Poriasis
## 2 Small Molecules
### Corticosteroids
#### 2.1.2 Microneedles  
Microneedles (MNs) are miniature needles that typically measure between tens and thousands of micrometers in length. MNs are engineered to physically penetrate the outer barrier (stratum corneum), thereby providing the channel for drug delivery. Compared with traditional hypodermic injections, MNs provide a minimally invasive transdermal delivery method, making them a promising option, particularly for managing chronic conditions. Their versatility in material selection and design enables precise dosage control and flexibility in drug delivery. MNs facilitate targeted drug release, enhance biodistribution, and minimize drug loss caused by systemic circulation, degradation, clearance, or tissue diffusion. They hold significant potential for treating various skin disorders, including acne, atopic dermatitis, psoriasis, and skin cancer, by enabling targeted immunomodulatory delivery to skin-resident immune cells [40].  
Recently, [PERSON] et al. used microneedles as the reservoir for liposomes. Their study examined how the liposomes' physiochemical properties (such as size and potential) (Figure 1C-E) influence skin retention and cell internalization. Their findings revealed that 100 nm anionic liposomes achieved higher cellular absorption, whereas larger anionic liposomes (200 nm and 450 nm) improved skin retention and extended drug release within the body. Additionally, converting the surface charge of 250 nm anionic liposomes into cationic liposomes can further improve cell uptake. Indocyanine green-loaded liposomes revealed that cationic liposomes can prolong the fluorescence signal in the skin by 132 h (Figure 1F). Finally, dexamethasone was encapsulated in optimized liposomes for administration. Compared with the model group, symptoms were significantly relieved, and epidermal thickening was reduced [34]. However, most water-soluble microneedles have difficulty in effectively trapping hydrophobic glucocorticoids. Here, [PERSON] et al. utilized hydroxypropyl-\(\beta\)-cyclodextrinrin to form a water-soluble inclusion complex with triamcinolone acetonide, and this complex was used to construct a supramolecular microneedle (TAMN) with low shrinkage and rapid dissolution properties. The microneedles effectively penetrated the thickened outer skin layer of IMQ-treated mice, achieving a depth of 300 \(\upmu\)m, and successfully delivered triamcinolone acetonide to the targeted region. Histopathological analysis revealed that the use of TAMN reduced the epidermal thickness of imiquimod-treated ears from 111 \(\pm\) 5.59 \(\upmu\)m to 34.53 \(\pm\) 0.87 \(\upmu\)m. Additionally, it significantly decreased the expression of Ki67, which is indicative of keratinocyte proliferation and reflects the severity of psoriasis [41]. [PERSON] et al. designed a multi-functional structured color triboelectric microneedle patch (SMP) made from budesonide-coated polyacrylamidepolyethylene glycolacrylate-lithium chloride (PAM-PEGDA-LiCI) ionic hydrogel with an anti-opal micromeedle structure. The release of budesonide is driven by the electric charge generated from the friction between the ionic hydrogel and the skin, known as a triboelectric nanogenerator (TENG). This mechanism enables controlled drug release through continuous self-powered stimulation [42].