Supramolecular Dissolving Microneedle Patch Loading Hydrophobic Glucocorticoid for Effective Psoriasis Treatment

Abstract

Glucocorticoid-based creams are commonly used for treatments of psoriatic skin lesions while showing poor permeation because the thickened stratum corneum severely limits drug absorption. Although dissolving microneedle (DMN) patches have been employed in treating skin disease by virtue of their direct target to the lesion site, conventional DMN patches are generally fabricated from the water-soluble matrix, making them difficult to efficiently encapsulate hydrophobic glucocorticoids. Here, we develop a mechanically robust supramolecular DMN composed of hydroxypropyl β-cyclodextrin (HPCD) to effectively and uniformly load triamcinolone acetonide (TA). The TA-loaded HPCD DMN (TAMN) exhibits excellent mechanical performance that can easily pierce the thickened psoriasis lesions and deliver TA efficiently. Owing to the increased water solubility and bioavailability of TA after inclusion into HPCD, TAMN shows a superior in vitro inhibitory effect on immortalized human keratinocyte (HaCaT) cells. Importantly, the administration of TAMN twice a week effectively alleviates psoriatic signs and reduces the expression of Ki67, IL-23, and IL-17 in the ear lesions of imiquimod-induced psoriasis-like mice. This supramolecular DMN provides a promising strategy for the efficient treatment of psoriasis and other skin diseases, greatly broadens the applications of supramolecular materials in transdermal drug delivery, and widens the range of drugs in DMNs.

Microneedles Patch: Design, Fabrication and Applications

“…Vaccine delivery [316] Hollow microneedles Insulin Vaccine delivery [317] Dissolving microneedle patches Heat-inactivated bacteria Vaccine delivery [318] Solid pyramidal microneedle Stabilized HIV envelope trimer immunogen and adjuvant Vaccine delivery [319] Microneedle patches Acetyl-hexapeptide-3 Wrinkle [283] Stainless solid microneedles 5-fluorouracil Keloids [320] Poly(ionic liquid)-based microneedle patches Salicylic acid Acne [321] Dissolvable hyaluronic acid microneedles Shikonin Hypertrophic scars [322] Methacrylate gelatin/polyethylene glycol diacrylate double-network hydrogel microneedle patch Betamethasone Hypertrophic scars [323] Dissolving microneedle array MiRNA-modified functional exosomes Hypertrophic scars [324] Dissolving gelatin and starch microneedle patches Losartan Hypertrophic scars [325] Dissolving microneedle Triamcinolone acetonide Psoriasis [326] Dissolving microneedle patches Tetramethylpyrazine Rheumatoid arthritis [327] Hydrogen peroxideresponsive microneedle Integrin αvβ6-blocking antibody Pulmonary fibrosis [328] Dissolvable microneedles Dexamethasone Atopic dermatitis [329] Natural antimicrobial material microneedles Peony leaf extract Chronic wounds [330] Hyaluronic…”

Mechanically Robust Dissolving Microneedles Made of Supramolecular Photosensitizers for Effective Photodynamic Bacterial Biofilm Elimination

“…Mechanically robust dissolving microneedle (DMN) patch can penetrate the compact EPS barrier of biofilms to deliver antibacterial agents effectively, thus showing great promise for eliminating biofilms. − Herein, for the first time, we developed a DMN patch composed of a supramolecular photosensitizer (SP) for enhanced penetration and photodynamic elimination of bacterial biofilms (Scheme ). Tetra­(4-pyridyl)-porphine (TPyP), a commonly used porphyrin derivative, was successfully included into sulfobutylether-β-cyclodextrin (SCD) through supramolecular interactions.…”

Type I Photosensitizer Targeting Glycans: Overcoming Biofilm Resistance by Inhibiting the Two‐Component System, Quorum Sensing, and Multidrug Efflux

“…This oxidative onslaught leads to irreversible bacterial death and probably immunity response simultaneously with the advantages of minimal drug resistance, diminished systemic toxicity, and fewer side effects. [ 32–34 ] Although many PSs have shown efficacy against planktonic bacteria, [ 35–37 ] the broader application of PDT in biofilm eradication is constrained by the biofilm's hypoxic microenvironment and EPS penetration. [ 22,38–44 ]…”

“…This oxidative onslaught leads to irreversible bacterial death and probably immunity response simultaneously with the advantages of minimal drug resistance, diminished systemic toxicity, and fewer side effects. [32][33][34] Although many PSs have shown efficacy against planktonic bacteria, [35][36][37] the broader application of PDT in biofilm eradication is constrained by the biofilm's hypoxic microenvironment and EPS penetration. [22,[38][39][40][41][42][43][44] The electronegative properties of plasma membranes and EPS make positively charged materials, such as cationic polypeptides and quaternary ammonium compounds, particularly effective at enhancing biofilm penetrability through electrostatic interactions.…”