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.

Dissolving microneedle (DMN) patches are emerging as a minimally invasive and efficient transdermal drug delivery platform. Generally, noncrystalline, water-soluble, and high-molecular-weight polymers are employed in DMNs because their sufficient intermolecular interactions can endow the DMNs with necessary mechanical strength and toughness. However, high viscosity and heavy chain entanglement of polymer solutions greatly hinder processing and dissolution of polymeric DMNs. Here, a strong and tough supramolecular DMN patch made of highly water-soluble cyclodextrin (CD) derivatives is described. Due to the synergy of multiple supramolecular interactions, the CD DMN patch exhibits robust mechanical strength outperforming the state-of-the-art polymeric DMNs. The CD DMN displays ultrafast dissolution (<30 s) in skin models by virtue of the dynamic and weak noncovalent bonds, which also enables the CD DMN and its payloads to diffuse rapidly into the deep skin layer. Moreover, the unique supramolecular structure of CD allows the CD DMNs to load not only hydrophilic drugs (e.g., rhodamine B as a model) but also hydrophobic model drugs (e.g., ibuprofen). As a proof-of-concept, CD DMNs loading ibuprofen show a rapid onset of therapeutic action in a xylene-induced acute inflammation model in mice. This work opens a new avenue for the development of mechanically robust supramolecular DMNs and broadens the applications of supramolecular materials.

Wound infection can cause a delay in wound healing or even wound deterioration, threatening patients' lives. The excessive accumulation of reactive oxygen species (ROS) in infected wounds activates a strong inflammatory response to delay wound healing. Therefore, it is highly desired to develop hydrogels with inherent antimicrobial activity and antioxidant capability for infected wound healing. Herein, a dopamine-substituted multidomain peptide (DAP) with inherent antimicrobial activity, strong skin adhesion, and ROS scavenging has been developed. DAP can form bilayer β-sheets with dopamine residues on the surface of nanofibers. The enhanced rheological properties of DAP-based hydrogel can be achieved not only through UV irradiation but also by incorporation of multivalent ions (e.g., PO43-). Furthermore, the DAP hydrogel shows a broad spectrum of antimicrobial activity due to the high positive charges of lysine residues and the β-sheet formation. When applied to full-thickness dermal wounds in mice, the DAP hydrogel results in a significantly shortened inflammatory stage of the healing process because of its remarkable antimicrobial activity and antioxidant capability. Accelerated wound closure with thick granulation tissue, uniform collagen arrangement, and dense vascularization can be achieved. This work suggests that the DAP hydrogel can serve as antimicrobial coating and ROS-scavenging wound dressing for bacterial-infected wound treatment.

Antibiotics' abuse in bacteria-infected wounds has threatened patients' lives and burdened medical systems. Hence, antibiotic-free hydrogel-based biomaterials, which exhibit biostability, on-demand release of antibacterial agents, and long-lasting antimicrobial activity, are highly desired for the treatment of chronic bacteria-infected wounds. Herein, we developed a hyaluronic acid (HA)-based composite hydrogel, with an antimicrobial peptide [AMP, KK(SLKL)3KK] as a cross-linking agent through Schiff's base formation, which exhibited an acidity-triggered release of AMP (pathological environment in bacteria-infected wounds, pH ∼ 5.5-5.6). During the self-assembly process, AMP adopted an antiparallel β-sheet secondary structure due to the alternate arrangement of hydrophobic and hydrophilic residues of amino acids. Owing to Schiff's base formation between the primary amines derived from lysine residues and the aldehydes in oxidized HA, the AMP-HA composite hydrogel exhibited injectability, high biostability, and enhanced mechanical strength. Importantly, both AMP and the AMP-HA composite showed excellent broad-spectrum antibacterial activity in vitro and in vivo. Specifically, the AMP-HA composite hydrogel exhibited on-demand full thickness wound healing in an infected mice model. Therefore, this work provides an efficient strategy to fabricate antibiotic-free hydrogel-based biomaterials for the management of chronic bacteria-infected wounds.

Porous polymer microneedles (MNs) with interconnected structures demonstrate great potential in dermal interstitial fluid (ISF) extraction. However, the fluid extraction rate and the recovery of the extracted ISF by the porous MNs are limited by the poor hydrophilicity and the adhesion of porous MNs. Herein, we present a facile and mild polydopamine (PDA) and poly(ethylene glycol) (PEG) coating strategy for hydrophilic and anti-adhesive modification of porous polymer MNs from a phase inversion method. As a proof-of-concept, taking polysulfone (PSF) as an example, PDA and PEG-coated MNs (PSF@PDA@PEG) are fabricated through the self-polymerization of dopamine and PEG anchoring. Thanks to the hydrophilicity and anti-adhesion of PEG, the resulting PSF@PDA@PEG MNs demonstrate improved hydrophilicity, fast fluid extraction speed, and low target molecular adhesion. Besides, this method can be extended to hydrophobic polymers generally used in medical fields, including polylactic acid (PLA), polyvinylidene fluoride (PVDF), etc. This investigation provides a new road for MN-based off-line analysis in point-of-care testing (POCT).

Porous polymer microneedles (MNs) have great potential in transdermal medical applications due to their three-dimensional (3D) porous structures and high porosity. However, existing approaches for the fabrication of such porous polymer MNs are complicated and only applicable to limited types of polymers. Here, we describe a facile yet effective phase inversion route to prepare polymer MNs with highly porous and interconnected pore structures. The fabrication process is simple and mild without involving high temperatures or irradiation, and can be applied to a broad spectrum of commonly used polymers (e.g., cellulose acetate (CA), polysulfone (PSF), polyethersulfone (PES), polylactic acid (PLA), etc.). Thanks to the capillary effect and large cavity given by highly porous and interconnected structures, the resulting porous polymer MNs show the capability of rapidly extracting dermal interstitial fluid (ISF) and efficiently loading/releasing drug compounds. As a proof of concept, we demonstrate the use of these porous CA MNs in the highly efficient extraction of ISF for glucose level detection and administration of insulin for hyperglycemia. Given the recent trend of painless techniques in diagnosis and treatment, the current study provides a new opportunity for the fabrication of MN-based devices for transdermal ISF extraction and drug delivery.

Rapamycin-loaded dissolving microneedles (RAPA DMNs) are fabricated by using polyvinylpyrrolidone (PVP) as the matrix and exhibit the good anti-angiogenic effect.

Hypertrophic scarring is a widespread skin disorder that affects a patient's confidence and quality of life.

5-Aminolevulinic acid (5-ALA) is one of the most widely used prodrug in clinical photodynamic therapy of dermatological diseases and cancers; yet, its clinical application is still limited by the shallow skin penetration and unsatisfied stability in any existed formulations. Here, 5-ALA-loaded hyaluronic acid dissolving microneedles (5-ALA@HAMNs) are prepared for photodynamic therapy of superficial tumors. The HAMNs can not only assist the loaded 5-ALA to effectively penetrate the stratum corneum but also provide 5-ALA with an acidic and oxygen-free environment to reduce the dimerization of 5-ALA molecules via Schiff-base bonds and formation of inactive pyrazine derivatives, thus maintaining its chemical structure and biological activity. The chemical stability of 5-ALA in HAMNs is confirmed by UV-vis spectra and mass spectra measurements. The 5-ALA@HAMNs display remarkable tumor elimination both in vitro and in vivo, even after storage at room temperature for nine months, making it a highly potential device for effective delivery of 5-ALA in cancer photodynamic therapy.

In this report, we present a facile approach to produce biodegradable polymeric microparticles with uniform sizes and controllable morphologies by blending hydrophobic poly(d, l-lactic-co-glycolide) (PLGA) and amphiphilic poly(d, l-lactic acid)-b-poly(ethylene glycol) (PLA-b-PEG) in a microfluidic chip. Microparticles with tentacular, hollow hemispherical, and Janus structures were obtained after complete evaporation of the organic solvent by manipulating the interfacial behavior of emulsion droplets and the phase separation behavior inside the droplets. The number and length of the tentacles on the surface of tentacular microparticles could be tailored by varying the initial concentration and blending ratios of the polymers. The organic solvent played an important role in controlling the morphologies of microparticles. For example, blending PLA16k-b-PEG5k with PLGA100k in dichloromethane resulted in tentacular microparticles, whereas hollow hemispherical microparticles were obtained in trichloromethane. Moreover, these microparticles with controllable shapes and surface textures have significant influence on the immune response of dendritic cells (DCs), showing a morphology-dependent enhancement of DC maturation.