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To reduce mucosal damage in the gastrointestinal tract caused by aspirin, we developed a dissolvable polymeric microneedle (MN) patch loaded with aspirin. Biodegradable polymers provide mechanical strength to the MNs. The MN tips punctured the cuticle of the skin and dissolved when in contact with the subcutaneous tissue. The aspirin in the MN patch is delivered continuously through an array of micropores created by the punctures, providing a stable plasma concentration of aspirin. The factors affecting the stability of aspirin during MNs fabrication were comprehensively analyzed, and the hydrolysis rate of aspirin in the MNs was less than 2%. Compared to oral administration, MN administration not only had a smoother plasma concentration curve but also resulted in a lower effective dose of antiplatelet aggregation. Aspirin-loaded MNs were mildly irritating to the skin, causing only slight erythema on the skin and recovery within 24 h. In summary, aspirin-loaded MNs provide a new method to reduce gastrointestinal adverse effects in patients requiring aspirin regularly. [ABSTRACT FROM AUTHOR]

Coated microneedles (MNs) are widely used for delivering biopharmaceuticals. In this study, a novel gel encapsulated coated MNs (GEC-MNs) was developed. The water-soluble drug coating was encapsulated with sodium alginate (SA) in situ complexation gel. The manufacturing process of GEC-MNs was optimized for mass production. Compared to the water-soluble coated MNs (72.02% ± 11.49%), the drug delivery efficiency of the optimized GEC-MNs (88.42% ± 6.72%) was steadily increased, and this improvement was investigated through in vitro drug release. The sustained-release of BSA was observed in vitro permeation through the skin. The rhIFN α-1b GEC-MNs was confirmed to achieve biosafety and 6- month storage stability. Pharmacokinetics of rhIFN α-1b in GEC-MNs showed a linearly dosedependent relationship. The AUC of rhIFN α-1b in GEC-MNs (4.51 ng/ml ·h) was bioequivalent to the intradermal (ID) injection (5.36 ng/ml ·h) and significantly higher than water-soluble coated MNs (3.12 ng/ml ·h). The rhIFN α-1b elimination half-life of GEC-MNs, soluble coated MNs, and ID injection was 18.16, 1.44, and 2.53 h, respectively. The complexation-based GECMNs have proved to be more efficient, stable, and achieve the sustained-release of watersoluble drug in coating MNs, constituting a high value to biopharmaceutical. [ABSTRACT FROM AUTHOR]

In recent years, as a new trans dermal drug delivery method, microneedle trans dermal drug delivery technology accelerates the absorption of drugs through micron pores, which has been widely used in the field of medicine and cosmetics. Dissolving microneedles have the characteristics of good biocompatibility and fast dissolution speed, which attract more and more res earc hers, attention and research. In this paper, the concept, properties and preparation methods of dissolving mi-crone edles as well as the research status of dissolving microneedles in the field of medicine and cosmetics in recent years were summarized and prospected, so as to enable researchers to have a clearer and comprehensive understanding of dissolving microneedles and prospect the application and development prospects of dissolving microneedles in the industry. [ABSTRACT FROM AUTHOR]

The development of organs with an epithelial parenchyma relies on reciprocal mesenchymal-epithelial communication. Mouse corneal epithelium stratification is the consequence of a coordinated developmental process based on mesenchymal-epithelial interactions. The molecular mechanism underlying these interactions remains unclear. The Wnt/β-catenin signaling pathway is involved in fundamental aspects of development through the regulation of various growth factors. Here, we show that conditional ablation of either β-catenin (Ctnnb1cKO) or co-receptors Lrp5/6 (Lrp5/6cKO) in corneal stromal cells results in precocious stratification of the corneal epithelium. By contrast, ectopic expression of a murine Ctnnb1 gainof- function mutant (Ctnnb1cGOF) retards corneal epithelium stratification. We also discovered that Bmp4 is upregulated in the absence of β-catenin in keratocytes, which further triggers ERK1/2 (Mapk3/1) and Smad1/5 phosphorylation and enhances transcription factor p63 (Trp63) expression in mouse corneal basal epithelial cells and in a human corneal epithelial cell line (HTCE). Interestingly, mouse neonates given a subconjunctival BMP4 injection displayed a phenotype resembling that of Ctnnb1cKO. Conditional ablation of Bmp4 eradicates the phenotype produced in Ctnnb1cKO mice. Furthermore, ChIP and promoter-luciferase assays show that β-catenin binds to and suppresses Bmp4 promoter activity. These data support the concept that cross-talk between the Wnt/β-catenin/ Bmp4 axis (in the stromal mesenchyme) and Bmp4/p63 signaling (in the epithelium) plays a pivotal role in epithelial stratification during corneal morphogenesis. [ABSTRACT FROM AUTHOR]