Wound healing is a multifaceted biological process influenced by both intrinsic and extrinsic factors. The ability of Wnt signaling to activate cell proliferation appears to serve a central role in wound healing. Therefore, the direct activation of Wnt or inhibition of the Wnt antagonist could be an ideal approach for the stimulation of wound healing. This study aimed to investigate the underlying mechanism of small molecule-loaded nanofibrous matrix in inducing wound healing. Herein, a naturally derived small molecule, curcumin, was used to inhibit the GSK3-β, which is considered a negative regulator of the Wnt/β-catenin signaling pathway. The docking results demonstrated that curcumin makes a complex with GSK3-β at seven specific sites, thereby inhibiting its activity. Moreover, the stabilization of β-catenin appeared to be increased with the treatment of curcumin. Next, curcumin was incorporated in poly ε-caprolactone nanofibrous matrices for controlled–sustained drug release to induce cell function. Curcumin-loaded nanofibrous matrix not only enhanced fibroblast cell proliferation, but also induced the expression of the fibroblast growth factor (FGF) in vitro. Moreover, the in vivo results showed that these nanofibrous mats significantly induced wound closure in 12 mm critical-sized defect. Collectively, these results suggest that the developed nanofibrous matrix promotes impaired wound healing by modulating cell proliferation and enhancing FGF expression that promotes wound closure.

Levosulpiride is a widely used gastroprokinetic agent in the treatment of various gastric disorders; however, its short half-life and increased dosage frequency leads to non-compliance and possible adverse effects. The prime objective of the current study was to develop a sustained-release formulation of Levosulpiride incorporating bioresorbable cellulose derivatives. Sustained-release formulations of Levosulpiride were prepared through direct compression using various cellulose derivatives such as CMC sodium, HPC, and HPMC in different polymer-to-drug weight ratios as release-modifying polymers. The powder blends and compressed tablets were then subjected to pre-compressional and post-compressional evaluation, as well as FTIR analysis. In vitro release studies were performed for all formulations of the model drug in buffer solution of pH 6.8 at a wave length of 214 nm by a UV-visible light spectrophotometer. The FTIR results confirmed that the interaction between components was physical, and from the different kinetic models data, the release profile was best expressed by the Higuchi model because the results showed high linearity. The results also showed formulation F9 to be the ideal one among the developed formulations, exhibiting sustained- release behavior. Levosulpiride sustained-release matrices were prepared successfully using CMC sodium, HPC, and HPMC as the release-retarding polymer/carrier.

Pulp-Dentin regeneration is a key aspect of maintain tooth vitality and enabling good oral-systemic health. This study aimed to investigate a nanofibrous scaffold loaded with a small molecule i.e. Tideglusib to promote odontogenic differentiation. Tideglusib (GSK-3β inhibitor) interaction with GSK-3β was determined using molecular docking and stabilization of β-catenin was examined by confocal microscopy. 3D nanofibrous scaffolds were fabricated through electrospinning and their physicochemical characterizations were performed. Scaffolds were seeded with mesenchymal stem cells or pre-odontoblast cells to determine the cells proliferation and odontogenic differentiation. Our results showed that Tideglusib (TG) binds with GSK-3β at Cys199 residue. Stabilization and nuclear translocation of β-catenin was increased in the odontoblast cells treated with TG. SEM analysis revealed that nanofibers exhibited controlled architectural features that effectively mimicked the natural ECM. UV-Vis spectroscopy demonstrated that TG was incorporated successfully and released in a controlled manner. Both kinds of biomimetic nanofibrous matrices (PCLF-TG100, PCLF-TG1000) significantly stimulated cells proliferation. Furthermore, these scaffolds significantly induced dentinogenic markers (ALP, and DSPP) expression and biomineralization. In contrast to current pulp capping material driving dentin repair, the sophisticated, polymeric scaffold systems with soluble and insoluble spatiotemporal cues described here can direct stem cell differentiation and dentin regeneration. Hence, bioactive small molecule-incorporated nanofibrous scaffold suggests an innovative clinical tool for dentin tissue engineering.

Diklofenak, bir fenilasetik asit türevi olup uzun yıllardan beri antienfamatuvar ve analjezik bir ilaç olarak kullanılmaktadır ancak bu etken maddeden hareketle hemen salım için yükleme dozu içeren geciktirilmiş salım formülasyonunun hazırlanması istenmektedir. Bu çalışmanın amacı, ağızda dağılan tabaka olarak diklofenak potasyum, geciktirilmiş salım çekirdeği olarak diklofenak sodyum içeren iki tabakalı tabletlerin formülasyonu ve değerlendirilmesidir. Diklofenak sodyum içeren çekirdek yaş granülasyon yöntemi ile hazırlanırken ağızda dağılan dış tabaka direct basım yöntemiyle ve süper dağıtıcı olarak sodyum nişasta glikolat varlığında hazırlandı. Toz karışımı hem basım öncesi hem de basım sonrası özellikleri açısından değerlendirildi. Toz karışımının ve tabletlerin fiziksel özelliklerinin zorunlu standartlarla uyumlu olduğu görüldü. Ağızda dağılan kısmın 30 saniyeden kısa bir sürede dağılarak yükleme dozu olan diklofenak potasyumu saldığı, çekirdek kısmının ise simule bağırsak sıvısında (pH 6.8), 10 saate kadar diklofenak sodyum salınımı sağladığı tespit edildi. Kinetik ile ilgili veriler incelendiğinde, tabletin non-fickian salım gösterdiği ve Korsmeyer-Peppas modeline uygun olduğu tespit edildi. Tek bir tablet içeriğinde, ağızda dağılan tabaka olarak diklofenak potasyum, geciktirilmiş salım çekirdeği olarak diklofenak sodyum içeren ve süper dağıtıcı olarak sodyum nişasta glikolat içeren tabletlerin formülasyonu başarıyla yapıldı.