Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Ave. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain; Department of Biomaterials and Biomedical Technology, The Personalized Medicine Research Institute (PRECISION), University Medical Center Groningen, University of Groningen. Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Ave. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
J Control Release. 2024 Nov;375:537-551. doi: 10.1016/j.jconrel.2024.09.032. Epub 2024 Sep 21.
Inflammatory diseases of the skin have a considerable high prevalence worldwide and negatively impact the patients' quality of life. First-line standard therapies for these conditions inherently entail important side effects when used long-term, particularly complicating the management of chronic cases. Therefore, there is a need to develop novel therapeutic strategies to offer reliable alternative treatments. Abnormally high reactive oxygen species (ROS) levels are characteristic of this kind of illnesses, and therefore a reasonable therapeutic goal. Cyanocobalamin, also known as Vitamin B, possesses notable antioxidant and ROS-scavenging properties which could make it a possible therapeutic alternative. However, its considerable molecular weight restricts passive diffusion through the skin and forces the use of an advanced transdermal delivery system. Here, we present several prototypes of Cyanocobalamin-loaded Dissolving Microarray Patches (B@DMAPs) with adequate mechanical properties to effectively penetrate the stratum corneum barrier, allowing drug deposition into the skin structure. Ex vivo penetration and permeability studies noted an effective drug presence within the dermal skin layers; in vitro compatibility studies in representative cell skin cell lines such as L929 fibroblasts and HaCaT keratinocytes ensured their safe use. The in vivo efficacy of the selected prototype was tested in a delayed-type hypersensitivity murine model that mimics an inflammatory skin process. Several findings such as a reduction of MPO-related photon emission in a bioluminescence study, protection against histological damage, and decrease of inflammatory cytokines levels point out the effectivity of B@DMAPs to downregulate the skin inflammatory environment. Overall, B@DMAPs offer a cost-effective translational alternative for improving patients' skin healthcare.
皮肤炎症性疾病在全球范围内具有相当高的患病率,对患者的生活质量产生负面影响。这些疾病的一线标准治疗方法在长期使用时固有地存在重要的副作用,特别是在管理慢性病例时更为复杂。因此,需要开发新的治疗策略,为患者提供可靠的替代治疗方法。这种疾病的一个特征是活性氧(ROS)水平异常升高,因此是一个合理的治疗目标。氰钴胺,也称为维生素 B,具有显著的抗氧化和 ROS 清除特性,使其成为一种可能的治疗选择。然而,其相当大的分子量限制了其通过皮肤的被动扩散,迫使使用先进的透皮递送系统。在这里,我们提出了几种载有氰钴胺的溶解微阵列贴剂(B@DMAPs)原型,这些原型具有足够的机械性能,可以有效地穿透角质层屏障,使药物沉积到皮肤结构中。体外穿透和渗透研究表明,药物有效地存在于皮肤的真皮层中;在代表性的皮肤细胞系(如 L929 成纤维细胞和 HaCaT 角质形成细胞)中的体外相容性研究确保了其安全使用。选定原型的体内功效在模拟炎症性皮肤过程的迟发型超敏反应小鼠模型中进行了测试。多项研究结果表明,生物发光研究中 MPO 相关光子发射减少、对组织学损伤的保护以及炎症细胞因子水平降低,都表明 B@DMAPs 能够下调皮肤炎症环境的有效性。总的来说,B@DMAPs 为改善患者的皮肤健康护理提供了一种具有成本效益的转化替代方案。