Yadav Krishna, Singh Deependra, Singh Manju Rawat, Pradhan Madhulika
University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur 492010, India.
Rungta College of Pharmaceutical Sciences and Research, Kohka, Bhilai 490024, India.
Med Hypotheses. 2020 Dec;145:110322. doi: 10.1016/j.mehy.2020.110322. Epub 2020 Oct 2.
Psoriasis is a chronic autoimmune disorder that affects the skin to alter its structure and physiology and express the phenotypic function of abnormal epidermal cell growth through a cascade of molecular, and cellular intervention. The histological changes in skin include inflammation, scaling, hyperproliferation of epidermis resulting in thickening of the skin, under the influence of altered immunopathogenesis. The zone of activity for the therapeutic targeting of psoriasis is viable epidermis involving various cellular events regulating the whole progression of the disease manifestation. Therefore, therapeutic targeting of psoriasis through the systemic route would be imprecise and associated with numerous side effects. Small interfering RNA (siRNA) molecules have emerged as a powerful class of therapeutics for treating psoriasis. However, successful targeted delivery of necked siRNA into the skin is hampered due to physicochemical features, proneness to enzymatic degradation, and unavailability of effective delivery carriers. The steroidal medications are the most preferred choice among existing conventional topical formulations; however, they also have their drawbacks like poor aqueous solubility, deprived drug penetration across the skin, reduced half-life, dose-dependent side effects, and reduced patient compliance. In the present study, we hypothesize the development of a liposomal gel formulation for co-delivery of siRNA (siRNA against IL-17A) and a steroidal drug (Clobetasol propionate) to target different pathogenic events of psoriasis leading to the accomplishment of synergistic therapeutic effect. Since a sequence of events simultaneously occurs during the pathogenesis of psoriasis, synergistic blends of siRNA and corticosteroid would ensure a multi-targeted treatment that would act through a diverse range of mechanisms, ultimately leading to the enhancement of therapeutic effect. Therefore, exploiting the full therapeutic potential of these therapeutics. Thus, the present work suggests a novel, innovative, and promising idea for accomplishing effective treatment of psoriasis.
银屑病是一种慢性自身免疫性疾病，它会影响皮肤，改变其结构和生理功能，并通过一系列分子和细胞干预来表达异常表皮细胞生长的表型功能。在免疫发病机制改变的影响下，皮肤的组织学变化包括炎症、脱屑、表皮过度增殖导致皮肤增厚。银屑病治疗靶点的活性区域是涉及调节疾病表现整个进程的各种细胞事件的活表皮。因此，通过全身途径对银屑病进行治疗靶向将不准确且伴有许多副作用。小干扰RNA（siRNA）分子已成为治疗银屑病的一类强大的治疗药物。然而，由于其物理化学特性、易于酶降解以及缺乏有效的递送载体，将裸siRNA成功靶向递送至皮肤受到阻碍。甾体药物是现有传统局部制剂中最优选的选择；然而，它们也有缺点，如水溶性差、药物经皮渗透不足、半衰期缩短、剂量依赖性副作用以及患者依从性降低。在本研究中，我们假设开发一种脂质体凝胶制剂，用于共同递送siRNA（针对IL-17A的siRNA）和一种甾体药物（丙酸氯倍他索），以靶向银屑病的不同致病事件，从而实现协同治疗效果。由于在银屑病发病过程中一系列事件同时发生，siRNA和皮质类固醇激素的协同组合将确保通过多种机制起作用的多靶点治疗，最终导致治疗效果增强。因此，充分发挥这些治疗药物的全部治疗潜力。因此，目前的工作为实现银屑病的有效治疗提出了一个新颖、创新且有前景的想法。
