An overview of Skp2: a promising new therapeutic target of psoriasis.

INTRODUCTION: Psoriasis is a chronic immune-mediated disorder affecting over 2-3% of the population worldwide, significantly impacting quality of life. Despite the availability of various therapeutic interventions, concerns persist regarding lesion recurrence and potential alterations in immune surveillance promoting cancer progression. Recent advancements in understanding cellular and molecular pathways have unveiled key factors in psoriasis etiology, including IL-17, 22, 23, TNF-α, PDE-4, JAK-STAT inhibitors, and AhR agonists. This work explores the potential of S-phase kinase-associated protein 2 (Skp2) as a therapeutic target in psoriasis. AREA COVERED: This review covers the current understanding of psoriasis pathophysiology, including immune dysregulation, and the role of keratinocytes and ubiquitin. It also delves into Skp2 role in cell cycle regulation, and its correlation with angiogenesis and ubiquitin in psoriasis. The evolving therapeutic approaches targeting Skp2, including small molecule inhibitors, are also discussed. EXPERT OPINION: Targeting Skp2 holds promise for developing novel therapeutic approaches for psoriasis. By modulating Skp2 activity or expression, it may be possible to intervene in inflammatory and proliferative processes underlying the disease. Further research into Skp2 inhibitors and their efficacy in preclinical and clinical settings is warranted to harness the full potential of Skp2 as a therapeutic target in psoriasis management.

Exploring polysaccharide-based bio-adhesive topical film as a potential platform for wound dressing application: A review.

Wound dressings act as a physical barrier between the wound site and the external environment, preventing additional harm; choosing suitable wound dressings is essential for the healing process. Polysaccharide biopolymers have demonstrated encouraging findings and therapeutic prospects in recent decades about wound therapy. Additionally, polysaccharides have bioactive qualities like anti-inflammatory, antibacterial, and antioxidant capabilities that can help the process of healing. Due to their excellent tissue adhesion, swelling, water absorption, bactericidal, and immune-regulating properties, polysaccharide-based bio-adhesive films have recently been investigated as intriguing alternatives in wound management. These films also mimic the structure of the skin and stimulate the regeneration of the skin. This review presented several design standards and functions of suitable bio-adhesive films for the healing of wounds. Additionally, the most recent developments in the use of bio-adhesive films as wound dressings based on polysaccharides, including hyaluronic acid, chondroitin sulfate, dextran, alginate, chitosan, cellulose, konjac glucomannan, gellan gum, xanthan gum, pectin, guar gum, heparin, arabinogalactans, carrageen, and tragacanth gum, are thoroughly discussed. Lastly, to create a road map for the function of polysaccharide-based bio-adhesive films in advanced wound care, their clinical performances and future challenges in making bio-adhesive films by three-dimensional bioprinting are summarized.

Navigating the landscape of psoriasis therapy: novel targeted pathways and emerging trends.

INTRODUCTION: Psoriasis is a chronic, inflammatory, non-communicable skin disorder that affects a patient's social and emotional well-being. It is characterized by hyperproliferation of keratinocytes, irregular shedding of skin cells, and abnormal invasion of inflammatory mediators. The treatment strategy is designed based on the severity of the disease condition starting from topical, phototherapy, systemic, and biologics. In recent years, extensive research into the underlying mechanisms of psoriasis has led to significant advancement in treatment options from small molecules to biologics. AREA COVERED: This review focuses on intracellular and molecular mechanisms such as AhR, A3AR, RIP1, CGRP, and S1P that serve as novel pharmacological targets for psoriasis. Moreover, new molecules are approved or are under clinical investigation to interfere with these target mechanisms. EXPERT OPINION: A detailed understanding of signaling pathways provides potential targets and molecular mechanisms for the inflammatory cascade in psoriasis. This has led to the development of small molecules targeting specific pathways. Further, the combination of nanotechnology can assist in dose reduction leading to reduced adverse effects in the management of psoriasis.

Evolving Trends in Nanofibers for Topical Delivery of Therapeutics in Skin Disorders.

Nanotechnology has yielded nanostructure-based drug delivery approaches, among which nanofibers have been explored and researched for the potential topical delivery of therapeutics. Nanofibers are filaments or thread-like structures in the nanometer size range that are fabricated using various polymers, such as natural or synthetic polymers or their combination. The size or diameter of the nanofibers depends upon the polymers, the techniques of preparation, and the design specification. The four major processing techniques, phase separation, self-assembly, template synthesis, and electrospinning, are most commonly used for the fabrication of nanofibers. Nanofibers have a unique structure that needs a multimethod approach to study their morphology and characterization parameters. They are gaining attention as drug delivery carriers, and the substantially vast surface area of the skin makes it a potentially promising strategy for topical drug products for various skin disorders such as psoriasis, skin cancers, skin wounds, bacterial and fungal infections, etc. However, the large-scale production of nanofibers with desired properties remains challenging, as the widely used electrospinning processes have certain limitations, such as poor yield, use of high voltage, and difficulty in achieving in situ nanofiber deposition on various substrates. This review highlights the insights into fabrication strategies, applications, recent clinical trials, and patents of nanofibers for different skin disorders in detail. Additionally, it discusses case studies of its effective utilization in the treatment of various skin disorders for a better understanding for readers.

Apremilast loaded lyotropic liquid crystalline nanoparticles embedded hydrogel for improved permeation and skin retention: An effective approach for psoriasis treatment.

The present work aimed to prepare and evaluate Apremilast loaded lyotropic liquid crystalline nanoparticles (LCNPs) formulation for skin delivery to enhance the efficacy with reduced adverse effects of the oral therapy in psoriasis treatment. The LCNPs were prepared using the emulsification using a high shear homogenizer for size reduction and optimized with Box Behnken design to achieve desired particle size and entrapment efficiency. The selected LCNPs formulation was evaluated for in-vitro release, in-vitro psoriasis efficacy, skin retention, dermatokinetic, in-vivo skin retention, and skin irritation study. The selected formulation exhibited 173.25 ± 2.192 nm (polydispersity 0.273 ± 0.008) particle size and 75.028 ± 0.235% entrapment efficiency. The in-vitro drug release showed the prolonged-release for 18 h. The ex-vivo studies revealed that LCNPs formulation exhibited drug retention up to 3.2 and 11.9-fold higher, in stratum corneum and viable epidermis compared to conventional gel preparation. In-vitro cell line studies performed on immortal keratinocyte cells (HaCaT cells) demonstrated non-toxicity of selected excipients used in designed LCNPs. The dermatokinetic study revealed the AUC0-24 of the LCNPs loaded gel was 8.4 fold higher in epidermis and 2.06 fold in dermis, respectively compared to plain gel. Further, in-vivo animal studies showed enhanced skin permeation and retention of Apremilast compared to conventional gel.

Enhanced skin drug delivery using dissolving microneedles: a potential approach for the management of skin disorders.

INTRODUCTION: For decades, finding effective long-term or disease-modifying treatments for skin disorders has been a major focus of scientists. The conventional drug delivery systems showed poor efficacy with high doses and are associated with side effects, which lead to challenges in adherence to therapy. Therefore, to overcome the limitations of conventional drug delivery systems, drug delivery research has focused on topical, transdermal, and intradermal drug delivery systems. Among all, the dissolving microneedles have gained attention with a new range of advantages of drug delivery in skin disorders such as breaching skin barriers with minimal discomfort and its simplicity of application to the skin, which allows patients to administer it themselves. AREAS COVERED: This review highlighted the insights into dissolving microneedles for different skin disorders in detail. Additionally, it also provides evidence for its effective utilization in the treatment of various skin disorders. The clinical trial status and patents for dissolving microneedles for the management of skin disorders are also covered. EXPERT OPINION: The current review on dissolving microneedles for skin drug delivery is accentuating the breakthroughs achieved so far in the management of skin disorders. The output of the discussed case studies anticipated that dissolving microneedles can be a novel drug delivery strategy for the long-term treatment of skin disorders.

Insight into the pivotal role of signaling pathways in psoriasis pathogenesis, potential therapeutic molecules and drug delivery approaches.

Psoriasis is a multifactorial chronic autoimmune skin disorder, the exact cause of which is still under investigation. It is classified into different types displaying various histopathological features such as hyperproliferation, irregular parakeratosis and vascular infiltration of various immune cells with neutrophils in the epidermis. Over the past few decades, psoriasis pathogenesis has been thoroughly researched, leading to several advances in the treatment using small molecules and biologics. This review focuses on describing the role of various signaling pathways, including PDE-4, JAK-STAT, S1P, A3AR and NF-κB, in psoriasis pathogenesis and associated new molecules that are either recently approved or under clinical trials. This study has also addressed the relevance of employing nanotherapeutics to boost the efficacy of psoriasis treatment.