Emerging trends in combination strategies with phototherapy in advanced psoriasis management.

Psoriasis is a non-contagious, chronic, relapsing inflammatory skin disease with cutaneous manifestations such as red, raised scaly plaques. Current treatment approaches for psoriasis comprise topical therapy, systemic therapy, phototherapy, psoralen with UVA(PUVA) and biologics. Regardless of the progression in therapeutic approaches (novel therapies like biologics) in psoriasis, phototherapy is also an economical, compelling and safe treatment option that lacks the immunosuppressive properties as well as the toxicities of traditional modalities. It can be combined safely with other therapeutic options such as topical therapies and novel biologics and provide effective therapy. The aim of the current review is to analyze the literature on the safety as well as the efficacy of phototherapy with various treatment modalities in the management of psoriasis. This review summarizes randomized controlled clinical trials addressing combinations of phototherapy with other treatment modalities for the management of psoriasis. The findings of these clinical studies are elaborated.

Bridging the gap: academia, industry and FDA convergence for nanomaterials.

Nano-medicine is the fastest growing field in pharmaceutical industry today. However, there still exist several hurdles preceding its clinical translation. This review provides insights on the guidelines for nanomaterials provided by the US-FDA (United States Food and Drug Administration), various approval pathways and also addresses the lacunae between academic research, pharmaceutical industry and US-FDA through an attempt to overcome the hurdle to its clinical translation. We have also emphasized various ways to overcome the described barriers which will provide the readers a brief understanding over the critical aspects where the scope of the guidelines may need to be revisited in order to exhibit their successful clinical translation from academic research to commercial feasibility.

High mobility group box 1 cytokine targeted topical delivery of resveratrol embedded nanoemulgel for the management of atopic dermatitis.

Resveratrol is a polyphenolic compound showing anti-inflammatory activity by inhibition of high mobility group box 1 cytokine responsible for the activation of nuclear factor-κB pathway in atopic dermatitis. To evaluate the efficacy of resveratrol through topical route we have developed resveratrol-loaded nanoemulgel for the effective management of atopic dermatitis in mice model. The resveratrol-loaded nanoemulsion (0.5%, 0.75% and 1% w/w) was optimized by spontaneous nano-emulsification. The optimized resveratrol-loaded nanoemulsions showed average globule size in the 180-230 nm range and found to be monodispersed. The resveratrol nanoemulgel was prepared with a SEPINEO™ P 600 gel base and propylene glycol. Ex vivo permeation and retention study resulted in significantly higher skin retention of resveratrol from resveratrol-loaded nanoemulgel than free resveratrol-loaded gel. Preclinical efficacy of resveratrol nanoemulgel displayed promising therapeutic outcomes where, western blotting of skin tissues disclosed a significant reduction in the relative expression of high mobility group box 1, the receptor for advanced glycation end products, toll-like receptor-4 and phosphorylated nuclear factor-κB. Further, real-time polymerase chain reaction also disclosed a significant reduction in pro-inflammatory cytokines such as thymic stromal lymphopoietin, interleukin-4, interleukin-13, interleukin-31, tumor necrosis factor-α and interleukin-6. The histopathological examination of skin sections showed improvement in the skin condition. Collectively, the findings from our study showcased the significant improvement in the atopic dermatitis skin condition in mice model after topical application of resveratrol loaded nanoemulgel.

Exploration of novel drug delivery systems in topical management of osteoarthritis.

Osteoarthritis is one of the foremost disabling disorders in the world. There is no definitive treatment to prevent the progression of osteoarthritis. Hence, palliative treatment aims at minimizing pain, disability and improving function, performance and quality of life. Oral administration of nonsteroidal anti-inflammatory drug is associated with number of adverse effects and reduced therapeutic efficacy. Intra-articular injection has been the preferred route of drug administration. However, the clearance of drug from the arthritic site, risk of infections, cost and the pain associated with frequent injections make this route highly non-compliant to patients. Since osteoarthritis is a chronic condition which requires treatment for prolonged duration, there is an urgent need for another administration route which circumvents the hindrances linked with intra-articular route. Transdermal route across the skin locally at the osteoarthritis site could help in surpassing the disadvantages associated with intra-articular route. However, traversing skin barrier and reaching the chondrocytes with sufficient amount of the drug is extremely difficult. Nanocarrier-based approaches could hold an answer to the said shortcomings owing to their reduced size, targeting tunability and site specificity. In this article, we discuss the pathophysiology of osteoarthritis, molecular targets, and utilization of nanocarrier-based approaches to strategize the treatment of osteoarthritis in a new direction, i.e. topical delivery of nanocarriers in osteoarthritis.

Forging Ahead the Repositioning of Multitargeted Drug Ivermectin.

With the advent of ivermectin, tremendous improvement in public health has been observed, especially in the treatment of onchocerciasis and lymphatic filariasis that created chaos mostly in rural, sub-Saharan Africa and Latin American countries. The discovery of ivermectin became a boon to millions of people that had suffered in the pandemic and still holds its pharmacological potential. Ivermectin continued to surprise scientists because of its notable role in the treatment of various other tropical diseases (Chagas, leishmaniasis, worm infections, etc.) and is viewed as the safest drug with the least toxic effects. The current review highlights its role in unexplored avenues towards forging ahead of the repositioning of this multitargeted drug in cancer, viral (the evaluation of the efficacy of ivermectin against SARS-Cov-2 is under investigation) and bacterial infection and malaria. This article also provides a glimpse of regulatory considerations of drug repurposing and current formulation strategies. Due to its broad-spectrum activity, multitargeted nature and promising efforts are put towards the repurposing of this drug throughout the field of medicine. This single drug originated from a microbe, changed the face of global health by proving its unmatched success and progressive efforts continue in maintaining its bequestnin the management of global health by decreasing the burden of various diseases worldwide.

Emerging insights of peptide-based nanotherapeutics for effective management of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, prevalent, immune-mediated, inflammatory, joint disorder affecting millions of people worldwide. Despite current treatment options, many patients remain unable to achieve remission and suffer from comorbidities. Because of several comorbidities as well as its chronic nature, it diminishes the quality of patients' life and intensifies socioeconomic cargo. Consolidating peptides with immensely effective drug delivery systems has the ability to alleviate adverse effects associated with conventional treatments. Peptides are widely used as targeting moieties for the delivery of nanotherapeutics. The use of novel peptide-based nanotherapeutics may open up new avenues for improving efficacy by promoting drug accumulation in inflamed joints and reducing off-target cytotoxicity. Peptide therapeutics have grabbed significant attention due to their advantages over small drug molecules as well as complex targeting moieties. In light of this, the market for peptide-based medications is growing exponentially. Peptides can provide the versatility required for the successful delivery of drugs due to their structural diversity and their capability to lead drugs at the site of inflammation while maintaining optimum therapeutic efficacy. This comprehensive review aims to provide an enhanced understanding of recent advancements in the arena of peptide-based nanotherapeutics to strengthen targeted delivery for the effective management of rheumatoid arthritis. Additionally, various peptides having therapeutic roles in rheumatoid arthritis are summarized along with regulatory considerations for peptides.

Perspective insights of small molecules, phytoconstituents and biologics in the management of psoriasis: A focus on targeting major inflammatory cytokine pathways.

Psoriasis is an enduring, pruritic and papulosquamous skin ailment that poses a significant burden on public health. It is mainly characterized by hyperkeratosis, acanthosis, parakeratosis, scaly and erythematous plaques. Biomarkers like interleukin-17, interleukin-12 and -23 and tumor necrosis factor-α serve as key drivers of psoriatic pathogenesis. Triggered release of pro-inflammatory cytokines from various up-regulated pathways leads to psoriatic inflammation. Several target moieties like biologics, small molecules and herbal moieties play a fundamental role in the repression of pathogenesis of psoriasis. Biologics and small molecules engaged in the management of psoriasis have been emphasized in detail. An insight into nano-carrier interventions on herbal moieties and clinical aspects of psoriasis are also highlighted. This review emphasizes various pathological targets involved in psoriasis.

Old drugs, new tricks: Emerging role of drug repurposing in the management of atopic dermatitis.

Atopic dermatitis is a chronic recurring pruritic inflammatory skin disease manifested by increased pro-inflammatory mediators which lead to dry, thickened, cracked, scaly skin. The current treatment options for atopic dermatitis management comprise drawbacks and leave unmet effective clinical needs. So, the approach for repurposing existing drugs for atopic dermatitis management may potentially overcome these unmet needs. Diseases that share the common pathophysiological pathways with atopic dermatitis can serve as a foundation for the repurposing of drugs. Drugs used in the management of cancer, rheumatoid arthritis, and other immune-mediated diseases such as psoriasis are under investigation to know the potential in atopic dermatitis management by utilizing repurposing strategies for a novel therapeutic indication. This review mainly envisages the probable repurposing of drugs for the management of atopic dermatitis disease; the barriers and regulatory aspects involved in the repurposing of existing drugs.

Polymer nanotherapeutics: A versatile platform for effective rheumatoid arthritis therapy.

Rheumatoid arthritis is an aggressive and severely debilitating disorder that is characterized by joint pain and cartilage damage. It restricts mobility in patients, leaving them unable to carry out simple tasks. RA presents itself with severe lasting pain, swelling and stiffness in the joints and may cause permanent disability in patients. Treatment regimens currently employed for rheumatoid arthritis revolve around keeping clinical symptoms like joint pain, inflammation, swelling and stiffness at bay. The current therapeutic interventions in rheumatoid arthritis involve the use of non-steroidal anti-inflammatory drugs, glucocorticoids, disease-modifying anti-rheumatic drugs and newer biological drugs that are engineered for inhibiting the expression of pro-inflammatory mediators. These conventional drugs are plagued with severe adverse effects because of their higher systemic distribution, lack of specificity and higher doses. Oral, intra-articular, and intravenous routes are routinely used for drug delivery which is associated with decreased patient compliance, high cost, poor bioavailability and rapid systemic clearance. All these drawbacks have enticed researchers to create novel strategies for drug delivery, the main approach being nanocarrier-based systems. In this article, we aim to consolidate the remarkable contributions of polymeric carrier systems including microneedle technology and smart trigger-responsive polymeric carriers in the management of rheumatoid arthritis along with its detailed pathophysiology. This review also briefly describes the safety and regulatory aspects of polymer therapeutics.

Gauging the role and impact of drug interactions and repurposing in neurodegenerative disorders.

Neurodegenerative diseases (ND) are of vast origin which are characterized by gradual progressive loss of neurons in the brain region. ND can be classified according to the clinical symptoms present (e.g. Cognitive decline, hyperkinetic, and hypokinetic movements disorder) or by the pathological protein deposited (e.g., Amyloid, tau, Alpha-synuclein, TDP-43). Alzheimer's disease preceded by Parkinson's is the most prevalent form of ND world-wide. Multiple factors like aging, genetic mutations, environmental factors, gut microbiota, blood-brain barrier microvascular complication, etc. may increase the predisposition towards ND. Genetic mutation is a major contributor in increasing the susceptibility towards ND, the concept of one disease-one gene is obsolete and now multiple genes are considered to be involved in causing one particular disease. Also, the involvement of multiple pathological mechanisms like oxidative stress, neuroinflammation, mitochondrial dysfunction, etc. contributes to the complexity and makes them difficult to be treated by traditional mono-targeted ligands. In this aspect, the Poly-pharmacological drug approach which targets multiple pathological pathways at the same time provides the best way to treat such complex networked CNS diseases. In this review, we have provided an overview of ND and their pathological origin, along with a brief description of various genes associated with multiple diseases like Alzheimer's, Parkinson's, Multiple sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Huntington's and a comprehensive detail about the Poly-pharmacology approach (MTDLs and Fixed-dose combinations) along with their merits over the traditional single-targeted drug is provided. This review also provides insights into current repurposing strategies along with its regulatory considerations.