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Clinical Photographs of Chronic Plaque Psoriasis Treated With Topical Liposomal Cyclosporine Nano-Gel
Source publication
Importance:
Attempts to use topical cyclosporine in treatment of psoriasis have failed because of unfavorable physicochemical properties and inappropriate formulation design of the conventional dosage forms.
Objective:
To evaluate the efficacy of topical cyclosporine using liposomal nanocarriers (lipogel) in limited chronic plaque psoriasis.
De...
Contexts in source publication
Context 1
... complete lesion clearance (ie, DSS and PGA scores ≤1) was observed in 23 (60%) of the 38 cyclosporine lipogel-treated lesions after the eighth week , with an 83% reduction in DSS from baseline. At the end of 14th week, 34 (90%) of the sites treated with cyclosporine lipogel showed more than 90% lesion clearance (Figure 3). The placebo-treated sites, how- ever, did not show significant lesion clearance ( Figure 4A). ...
Context 2
... 10% to 20% reduction in DSS in the le- sions treated with placebo lipogel was observed at the sec- ond week onward until the end of the study period, attribut- able to the unique skin hydration and emollient effect of PLs, the major constituent of liposomes present in the placebo lipogel ( Figure 3B). 20 In study arm 2, all lesions treated with cyclosporine lipogel, 2.0%, showed significant fall in DSS after the second week (Wilcoxon signed rank test; P = .02). ...
Citations
... Thin film hydration method Enhance therapeutic efficacy of liposomal than conventional cream at an equal drug concentration [181] Psoralen Thin film hydration method Reduction in the levels of tumor necrosis factor-α, IL-17, and IL-22 Spontaneous emulsification method Prolonged release of drug as predicted by Korsmeyer-Peppas model [190] Methotrexate Emulsification technique Enhanced skin permeation and preservation of drug in profound skin with superior In vivo anti-psoriatic efficacy than plain methotrexate solution [191] Curcumin Low-energy emulsification method 4.87 time rise in permeation of curcumin from the system with quicker healing in psoriatic mice as compared to plain curcumin [192] 6 ...
Psoriasis is a chronic autoimmune disorder that has a major effect on the quality of life for millions of people throughout the world. The pathogenesis of psoriasis has revealed intricate molecular networks and signaling pathways, opening new avenues for precision medicine. Psoriasis treatments include topical therapy, phototherapy, systemic therapies, and biologics, but achieving optimal outcomes is difficult. Despite advancements in understanding the causes of psoriasis and the development of various treatments, optimizing therapeutic outcomes remains challenging. Managing psoriasis poses challenges in terms of drug delivery and evaluation models. Novel drug delivery systems capable of navigating complex skin barriers and delivering therapeutics precisely to target cells are crucial for advancing treatment options. This article provides an inclusive overview of psoriasis, highlighting recent discoveries and potential therapeutic targets. The article emphasizes the importance of combining different modalities, such as synthetic and herbal agents, with biologics to improve efficacy. Nanocarriers show promise for targeted drug delivery in psoriasis, as they can encapsulate antipsoriatic drugs, biologics, and gene therapies, providing enhanced stability, improved tissue penetration, and precise cellular targeting. These advancements in drug delivery systems have the potential to revolutionize psoriasis treatment by maximizing efficacy while minimizing side effects. The article also discusses the commercial outcomes in psoriasis formulations, including patents related to treatment and ongoing clinical trials, which provide valuable insights into the evolving landscape of psoriasis therapeutics. These insights contribute to the evolving field of psoriasis therapeutics and offer hope for improved outcomes for patients suffering from psoriasis.
... This activates T lymphocytes, which then multiply and enter the bloodstream. They reach the site of inflammation through a process called extravasation, similar to that seen in leukocytes [23,24]. ...
... For example, the cost of alleviating physical and psychological symptoms for US residents is approximately $11,498 per person. Psoriasis patients also experience psychological, emotional, and financial stress, with depression being a common comorbidity [24][25][26][27][28]. Nail psoriasis can cause both physical and emotional pain and requires prompt and effective treatment. ...
Psoriasis is a complex autoimmune skin condition with a significant genetic component. It causes skin inflammation and is characterized by flaky, silvery reddish spots that can worsen with age. This condition results from an impaired immunological response of T-cells and affects 2-5% of the global population. The severity of the illness determines the choice of treatment. Topical treatments are commonly used to treat psoriasis, but they can have several adverse effects. Biological therapy is another option for treating specific types of psoriasis. Recently, new nanoformulations have revolutionized psoriasis treatment. Various nanocarriers, such as liposomes, nanostructured lipid nanoparticles, niosomes, and nanoemulsions, have been developed and improved for drug delivery. The use of nanocarriers enhances patient compliance, precise drug delivery, and drug safety. This review aims to suggest new nanocarrier-based drug delivery systems for treating psoriasis. It discusses the importance of nanocarriers and compares them to traditional treatments. Anti-psoriatic drugs have also been investigated for cutaneous delivery using nanocarriers. The review also covers various factors that influence dermal targeting. By highlighting several relevant aspects of psoriasis treatment, the review emphasizes the current potential of nanotechnology. Using nanocarriers as a drug delivery technique may be a promising alternative treatment for psoriasis.
... Some of the obstacles connect-ed with using nanotechnology in clinical therapies have been identified through studies on nanotechnology's ability to inhibit nanocarrier interaction with biological systems. A new treatment method could be introduced to the market to help meet a variety of biological and medicinal needs [136] besides these challenges. Drug therapeutic effect enhancement, improved pharmacokinetics and pharmacodynamic profile, sustained and controlled release profile of the bioactive, sitespecific delivery, improved drug absorption and reduced side Fig. (1). ...
Psoriasis is an inflammatory and proliferative autoimmune dermatological disorder. It is a skin ailment that is defined by particular, drab-red or peach-pink stiff areas with silvery scales patches. Other typical characteristics include the proliferation of epidermal layer, aberrant keratinization, hyperkeratosis, increased micro capillary vascularization, and infiltration of inflammatory mediator loaded cells. Conventional pharmacotherapies currently available can only provide minor advantages. Nanomedicines based on nanotechnology can potentially improve the efficacy and safety of psoriasis medications. Apoptosis plays an important pathogenetic role in many chronic inflammatory diseases, including those of dermatological interest, in particular, regarding psoriasis. In this regard, treatments with antioxidant properties could be appropriate therapeutic options. We reviewed the available studies on the efficacy of antiapoptotic therapies in psoriasis. We'll look at phytochemicals in this review, which are natural components found in plants with antiapoptotic activity that are frequently used to treat psoriasis. For improved topical treatment, we also take into consideration the advantages of loading phytoconstituents as medicines into lipid based nanocarriers. The utilization of herbal nanomedicines in psoriasis, as well as nano delivery carrier system for phytoconstituents with improved therapeutic profiles and decreased toxicity, are the subjects of this review. The study's purpose is to find more effective herbal nanomedicines for treating psoriasis. In the treatment of psoriasis, phytoconstituents that have shown antipsoriatic potential in recent years, as well as phytoconstituents loaded based nanomedicines, have a lot of promising roles to be explored. Furthermore, very few patents have been found in the field of nanotechnology utilizing lipid-based nanocarrier system for the treatment of psoriasis. Therefore, this review greatly compels the researcher to validate the process development of lipid-based drug delivery system for the patentability of the product. This should be in a view of shifting in the applicability of the drug delivery system for general public health as a potential treatment option in psoriasis.
... The reduced sizes are associated with specific features such as increased saturation solubility, increased dissolution velocity, increased cutaneous adhesion and increased drug cutaneous permeation. However, some authors obtained nanostructures with mean diameters higher than 900 nm (Abdelbary and Aboughaly 2015;Kumar et al. 2016). In those cases, the formulations deliver their contents into the superficial layers of skin remaining within the stratum corneum (Abdelbary and Aboughaly, 2015). ...
... A randomized clinical trial was conducted to evaluate CYA lipogel (Kumar et al., 2016). The double-blinded single-center randomized clinical trial (n = 38) was conducted using a three-arm parallel-group and compared once-a-day application of CYA lipogel 2.0 % with placebo lipogel, CYA o/w 0.2 % cream or clobetasol propionate cream. ...
... Ethanol injection method Mean diameter of 111 nm, zeta potential of + 41 mV, and drug entrapment of 93 %. (Walunj et al., 2020) CYA Liposomes Standard thin-film technique Mean diameter of 950 nm and drug entrapment of 97 %. (Kumar et al., 2016) CYA Niosomes Thin-film hydration method ...
Psoriasis is a recurring, immune-mediated dermatological disorder. Many therapeutic agents are available for the treatment of psoriasis, including immunosuppressants and biologic treatments with immunosuppressant action. The employment of nanotechnology allows drug tailoring to achieve dermal targeting, improve efficacy and minimize undesirable effects. Here we discuss the use of the topical route in combination with nano-based drug delivery systems containing immunosuppressants for the management of psoriasis. This review is based on articles selected from 2011 to 2022, using the keywords "Psoriasis" AND "Immunosuppressants" AND "Nano*" in the main databases. Fifty-seven articles were retrieved, although only forty-two matched the inclusion criteria. Nanocarriers such as liposomes, ethosomes, niosomes, solid lipid nanoparticle, nanostructured lipid carriers and microspheres containing immunosuppressive drugs (methotrexate, cyclosporine, tacrolimus, and etanercept) were identified. The main findings of these studies are related to the improved in vitro/ex vivo permeation/penetration and therapeutic efficacy of nanoparticles in vitro and in vivo, compared to the drug in solution. Based on the studies discussed in this review, encapsulation in several types of nanocarriers decreases toxicity, dose, and dose frequency. Furthermore, it enables specific targeting of the active drug, pointing to the possibility of improving topical therapy for psoriasis. In conclusion, nanoformulations represent a novel and promising tool for psoriasis treatment.
... However, more adverse effects such as dysphagia, dyspepsia, burning sensation, lips swelling, gastrointestinal upset were reported as the side effect of mouthwash Cyc-A, 25,27,29 and topical application of Cyc-A lipogel on the skin resulted in cases of mild erythema, dryness, and fissuring. 32 Regarding the treatment of pyoderma gangrenosum, Azizan et al. ...
... After a month of treatment with mouthwash, results were reported as follows: marked improvement in five, moderate response in six, a slight improvement in three patients, and no changes only in one patient. VAS reduction, from score 8.7 to 3.5, were significant and Cyc-A mouthwash appeared to be a beneficial treatment in patients with burning mouth syndrome.3.2.4 | Plaque psoriasisKumar et al.,32 designed a double blinded RCT to evaluate the efficacy of the topical Cyc-A lipogel 2% in the treatment of mild-to-moderate stable plaque psoriasis. A total number of 38 patients were enrolled in the study. ...
... Several studies on the topical application of Cyc-A in varying dosage regimens (0.1%-10%, wt/wt) with different topical carriers, have failed to yield the expected clinical response, likely due to poor absorption. The poor cutaneous absorption was attributed to the unfavorable physicochemical properties, such as low aqueous solubility, high molecular weight, and high lipophilicity.32,36 Multiple ongoing studies focus on increasing the skin permeability of Cyc-A.However, animal studies, have shown a topical formulation of Cyc-A nano-capsules (NCs) can enhanced drug penetration into the different layers of the porcine ear skin.11 ...
... However, more adverse effects such as dysphagia, dyspepsia, burning sensation, lips swelling, gastrointestinal upset were reported as the side effect of mouthwash Cyc-A, 25,27,29 and topical application of Cyc-A lipogel on the skin resulted in cases of mild erythema, dryness, and fissuring. 32 Regarding the treatment of pyoderma gangrenosum, Azizan et al. ...
... After a month of treatment with mouthwash, results were reported as follows: marked improvement in five, moderate response in six, a slight improvement in three patients, and no changes only in one patient. VAS reduction, from score 8.7 to 3.5, were significant and Cyc-A mouthwash appeared to be a beneficial treatment in patients with burning mouth syndrome.3.2.4 | Plaque psoriasisKumar et al.,32 designed a double blinded RCT to evaluate the efficacy of the topical Cyc-A lipogel 2% in the treatment of mild-to-moderate stable plaque psoriasis. A total number of 38 patients were enrolled in the study. ...
... Several studies on the topical application of Cyc-A in varying dosage regimens (0.1%-10%, wt/wt) with different topical carriers, have failed to yield the expected clinical response, likely due to poor absorption. The poor cutaneous absorption was attributed to the unfavorable physicochemical properties, such as low aqueous solubility, high molecular weight, and high lipophilicity.32,36 Multiple ongoing studies focus on increasing the skin permeability of Cyc-A.However, animal studies, have shown a topical formulation of Cyc-A nano-capsules (NCs) can enhanced drug penetration into the different layers of the porcine ear skin.11 ...
Cyclosporine‐A (Cyc‐A) was initially prescribed as systemic therapy for patients receiving solid organ transplants or in patients with graft versus host disease (GVHD). Topical Cyc‐A is an ideal form of Cyclosporine in the treatment of mucocutaneous disorders as it causes fewer systemic side effects and has more stable results than steroids; however, poor absorption through the skin makes the development of new formulations necessary to improve skin permeability. To evaluate the efficacy and safety of topical Cyc‐A in different dermatological conditions. A thorough systematic review was performed on PubMed/Medline, Embase, Scopus, and Web of Science databases as well as Google Scholar, and relevant studies from 2000 until January 3rd, 2022, were selected. The study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta‐Analysis (PRISMA). Topical Cyc‐A was observed to be an effective medication in the treatment of oral lichen planus, psoriasis, burning mouth syndrome, Pyoderma Gangrenosum, and Zoon's balanitis. Adverse side effects such as dysphagia, burning sensation, lips swealing, and gastrointestinal upset were reported following Cyc‐A mouthwash use, whereas mild erythema, dryness, and fissuring of the skin were observed following the Cyc‐A lipogel application. Topical Cyc‐A was found to be a good alternative to traditional treatment regimens for immune‐mediated mucocutaneous conditions. Cyc‐A can be considered as a safe and efficient option in cases of long‐term treatment as it does not have the same adverse effects of long‐term steroids. This article is protected by copyright. All rights reserved.
... (sodium 10-amino-2-methoxyundecanoate) (Kumar et al. 2016). Figure 6 depicts several types of nanoparticles (NPs). ...
Chronic diseases, as stated by the WHO, are a threat to human health which kill 3 out of every 5 people worldwide. Therapeutics for such illnesses can be developed using traditional medicine. However, it is not an easy path from natural products to Western pharmacological and pharmaceutical methods. For several decades, chronic inflammatory disorders, especially in Westernized countries, have increased incidence and prevalence. Several NSAIDs are used to decrease inflammation and pain; however, there are numerous negative consequences of these anti-inflammatory medications, whereas plant-based natural products have anti-inflammatory therapeutic benefits that have little or no adverse effects. Nanoparticles are a new type of drug delivery device that may be designed to provide excellent target selectivity for certain cells and tissues while also having a high drug loading capacity, resulting in better pharmacokinetics, pharmacodynamics (PKPD), and therapeutic bioavailability. The size and polarity of phytochemical compounds make it hard to pass the blood–brain barrier (BBB), blood-vessel endothelial lining, gastrointestinal tract and mucosa. In addition, the gastrointestinal system is enzymatically destroyed. Therefore, nanoparticles or nanocrystals might also be used for encapsulation or conjugation of these chemicals as a method to improve their organic effectiveness through their gastrointestinal stability, absorption rate and dispersion. The therapy of numerous inflammatory illnesses, including arthritis, gastritis, Nephritis, Hepatitis (Type A, B &C), ulcerative colitis, Alzheimer's disease, atherosclerosis, allergic responses (asthma, eczema) or autoimmune disorders, is characterised by nanoparticles. This review paper provides information on the numerous nanosystem described with their probable mechanism to treat chronic inflammatory diseases.
... Different approaches have been tried to solubilize CyA with different nanolipid carriers (NLCs) in solution and gel form using lipids/amphiphilic gels/polymer with ionic/non-ionic surfactant with the possibility of delivering CyA into and through the different layers of skin [22]. According to clinical data published by Kumar et al. [23] and a clinical review by Kim et al. [24] authors recommended topical treatment of cyclosporine for mild to moderate psoriasis. In 80% of patients with mild-to-moderate psoriasis, the topical treatment is recommended [25,26]. ...
Psoriasis is an autoimmune, chronic proliferative, inflammatory skin disease with high comorbidity. Psoriasis is not a curable disease; it can only be managed. Cyclosporine A (CyA) is one of the FDA-approved immunosuppressant drug used in severe Psoriasis. Till date only oral route is used for its administration. Administration of CyA by this route causes serious side effects such as hypertension and renal toxicity. Due to these side effects, a number of researches have been done and taking place in the current times for the dermal delivery of CyA for the management of psoriasis. Dermal delivery of CyA is not an easy task because of its physiochemical properties like high molecular weight, lipophilicity and resistance offered by stratum corneum (SC). Because of the above problems in the dermal delivery a number of new approaches such as nanolipid carriers, microemulsion, liposomes, niosomes etc. are explored. To those deep findings for psoriasis management with dermal delivery of CyA have not been discussed. This comprehensive review includes all the studies, advancements and their critical findings which took place in the recent times for the dermal delivery of CyA and along with the suitable modification needed for the efficient dermal delivery of CyA are also suggested.Graphic abstract
... As an immunosuppressant that is administered orally or via injection, cyclosporine is used to treat nephrotic syndrome (Cattran et al., 2007), psoriasis (Kumar et al., 2016), and keratoconjunctivitis sicca (dry eyes; Kasper et al., 2017). Four KS domains were also identified: naphthopyrone (KS4 on contig 12), avermectin (KS1 on contig 17), myxothiazol (KS2 on contig 17), and epothilone (KS3 on contig 17). ...
Yuanmo [Sarcomyxa edulis (Y.C. Dai, Niemelä & G.F. Qin) T. Saito, Tonouchi & T. Harada] is an important edible and medicinal mushroom endemic to Northeastern China. Here we report the de novo sequencing and assembly of the S. edulis genome using single-molecule real-time sequencing technology. The whole genome was approximately 35.65 Mb, with a G + C content of 48.31%. Genome assembly generated 41 contigs with an N50 length of 1,772,559 bp. The genome comprised 9,364 annotated protein-coding genes, many of which encoded enzymes involved in the modification, biosynthesis, and degradation of glycoconjugates and carbohydrates or enzymes predicted to be involved in the biosynthesis of secondary metabolites such as terpene, type I polyketide, siderophore, and fatty acids, which are responsible for the pharmacodynamic activities of S. edulis. We also identified genes encoding 1,3-β-glucan synthase and endo-1,3(4)-β-glucanase, which are involved in polysaccharide and uridine diphosphate glucose biosynthesis. Phylogenetic and comparative analyses of Basidiomycota fungi based on a single-copy orthologous protein indicated that the Sarcomyxa genus is an independent group that evolved from the Pleurotaceae family. The annotated whole-genome sequence of S. edulis can serve as a reference for investigations of bioactive compounds with medicinal value and the development and commercial production of superior S. edulis varieties.
... Here, adapting the liposome size, adapting the zeta potential, and increasing the membrane flexibility to further permeate the skin resulted in an increased efficacy of topical cyclosporine [123]. The application of topical cyclosporine was also evaluated clinically, where treatment with cyclosporine lipogel resulted in complete clearance in 41% of psoriasis lesional sites in a safe manner [124]. Even though liposomal formulations often result in an improved efficacy of the encapsulated drug, other formulations may be more suited, as was revealed in a clinical study where anthralin was loaded into a liposomal and ethosomal gel. ...
... Finally, the required route of administration of these products can form another hurdle, as nonliposomal counterparts of liposomal drug products are often available in a pill, while liposomal drug products often require I.V. administration, which may deter end users (clinicians and patients) in adopting such new therapies. Despite these significant challenges, several clinical trials have been conducted where liposomal drug formulations have been positively evaluated for treatment of inflammatory disease, such as rheumatoid arthritis, psoriasis, atherosclerosis, and transplantation [124,166,188,203], but not all trials result in progression to publication and/or the clinic [203]. ...
Liposomes can be seen as ideal carriers for anti-inflammatory drugs as their ability to (passively) target sites of inflammation and release their content to inflammatory target cells enables them to increase local efficacy with only limited systemic exposure and adverse effects. Nonetheless, few liposomal formulations seem to reach the clinic. The current review provides an overview of the more recent innovations in liposomal treatment of rheumatoid arthritis, psoriasis, vascular inflammation, and transplantation. Cutting edge developments include the liposomal delivery of gene and RNA therapeutics and the use of hybrid systems where several liposomal bilayer features, or several drugs, are combined in a single formulation. The majority of the articles reviewed here focus on preclinical animal studies where proof-of-principle of an improved efficacy-safety ratio is observed when using liposomal formulations. A few clinical studies are included as well, which brings us to a discussion about the challenges of clinical translation of liposomal nanomedicines in the field of inflammatory diseases.
