Effective Treatment For Psoriasis Research Articles

Oral and Topical Vitamin D, Sunshine, and UVB Phototherapy Safely Control Psoriasis in Patients with Normal Pretreatment Serum 25-Hydroxyvitamin D Concentrations: A Literature Review and Discussion of Health Implications.

Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s, interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/mL). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

Role of Haratala Shodhana in the therapeutic efficacy of Rasamanikya along with Guduchi Ghana in the treatment of Ekakushtha (psoriasis): A double-blind randomised clinical trial.

Rasamanikya (RM) and Guduchi Ghana (GG) are well-known formulations for treating skin disorders in Ayurveda. The drug RM is prepared from Shuddha Haratala (processed orpiment) as a single ingredient. In the present study, RM was prepared from the Haratala, which was Shodhita, with two different media, viz., Kushmanda Swarasa and Churnodaka. In the classics, the preparation of RM is mentioned in the Kushmanda Shodhita Haratala. However, the availability and cost of Kushmanda are the main points of concern in the present era. Shodhana of Haratala by Churnodaka is more cost-effective than Kushmanda Swarasa. The aim of this study is to evaluate the comparative efficacy of RM prepared by Churnodaka Shodhita Haratala (CSHRM) and RM prepared by Kushmanda Shodhita Haratala (KSHRM) with GG in Ekakustha (psoriasis). The study was a randomized double-blind study involving 76 patients with Ekakushtha that were randomly divided into two groups. Patients registered in group A (n = 37) were treated with CSHRM with GG (125 mg + 375 mg) and group B (n = 36) with KSHRM with GG (125 mg + 375 mg) for 8 weeks. The Wilcoxon signed rank test and paired t-test were applied to evaluate the effect of therapy in the individual group for subjective criteria like the PASI score, Matsyashakalopamam (looks like the scales of a fish), Rukshata (dryness), Aswedanam (anhydrosis), Daha (burning), Strava (discharge), Unnati (raised patches), Kandu (itching), Mahavastu (broad-based), and Vaivarnya (discoloration), while the comparison of results between the groups for the same was done by applying the Coefficient of Variation (CV). CSHRM with GG showed better results in all signs and symptoms except Matsyaskalopamam, Aswedanam, Strava, Mahavastu, Nindra and DLQI in terms of the coefficient of variation. In both groups, statistically highly significant (P > 0.001) improvement was found in the signs and symptoms of Ekakushtha. However, the difference between the groups was statistically nonsignificant. Rasamanikya prepared with both media Shodhita Haratala along with Guduchi Ghana was discovered to be a safe and effective psoriasis treatment.

Therapeutic wavelengths of ultraviolet B radiation activate apoptotic, circadian rhythm, redox signalling and key canonical pathways in psoriatic epidermis

Ultraviolet B radiation (UVB) exerts pleiotropic effects on human skin. DNA damage response and repair pathways are activated by UVB; if damage cannot be repaired, apoptosis ensues. Although cumulative UVB exposure predisposes to skin cancer, UVB phototherapy is widely used as an effective treatment for psoriasis. Previous studies defined the therapeutic action spectrum of UVB and showed that psoriasis is resistant to apoptosis. This study aimed to investigate early molecular responses within psoriasis plaques following irradiation with single equi-erythemogenic doses of clinically-effective (311 nm, narrow-band) compared to clinically-ineffective (290 nm) UVB. Forty-eight micro-dissected epidermal samples from 20 psoriatic patients were analyzed using microarrays. Our bioinformatic analysis compared gene expression between 311 nm irradiated, 290 nm irradiated and control psoriasis epidermis to specifically identify 311 nm UVB differentially expressed genes (DEGs) and their upstream regulatory pathways. Key DEGs and pathways were validated by immunohistochemical analysis.There was a dynamic induction and repression of 311 nm UVB DEGs between 6 h and 18 h, only a limited number of DEGs maintained their designated expression status between time-points. Key disease and function pathways included apoptosis, cell death, cell migration and leucocyte chemotaxis. DNA damage response pathways, NRF2-mediated oxidative stress response and P53 signalling were key nodes, interconnecting apoptosis and cell cycle arrest. Interferon signalling, dendritic cell maturation, granulocyte adhesion and atherosclerotic pathways were also differentially regulated. Consistent with these findings, top transcriptional regulators of 311 nm UVB DEGs related to: a) apoptosis, DNA damage response and cell cycle control; b) innate/acquired immune regulation and inflammation; c) hypoxia/redox response and angiogenesis; d) circadian rhythmicity; f) EGR/AP1 signalling and keratinocyte differentiation; and g) mitochondrial biogenesis.This research provides important insights into the molecular targets of 311 nm UVB, underscoring key roles for apoptosis and cell death. These and the other key pathways delineated may be central to the therapeutic effects of 311 nm in psoriasis.

Topical delivery of cyclosporine loaded tailored niosomal nanocarriers for improved skin penetration and deposition in psoriasis: Optimization, ex vivo and animal studies

Psoriasis is a chronic disease treated using topical application of calcineurin inhibitors. However, due to physico-chemical nature of psoriatic stratum corneum, the topical drug delivery is very challenging. The present study aims to explore the potential of niosomes to improve the topical delivery of cyclosporine (penetration and deposition) for effective treatment of psoriasis. The niosomes-gel was prepared by film hydration method using cholesterol, Span 60 and Carbopol 940 (gelling agent). The factorial design (32) was applied to optimize the size (128 nm) and poly dispersibility index (PDI = 0.14) of niosomes by selecting cholesterol: Span 60 ratio at 160 mg: 313.6 mg and hydration time at 42.9 min. In ex vivo permeability studies (rat skin), the niosomes showed high permeation (50.57% in 24 h) in comparison to the cyclosporine suspension (10.13% in 24 h). The drug deposition study showed 59 fold increase in the cyclosporine deposition in the stratum corneum (SC) and the viable epidermis/dermis (VED) layers, which was further ensured by Coumarin 6 fluorescence microscopy. The histopathology and psoriasis area - severity index (PASI) scores in the imiquimod induced psoriatic plaque model showed significant drop in the scoring with niosomes. In conclusion, the optimized niosomes showed promising results to improve the cyclosporine penetration and deposition in the skin tissue for the effective treatment of psoriasis.

Solid lipid nanocarriers embedded hydrogel for topical delivery of apremilast: In-vitro, ex-vivo, dermatopharmacokinetic and anti-psoriatic evaluation

The present work aimed to develop topical solid lipid nanocarriers (SLN) loaded hydrogel of apremilast (API) for psoriasis therapy to minimize the systemic adverse effects. The quality by design approach was implemented for the optimization of API loaded SLN using Box-Behnken design. SLN were prepared using hot emulsification followed by size reduction using probe sonication. The size and entrapment were found to be 167.70 nm ± 1.5 (0.238 PDI) and 63.84 ± 0.93%, respectively. The FESEM images of SLN dispersion portrayed the spherical shape of nanocarriers. The in vitro drug release of SLN dispersion showed extended-release up to 18 h and followed the Korsmeyyar-Peppas model with a regression value of 0.958 (n = 0.330), and Akaike index criteria was 63.69. In vitro cell line study, the MTT assay depicted the formulation excipients had minimal effect, and high internalization was observed with SLN dispersion (1.4-fold). The Ct value reduction in the relative expression of TNF-α miRNA was 3-fold higher with SLN dispersion compared to the positive control. The ex vivo skin retention and dermal distribution study by Coumarin-6 dye depicted an increase in permeation and retention with SLN formulation compared to free drug-loaded gel. The dermato-pharmacokinetic study of SLN formulation exhibited 2-fold higher drug retention in the epidermis and 5-fold higher in the dermis compared to free drug. This were stable for 3 months without significant changes. The results suggest that API loaded SLN can be utilized for topical delivery for effective treatment of psoriasis by targeting skin layers. The API loaded SLN based topical gel formulation showed improved permeation, skin deposition and prolonged release compared to conventional preparation. The designed preparation can signify a potential alternative for psoriasis treatment after clinical evaluation in near future.

ROLE OF PATHYAPATHYA IN THE MANAGEMENT OF EKA KUSHTHA (PSORIASIS)

Ayurveda is not merely a medical science. It is a complete life science. In Ayurveda all skin diseases are described under the Kushtha, which are further divided into Maha Kushtha and Kshudra Kushtha. Eka Kushtha is one of the Kshudra Kushtha described in different Ayurvedic classics. It is Vata-Kaphaj disorder. Ekakushtha has signs and symptoms i.e., Aswedanam (absence of sweating), Mahavastu (big size lesions) and Matsyasha kalopamam (scaling) which can be compared with Psoriasis. The exact etiology of Psoriasis is not known but many precipitating factors like genetic, dietary, immunological and psychological has been found. It is spreading fast because of unsuitable lifestyle changes such as dietary pattern, busy schedule and stress. The aim is to find out safe and effective treatment for psoriasis. Ayurveda plays an important role. There are three basic principles to treat any disease in Ayurveda i.e., Shodhana, Shamana and Nidana Parivarjana. Nidana Parivarjana is considered as the first line of treatment in most of the diseases. In Ayurveda diet plays a major role in the prevention and management of the disease. Sometimes Pathya and Apathya are the complete treatment of any diseases. So the main aim of this article is to focus on etiological factors of Ekakushtha and its management by various dietary regimens described in different Ayurvedic texts.

Most randomized controlled trials for psoriasis used placebo comparators despite the availability of effective treatments

BackgroundThe availability of effective treatments for psoriasis raises ethical questions about the use of a placebo group in therapeutic trials. We evaluated the use of the placebo over time in such trials. MethodsFrom trials in a living Cochrane review and network meta-analysis for psoriasis, we included trials comparing a biologic to a placebo or other systemic treatment. First, we tested the changes in placebo rate from 2001 to 2019 by linear regression, then constructed networks for 2004–2019 and evaluated the contribution of the placebo to the network meta-analysis estimates per trial and per comparison. ResultsWe included 81 trials (36,774 patients). The placebo rate did not decrease significantly over time. The proportion contribution of trials with a placebo decreased from 100% in 2004 to 86% in 2008 and 75% in 2019. However, the proportion contribution of trials without a placebo remained low (from 0% in 2004 to 25% in 2019). ConclusionThe design of future psoriasis trials should be reviewed to improve the number of patients to be included in a placebo group.

Treatments in psoriasis: from standard pharmacotherapy to nanotechnology therapy.

Psoriasis is a genetic chronic disease mediated by the immune system with systemic and cutaneous manifestations that can significantly deteriorate patients’ quality of life. Two–three percent of the population worldwide suffer from psoriasis and it imposes a substantial economic burden on patients. The aetiology is mainly related with genes and environmental factors. The pathophysiology of psoriasis is characterized by T cells and dendritic cells, antimicrobial peptides, genetic predispositions, lipoprotein-2, galactosin-3, fractalkine, vaspin, and human neutrophilic peptides, etc. in the progression of psoriasis. For patients with psoriasis, the traditional treatments include corticosteroids, vitamin D3 analogues, calcineurin inhibitors, methotrexate, cyclosporine, acitretin, phototherapy, and biological agents, etc. Nanodermatology is an emerging, multidisciplinary science that is gaining increasing recognition in the treatment of psoriasis. This review provides a summary of the pathophysiology, epidemiology, clinical diagnosis, and classical pharmacotherapy of psoriasis. The review also summarizes different nanotechnology therapies for effective treatment of psoriasis.

Management of Ekakushta, with special reference to Psoriasis, through Panchakarma: A Case Study

In Ayurveda all the skin diseases have been discussed under the ‘Vyadhi Kushtha’ Ekakushtha is one among Kshudra Kushtha. Kshudra are the Vyadhis which do not cause any major systemic involvement but their appearance disturbs mental condition of the patient as the disease doesn’t leave patient easily. They are not easy to treat as recurrence rate is very high. The clinical feature of Ekakushtha described represents remission, relapse and seasonal variation which are also present in Psoriasis. Modern medical science treats Psoriasis with PUVA, corticosteroids etc. But these therapies give serious side effects like hepatic and nephrotoxicity, bone marrow depression etc. Hence, it is the need of time to find out safe and effective treatment for Psoriasis and here Ayurveda plays an important role. Treatment modality of Ayurveda provides long lasting results and a better life to patients through its three basic principles i.e. Shodhana, Shamana and Nidan Parivarjana. Here we are reporting a 50-year-old female patient having symptoms of Ekakushtha since last 4 years. She was suffering from large round erythematous scaly patches over her B/L knee and elbow joint and also severe itching and dryness over affected lesions. There was no such significant past history of any other chronic illness. The patient was treated with Panchkarma i.e Vamana karma followed by Oral medications. Patient reported symptomatic improvement after the course of Vamana Karma.

The effectiveness and safety study of topical corticosteroids for psoriasis in adolescent and adult population treatment

Aim: to determine the efficacy and safety of clobetasol propionate compared with fluticasone propionate in the form of ointment for the treatment of psoriasis patients. Materials and methods. A total of 65 psoriasis patients were included in the study, 40 healthy individuals were included in the control group, all aged 14 to 65. Psoriasis patients were divided into 2 therapeutic groups: I – received topical treatment with fluticasone propionate; II – with clobetasol propionate. The severity of psoriasis was assessed by BSA and PASI index. Assessment of itching severity was carried out by a ten-point visual analogue scale. The quality of life was assessed according to the Ukrainian version of DLQI questionnaire. Results. PASI index averaged 16.50 ± 0.65 points, and BSA index was 9.30 ± 0.94 % in the examined patients before the treatment. On average, the DLQI index in patients with psoriasis before the treatment was 13.80 ± 0.27 points. PASI index was lower in psoriasis patients treated with clobetasol propionate compared with the therapeutic group I patients. The ΔPASI indicator (%) at the end of the treatment was significantly lower in patients from the I therapeutic group, compared with the group of patients who used clobetasol propionate for treatment of psoriasis. Patients who used clobetasol propionate had lower scores for pruritus and excoriation at the end of the treatment compared with patients from the I therapeutic group. The DLQI index at the end of the treatment was significantly higher in the I therapeutic group compared with its values in patients who used clobetasol propionate in the complex treatment. Conclusions. The use of topical corticosteroid clobetasol propionate in the form of ointment is the effective treatment for psoriasis, which causes a rapid regression of psoriatic rashes, a decrease in PASI and BSA indices, a decrease in pruritus and its objective signs, and indirectly improves the quality of life.

A review of secukinumab in psoriasis treatment.

Psoriasis is a systemic immunologic disorder associated with decreased quality of life and numerous co-morbidities, including psoriatic arthritis and cardiovascular disease. Secukinumab, a fully human IgG1 monoclonal antibody, selectively binds IL-17A and is approved by the US FDA and European Medicines Agency for moderate-to-severe plaque psoriasis and psoriatic arthritis. This review examines the efficacy and safety of secukinumab for the treatment of psoriasis using the literature retrieved from the PubMed database. In clinical trials, treatment with secukinumab led to rapid and sustained improvement in Psoriasis Area and Severity Index (PASI) scores, with PASI 90 response rates up to 68.5% at 5 years. Long-term clinical trial and real-world data have established secukinumab as a safe and effective treatment for psoriasis.

Topical delivery of clobetasol propionate loaded nanosponge hydrogel for effective treatment of psoriasis: Formulation, physicochemical characterization, antipsoriatic potential and biochemical estimation

Clobetasol propionate (CP), a superpotent topical corticosteroid, holds great promise for psoriasis treatment. However, common side effects like skin atrophy, steroidal acne, hypopigmentation and allergic contact dermatitis associated with it, hamper its utility for topical application. Taking this into consideration, the current work was aimed to fabricate CP loaded cyclodextrin nanosponge (CDNS) based hydrogel, to alleviate the aforementioned side effects, while controlling drug release. Nanosponges were crafted employing β-cyclodextrin (polymer) and diphenyl carbonate (cross linker) and evaluated appropriately. The selected formulation augmented 45 folds water solubility, with respect to pure CP. The formulation possessed entrapment efficiency (56.33 ± 0.94%), particle size (194.27 ± 49.24 nm) with polydispersitive index (0.498 ± 0.095), surface charge (−21.83 ± 0.95 mV) and drug release (86.25 ± 0.28%). Selected CP-CDNS were found crystalline and uniform in size. Further, in vitro cell viability analysis has been performed using THP1 cells to evaluate cytocompatibility of CP nanosponges. The chosen CP nanosponges were then embedded into Carbopol hydrogel, and characterized for rheological behaviour, spreadability, and texture profile. The developed nanoformulations were also assessed in vivo using mouse tail model. Histological and biochemical assessments have been conducted to explore their antipsoriatic activity via oxidative stress biomarkers. The degree of orthokeratosis was observed remarkably (p < 0.001) amplified by CP-CDNS14 hydrogel as compared to untreated group (control) and CP hydrogel. In addition, drug activity and change in epidermal thickness were found significant. Our findings altogether advocated the profound potential of prepared CP nanogel in the topical treatment of psoriasis, with improved patient compliance.

Fabrication of novel topical drug loaded elastic membrane vesicles of liposomes as a tool for dermal delivery in effective treatment of psoriasis

Fabrication of novel topical drug loaded elastic membrane vesicles of liposomes as a tool for dermal delivery in effective treatment of psoriasis

Multifaceted targeting of cationic liposomes via co-delivery of anti-IL-17 siRNA and corticosteroid for topical treatment of psoriasis

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.

Development and Characterization of Barbaloin Gel for the Safe and Effective Treatment of Psoriasis

Psoriasis is an inflammatory skin disease which cause inflammation to the skin and generally the symptoms includes white or red colour of irregular skin; the patches are developed and they are commonly itchy and scaly to the skin. Barbaloin is an herbal phytoconstituent which is obtained from the plant aloe vera leaf part. In the present study hydrogels formulation batches from F1 to F10 were prepared by using carbopol 934, Xanthan gum, carbopol 940, and carbopol 71G NF as a gelling agent. The prepared formulations from F1 to F10 were evaluated for their physical appearance, Grittiness, spreadability, Homogeneity, viscosity, pH, swelling index and microscopical evaluation. The changes in each evaluation parameter were examined at multiples concentration of each polymer. The effects of gelling agent in each formulation were observed and it will help us to justify the suitable range of polymer as a single or in combination with other gelling agent. From these studies it was found to be formulation F2, F4, F7 and F10 showing good gelling properties and further these four formulations are selected for In Vitro drug release studies. By In Vitro drug release kinetics study formulation F2 and F10 showed higher release as compared to F4 and F7. Furthermore, formulation F2 and F7 had good kinetic release study and showed non fickian drug release as the n value was between 0.8-0.9. Therefore, from the above release study parameters formulation F2 and F10 show the best optimized release characterstics as compare to the selected optimized formulations F4 and F7.&#x0D; Keywords: Psoriasis, Barbaloin, Hydrogel, Formulation and Evaluation.

Systematic development and characterization of curcumin-loaded nanogel for topical application

Curcumin (CUR) conventional formulation has poor oral bioavailability due to low solubility and low stability. Also, it extensively undergoes first-pass-metabolism showing low biological activity. The present work focuses on the systematic development and characterization of CUR-loaded Nanostructured Lipid Carrier (CUR-NLCs) having promising topical applications for skin diseases such as psoriasis. CUR-NLCs were prepared by using high-speed homogenization method. Quality by design approach was exploited to select out Critical Process Parameters i.e. homogenization speed (X1), homogenization time (X2), amount of lipid (X3), solid lipids (SL): liquid lipids (LL) (X4), and surfactant conc. (X5) using Plackett–Burman design and for obtaining critical quality attributes i.e. particle size (Y1) and entrapment efficiency (Y2) using Box–Behnken design. The developed NLCs were found to be nano-metric in size (189.4 ± 2.6 nm) with a low polydispersity index (0.262 ± 0.24), zeta potential (-21.45 ± 1.3 mV), and showed good encapsulation efficiency (86.72 ± 09%). Surface morphology determined by SEM and AFM revealed the spherical shape of the NLCs with a smooth surface. XRD studies showed NLCs in the amorphous state. After incorporation of NLCs into a nanogel, it was characterized for pH, rheological behavior, spreadability, in vitro occlusion, and in vitro release kinetics. The drug release from NLC in 24 h was found to be 60.2 ± 0.45% indicating a sustained release pattern. Ex vivo permeation studies revealed a good permeation flux (0.453 ± 0.76 µg/cm2.h) and retention (60.2 ± 0.45%) of CUR in the skin epidermis. Thus, developed CUR-NLCs can be a potential delivery system and a promising therapeutic approach for the effective treatment of psoriasis.

RETRACTED: Pluronic® F127 stabilized reduced graphene oxide hydrogel for the treatment of psoriasis: In vitro and in vivo studies

Psoriasis is a chronic inflammatory disease that can be effectively treated using topical cyclosporine. However, topical delivery is extremely challenging owing to the physicochemical nature of cyclosporine, as well as the thick psoriatic stratum corneum. In the present study, for the first time, we attempted to formulate a cyclosporine-loaded Pluronic® F127 stabilized reduced graphene oxide hydrogel to improve cyclosporine permeation and retention in the affected tissue for effective psoriasis treatment. The attachment of Pluronic® F127 on reduced graphene oxide was confirmed using Fourier transform infrared spectroscopy, Raman spectroscopy, and X-ray diffraction. The scanning electron microscopy image demonstrated a wrinkled and flattened nanosheet surface with Pluronic® F127 micelles. Ex vivo permeation data demonstrated an increase in cyclosporine permeation with increasing levels of reduced graphene oxide in the hydrogel. The hydrogel showed sufficient mechanical properties (texture analyzer report) for topical application, without any sign of irritation on rabbit skin. In the drug retention study, the C-P-rGO-500 hydrogel demonstrated maximum drug trapping inside the skin tissue. In the efficacy study in mice, the C-P-rGO-500 hydrogel decreased hyperplasia and tissue damage in psoriatic skin. Thus, the ability of the reduced graphene oxide nanocarrier to improve cyclosporine permeation, as well as retention in skin tissue, could be successfully utilized for effective psoriasis treatment, minimizing side effects encountered with oral and systemic routes.

781 IL1α, IL6, and GMCSF are Downstream Mediators of IL17A that Promote Asymmetric Stem Cell Self-Renewal in Psoriasis

Interleukin 17A (IL17A) is a key cytokine in psoriasis and IL17A antibody therapy is an effective treatment for psoriasis. We previously showed that IL17A increases asymmetric stem cell self-renewal divisions in human keratinocytes and plays a role in the hyperproliferation of the epidermis observed in psoriasis. We hypothesized that downstream IL17A-induced keratinocyte cytokines were mediators of the increased asymmetric stem cell self-renewal divisions of psoriasis. We studied cytokines produced by keratinocytes after IL17A treatment and determined their effects on asymmetric stem cell self-renewal divisions in human keratinocytes in vitro, using sister pair analysis.

Topical delivery of Tacrolimus using liposome containing gel: An emerging and synergistic approach in management of psoriasis

Psoriasis is a chronic relapsing inflammatory and hyperproliferative skin disease affecting quality of life. It affects an estimated 8 million Americans and more than 125 million people worldwide. The estimated cost to treat psoriasis in USA is over 13 billion US dollars per year. Treatment of psoriasis may include topical steroid-sparing agent, topical corticosteroids, phototherapy or biologics. Tacrolimus has 10-fold greater immunosuppressive activity than the ciclosporin A which has been recommended for effective treatment of psoriasis. However, it has been widely investigated using conventional formulation approaches which limit its clinical outcomes. It has poor cutaneous bioavailability when administered topically using conventional delivery approach, thus it has poor efficacy against the psoriasis. Low aqueous solubility and high degradation of Tacrolimus make it difficult to formulate as a liquid preparation. Moreover, Tacrolimus has narrow therapeutic index and thus it is essential to prevent its possible toxic effects when a modified release dosage form is administered. The present hypothesis aims to put forward to incorporate Tacrolimus into a novel lipid based nanocarrier system, which would be further loaded into a hydrogel base and evaluated for its target specific topic delivery. Due to the structural similarity of the lipid nanocarriers and skin, these vesicles would target the skin tissues effectively and treat psoriasis with minimum or no side effects. Thus, the proposed formulation would be a considerable value addition to the current therapeutic approaches used for psoriasis management.

Clinical Impact of Antibodies against Ustekinumab in Psoriasis: An Observational, Cross-Sectional, Multicenter Study

Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADAs on ustekinumab level and clinical response as assessed by the PASI. Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay and a drug-tolerant ELISA. Circulating ustekinumab levels were measured using an ELISA. ADAs were detected in 3.8% (95% confidence interval [CI]= 3.2-4.2) and in 10.6% (95% CI= 7.9-13.9) of patients using the radioimmunoassay and drug-tolerant ELISA, respectively. At least 85% of the ADAs were neutralizing. Compared with patients negative for ADAs, ADA positivity in the radioimmunoassay and drug-tolerant ELISA were associated with lower median ustekinumab levels (-0.62 μg/ml [95% CI=-1.190 to-0.30] and-0.74 μg/ml [95% CI=-1.09 to-0.47], respectively) and higher absolute PASI (6.6 [95% CI= 3.0-9.9] and 1.9 [95% CI= 0.4-4.0], respectively). Absence of detectable ustekinumab regardless of ADA status correlated with poor clinical outcome (median sample PASI 10.1, 6.5 [95% CI= 3.9-8.8] compared with patients positive for ustekinumab). In conclusion, substantially reduced drug exposure resulting from ADAs formation is associated with impaired clinical response.