Antipsoriatic Drug Research Articles

Novel Approaches and Applications of Nanotechnology in the Delivery of Topical Drugs for Psoriasis via Nanocarriers

Psoriasis is a non-contagious, continuing, auto-immune disease that mostly affects the skin, and about 2%-3% of the world's population suffers from it. In this review article, the primary focus is on the strategies involved in conventional therapies and the latest advances that have been recorded in metallic nano, polymer-based, and lipid-based formulations in the spectrum of anti-psoriatic drugs. Liposomes, ethosomes, solid lipid nanoparticles, micelles, and dendrimers are only some of the nanocarrier systems that have been extensively researched in relation to their potential use in nano formulations. This study incorporates patent applications that illustrate the nanoparticle's function in treating psoriasis. Hence, on the basis of an extensive literature survey, it is concluded that nano-formulations are a promising medium to treat a disease like psoriasis as they offer enhanced penetration, target-specific delivery, and improved efficacy. When applied to the study of biological systems and the development of novel medical technologies, nanobiotechnology offers potentially promising possibilities for the efficient use of nanoscale materials and processes. In this approach, nanotechnology and biotechnology are combined in order to develop nanoscale devices, materials, and systems that can be used for the diagnosis, treatment, and prevention of psoriasis. The future of the therapeutic effect of antipsoriatic drugs is dependent on both the benefits they have the ability to bring and the progress being made in the mass production of these carriers. Researching novel carrier systems or combination therapies is essential, but so is working to scale up existing technologies so they may be commercialised and used to benefit society at large.

Association between genetically proxied PPARG activation and psoriasis vulgaris: a Mendelian randomization study

Background Psoriasis is a common autoimmune disease in clinical practice, and previous observational studies have suggested that PPARG agonists such as Pioglitazone may be potential therapeutic agents. However, due to interference from various confounding factors, different observational studies have not reached a unified conclusion. We aim to evaluate the potential use of PPARG agonists for treating psoriasis from a new perspective through drug-targeted Mendelian randomization (MR) analysis. Materials and methods This study includes data on 8,876 individuals for acute myocardial infarction from GWAS, and LDL cholesterol data from 343,621 Europeans. FinnGen contributed psoriasis vulgaris data for 403,972 individuals. The DrugBank10 databases function to identify genes encoding protein products targeted by active constituents of lipid-modifying targets. A two-sample MR analysis and summary-data-based MR (SMR) analysis estimated the associations between expressions of drug target genes and symptoms of psoriasis vulgaris. A multivariable MR study was further conducted to examine if the observed association was direct association. Results SMR analysis revealed that enhanced PPARG gene expression in the blood (equivalent to a one standard deviation increase) was a protective factor for psoriasis vulgaris (beta = −0.2017, se = 0.0723, p = 0.0053). Besides, there exists an MR association between LDL mediated by PPARG and psoriasis vulgaris outcomes (beta = −3.9169, se = 0.5676, p = 5.17E-12). These results indicate that PPARG is a therapeutic target for psoriasis, suggesting that psoriasis may be a potential indication for PPARG agonists. Conclusion This study confirms that therapeutic activation of PPARG helps suppress the development of psoriasis. Psoriasis may be a new indication for PPARG agonists, such as Pioglitazone. In the future, new anti-psoriatic drugs could be developed targeting PPARG.

Synthesis and biological evaluation of novel isoxazoloquinone derivatives as potent STAT3-targeting antipsoriasis agents

Psoriasis is a troublesome scaling skin disease with no high-effective medication available by far. Signal transducer and activator of transcription 3 (STAT3) has recently been revealed as a crucial player in the pathogenesis and progression of psoriasis and emerged as an intriguing antipsoriatic drug target. Naturally occurring lapachol and its quinone analogs had been discovered as effective STAT3 inhibitors, however, their antipsoriatic effects are not well investigated. Previously, we have reported a series of isothiazoloquinone lapachol derivatives. Here, the antipsoriastic potentials of these isothiazoloquinones were investigated and, in addition, 35 novel isoxazoloquinone derivatives were prepared and studied for their anti-psoriasis properties. Among them, the most potent antipsoriatic compound B20 determined by in vitro test on HaCaT cells could directly bind to STAT3, reduce STAT3 level and inhibit STAT3 nuclear translocation. In vivo studies showed that topical application of B20 could effectively alleviate IMQ-induced psoriasis in mice with no obvious side effects. In addition, B20 inhibited the production of interleukin 17 (IL-17A), a STAT3-downstream cytokine essential for the progression of psoriasis, both in vitro and in vivo. Thus, isoxazoloquinone B20 is a potent STAT3-targeting antipsoriatic agent worth of further investigation.

Recent Approaches for the Topical Treatment of Psoriasis Using Nanoparticles.

Psoriasis (PSO) is a chronic autoimmune skin condition characterized by the rapid and excessive growth of skin cells, which leads to the formation of thick, red, and scaly patches on the surface of the skin. These patches can be itchy and painful, and they may cause discomfort for patients affected by this condition. Therapies for psoriasis aim to alleviate symptoms, reduce inflammation, and slow down the excessive skin cell growth. Conventional topical treatment options are non-specific, have low efficacy and are associated with adverse effects, which is why researchers are investigating different delivery mechanisms. A novel approach to drug delivery using nanoparticles (NPs) shows promise in reducing toxicity and improving therapeutic efficacy. The unique properties of NPs, such as their small size and large surface area, make them attractive for targeted drug delivery, enhanced drug stability, and controlled release. In the context of PSO, NPs can be designed to deliver active ingredients with anti-inflammatory effect, immunosuppressants, or other therapeutic compounds directly to affected skin areas. These novel formulations offer improved access to the epidermis and facilitate better absorption, thus enhancing the therapeutic efficacy of conventional anti-psoriatic drugs. NPs increase the surface-to-volume ratio, resulting in enhanced penetration through the skin, including intracellular, intercellular, and trans-appendage routes. The present review aims to discuss the latest approaches for the topical therapy of PSO using NPs. It is intended to summarize the results of the in vitro and in vivo examinations carried out in the last few years regarding the effectiveness and safety of nanoparticles.

Enhancement of Curcumin's Anti-Psoriatic Efficacy via Formulation into Tea Tree Oil-Based Emulgel.

Psoriasis is a chronic inflammatory skin disease characterized by the hyperproliferation and aberrant differentiation of epidermal keratinocytes. It is a debilitating condition that can cause significant physical and emotional distress. Natural anti-psoriatic agents have been investigated as alternatives to conventional allopathic medications, as they have notable limitations and drawbacks. Curcumin and tea tree oil are cost-efficient and effective anti-inflammatory medicines with less adverse effects compared to synthetic psoriasis medications. Our research endeavors to harness the therapeutic potential of these natural compounds by developing an herbal anti-psoriatic topical drug delivery system. This novel method uses curcumin and tea tree oil to create a bi-phasic emulgel drug delivery system. Formulations F1 (gel) and F2 (emulgel) have high drug content percentages of 84.2% and 96.7%, respectively. The emulgel showed better spreadability for cutaneous applications, with a viscosity of 92,200 ± 943 cp compared to the gel's 56,200 ± 1725 cp. The emulgel released 94.48% of the drugs, compared to 87.58% for the gel. These formulations conform to the zero-order and Higuchi models, and their stability over a three-month period is crucial. In vivo, the emulgel healed psoriasis symptoms faster than the usual gel. The gathered results confirmed the emulgel's potential as a drug delivery method, emphasizing the complementary benefits of tea tree oil and curcumin as an effective new therapy for psoriasis.

Investigation the efficacy of antipsoriatic drugs by blood plasma thermoanalysis

Psoriasis is an immune cell-mediated mainly inflammatory skin disease where patients may become asymptomatic after systemic drug therapies or nevertheless mild-to-moderate symptoms or exacerbating of either severe symptom should be detected. In addition to know the general change of blood plasma, the aim of the recent study was to detect the effect of antipsoriatic drug treatment to the patients’ symptoms by differential scanning calorimetry (DSC). The study included patients of both sexes who had different symptoms despite treatment with antipsoriatic medication (cytostatic agents, retinoids, biological treatment, n = 10 in each group). After the examination by dermatologist, the definition of symptoms severity was established on PASI (Psoriasis Area Severity Index) score. Blood plasma calorimetric changes were measured with calorimeter device. In the examined psoriatic patients, the thermodynamic parameters: denaturation temperature and calorimetric enthalpy of the transitions in proportion, corresponded to the degree of disease severity after targeted treatments with cytostatic or retinoid agents or following biological response modifier therapy. In conclusion, plasma DSC profiles were associated with response to antipsoriatic agents, which was associated with the presence or absence of symptoms after treatment.

Optimized dithranol-imiquimod-based transcutaneous immunization enables tumor rejection.

Transcutaneous immunization (TCI) is a non-invasive vaccination method promoting strong cellular immune responses, crucial for the immunological rejection of cancer. Previously, we reported on the combined application of the TLR7 agonist imiquimod (IMQ) together with the anti-psoriatic drug dithranol as novel TCI platform DIVA (dithranol/IMQ based vaccination). In extension of this work, we further optimized DIVA in terms of drug dose, application pattern and established a new IMQ formulation. C57BL/6 mice were treated on the ear skin with dithranol and IMQ-containing ointments together with ovalbumin-derived peptides. T cell responses were determined by flow cytometry and IFN-ɤ ELISpot assay, local skin inflammation was characterized by ear swelling. Applying the adjuvants on separate skin sites, a reduced number of specific CD8+ T cells with effector function was detectable, indicating that the local concurrence of adjuvants and peptide antigens is required for optimal vaccination. Likewise, changing the order of dithranol and IMQ resulted in an increased skin inflammatory reaction, but lower frequencies of antigen-specific CD8+ T cells indicating that dithranol is essential for superior T cell priming upon DIVA. Dispersing nanocrystalline IMQ in a spreadable formulation (IMI-Sol+) facilitated storage and application rendering comparable immune responses. DIVA applied one or two weeks after the first immunization resulted in a massive increase in antigen-specific T cells and up to a ten-fold increased memory response. Finally, in a prophylactic tumor setting, double but no single DIVA treatment enabled complete control of tumor growth, resulting in full tumor protection. Taken together, the described optimized transcutaneous vaccination method leads to the generation of a strong cellular immune response enabling the effective control of tumor growth and has the potential for clinical development as a novel non-invasive vaccination method for peptide-based cancer vaccines in humans.

Pathology and Treatment of Psoriasis Using Nanoformulations

Psoriasis (PSO) is an inflammatory skin condition that causes a variety of diseases and significantly decreases the life characteristics of patients, and substantially diminishes patients’ quality of life. PSO usually impairs the skin and is linked to various disorders. Inflammation pathology does not only damage psoriatic skin; it shows how PSO impinges other body parts. Many variables interact with one another and can impact the etiology of psoriasis directly or indirectly. PSO has an effect on approximately 2% of the world’s population, and significant progress has been made in comprehending and treating the alternative PSO by novel drug delivery systems. Topical, systemic, biological, biomaterials, and phototherapy are some of the useful therapies for PSO. Nonetheless, topical treatments remain the gold standard for treating moderate PSO. The applicability of several nanocarrier systems, such as lipid nanoparticles, metallic nanoparticles, and certain phytocompounds, has been briefly explored. The present review focuses mainly on traditional therapeutic strategies as well as on breakthroughs in nanoformulations and drug delivery methods for several anti-psoriatic drugs.

Effect of low-calorie diet on psoriasis severity index, triglycerides, liver enzymes, and quality of life in psoriatic patients with non-alcoholic fatty liver disease.

Chronic-plaque psoriasis is a chronic inflammatory dermatological disease. Obesity comorbidities, including non-alcoholic fatty liver disease, are highly prevalent in patients with chronic-plaque psoriasis. Recently, weight loss has been a highly recommended intervention to improve the severity of psoriatic symptoms, psoriasis-induced chronic systemic inflammation, psoriasis-associated cardiovascular risk factors, quality of life, and the efficacy of anti-psoriatic drugs. This study was designed to assess the effect of a 12-week low-calorie-diet intervention on aspartate transaminase, psoriasis severity (assessed via Psoriasis Area and Severity Index - PASI), alanine transaminase, quality of life (assessed via Dermatology Life Quality Index - DLQI), triglycerides, waist circumference (WC), and body mass index (BMI) in class I obese men with chronic-plaque and non-alcoholic fatty liver disease. Sixty men with age ≥ 18 years with class I obesity and with chronic plaque psoriasis and non-alcoholic fatty liver disease were included in the study. All participants were randomly assigned to one of two groups: the first group as the low-calorie-diet group (30 men received immunosuppressive drugs, followed a low-calorie diet, and increased their energy expenditure through a daily 15,000-step outdoor walking program for 12 weeks) and the second as the control group (30 men received immunosuppressive drugs only). The primary outcome consisted of the results of the area and severity index. Weight, BMI, WC, laboratory results such as triglycerides, liver enzymes (alanine transaminase and aspartate transaminase) as well as DLQI were considered as secondary outcomes. While no significant improvements were achieved in the measured variables of the control group, the low-calorie-diet group demonstrated significant improvement in all the measured variables. The results of the present study confirmed that 12-week low-calorie-diet intervention controls BMI, increases the response of psoriasis to pharmacological agents and improves the quality of life. Diet interventions significantly control the elevated hepatic enzymes (aspartate and alanine transaminases) and triglycerides in male patients with chronic-plaque psoriasis and non-alcoholic fatty liver disease.

Identification and mechanistic exploration of structural and conformational dynamics of NF-kB inhibitors: rationale insights from in silico and in vitro studies

Increased expression of target genes that code for proinflammatory chemical mediators results from a series of intracellular cascades triggered by activation of dysregulated NF-κB signaling pathway. Dysfunctional NF-kB signaling amplifies and perpetuates autoimmune responses in inflammatory diseases, including psoriasis. This study aimed to identify therapeutically relevant NF-kB inhibitors and elucidate the mechanistic aspects behind NF-kB inhibition. After virtual screening and molecular docking, five hit NF-kB inhibitors opted, and their therapeutic efficacy was examined using cell-based assays in TNF-α stimulated human keratinocyte cells. To investigate the conformational changes of target protein and inhibitor-protein interaction mechanisms, molecular dynamics (MD) simulations, binding free energy calculations together with principal component (PC) analysis, dynamics cross-correlation matrix analysis (DCCM), free energy landscape (FEL) analysis and quantum mechanical calculations were carried out. Among identified NF-kB inhibitors, myricetin and hesperidin significantly scavenged intracellular ROS and inhibited NF-kB activation. Analysis of the MD simulation trajectories of ligand–protein complexes revealed that myricetin and hesperidin formed energetically stabilized complexes with the target protein and were able to lock NF-kB in a closed conformation. Myricetin and hesperidin binding to the target protein significantly impacted conformational changes and internal dynamics of amino acid residues in protein domains. Tyr57, Glu60, Lys144 and Asp239 residues majorly contributed to locking the NF-kB in a closed conformation. The combinatorial approach employing in silico tools integrated with cell-based approaches substantiated the binding mechanism and NF-kB active site inhibition by the lead molecule myricetin, which can be explored as a viable antipsoriatic drug candidate associated with dysregulated NF-kB. Communicated by Ramaswamy H. Sarma

Preclinical study models of psoriasis: State-of-the-art techniques for testing pharmaceutical products in animal and nonanimal models.

Local and systemic treatments exist for psoriasis, but none can do more than control its symptoms because of its numerous unknown mechanisms. The lack of validated testing models or a defined psoriatic phenotypic profile hinders antipsoriatic drug development. Despite their intricacy, immune-mediated diseases have no improved and precise treatment. The treatment actions may now be predicted for psoriasis and other chronic hyperproliferative skin illnesses using animal models. Their findings confirmed that a psoriasis animal model could mimic a few disease conditions. However, their ethical approval concerns and inability to resemble human psoriasis rightly offer to look for more alternatives. Hence, in this article, we have reported various cutting-edge techniques for the preclinical testing of pharmaceutical products for the treatment of psoriasis.

The pharmaceutical market of medicines containing retinoids for the treatment of psoriasis in Ukraine, Poland and Kazakhstan

The aim of the work is to analyze the use of medicines containing retinoids for the treatment of psoriasis on the example of Ukraine, Poland and Kazakhstan.
 Materials and methods. The object of the study was antipsoriatic drugs, which are used for the treatment of psoriasis of local and systemic action, and are included in the official register of drugs of the studied countries. Regulatory documents of the State Expert Center of the Ministry of Health of Ukraine were involved in the analysis of the use of medicines for the treatment of psoriasis in Ukraine.
 The analysis of the availability of the considered medicines on pharmaceutical markets was carried out according to the data of the official websites of the State Register of Medicines (Ukraine), the Register of Medicines of Poland (Republic of Poland), data of the National Center for Expertise of Medicines and Medical Devices of the Republic of Kazakhstan (Republic of Kazakhstan).
 The following methods of logical and meaningful formulation of the problem, office marketing research, content analysis of publications in scientific and practically oriented medical and pharmaceutical publications, comparative analysis, tabular and graphic means of visual presentation of the obtained data were used in the work.
 The results. According to the results of the obtained data, an assortment of medicinal products containing retinoids of the studied countries, used for the treatment of psoriasis, was determined. The fate of domestic production in the countries was analyzed, the main active components from the group of retinoids used for the treatment of psoriasis in preparations of systemic and local action were updated.
 Conclusions. The role of retinoids in the treatment of psoriasis in Ukraine, Poland and Kazakhstan and the need to develop modern domestic medicines containing retinoids for the treatment of psoriasis have been determined

Recent Advancements in Topical Anti-Psoriatic Nanostructured Lipid Carrier-Based Drug Delivery.

Psoriasis is linked with unusual differentiation and hyperproliferation of epidermal keratinocytes that significantly impair the quality of life (QoL) of patients. The present treatment options only provide symptomatic relief and are surrounded by various adverse effects. Recently, nanostructured lipid carriers (NLCs) have emerged as next-generation nanocarriers with better physicochemical characteristics. The current manuscript provides background information on psoriasis, its pathophysiology, existing treatment options, and its limitations. It highlights the advantages, rationale, and mechanism of the permeation of NLCs for the treatment of psoriasis. It further gives a detailed account of various NLC nanoformulations for the treatment of psoriasis. In addition, tabular information is provided on the most relevant patents on NLCs for treating psoriasis. Lastly, light is shed on regulatory considerations related to NLC-like nanoformulations. In the treatment of psoriasis, NLCs display a sustained release drug profile, an ability to incorporate both hydrophobic and hydrophilic drugs, an enhancement in skin hydration, penetrability, retention, and bioavailability of the drug, along with reduced staining potential as compared to conventional ointments, and decreased side effects of drug molecules. This affirms the bright future of NLC nanoformulations in the treatment of psoriasis. However, academic industry collaboration and more sound regulatory controls are required to commercialize the NLC nanoformulations for psoriasis treatment.

Enantioselective Human Serum Albumin Binding of Apremilast: Liquid Chromatographic, Fluorescence and Molecular Docking Study.

The interaction between human serum albumin (HSA) and apremilast (APR), a novel antipsoriatic drug, was characterized by multimodal analytical techniques including high-performance liquid chromatography (HPLC), fluorescence spectroscopy and molecular docking for the first time. Using an HSA chiral stationary phase, the APR enantiomers were well separated, indicating enantioselective binding between the protein and the analytes. The influence of chromatographic parameters-type and concentration of the organic modifier, buffer type, pH, ionic strength of the mobile phase, flow rate and column temperature-on the chromatographic responses (retention factor and selectivity) was analyzed in detail. The results revealed that the eutomer S-APR bound to the protein to a greater extent than the antipode. The classical van 't Hoff method was applied for thermodynamic analysis, which indicated that the enantioseparation was enthalpy-controlled. The stability constants of the protein-enantiomer complexes, determined by fluorescence spectroscopy, were in accordance with the elution order observed in HPLC (KR-APR-HSA = 6.45 × 103 M-1, KS-APR-HSA = 1.04 × 104 M-1), showing that, indeed, the later-eluting S-APR displayed a stronger binding with HSA. Molecular docking was applied to study and analyze the interactions between HSA and the APR enantiomers at the atomic level. It was revealed that the most favored APR binding occurred at the border between domains I and II of HSA, and secondary interactions were responsible for the different binding strengths of the enantiomers.

Designing of novel nanoemulsions of retinol using box Behnken design for psoriasis

Psoriasis is a chronic inflammatory disease, which is triggered by genetic and environmental factors, has been found to be associated with comorbidities like psoriatic arthritis, Crohn's disease etc. Retinol acetate is an effective, first line anti-psoriatic drug for Psoriasis but researchers have indicated toxicity in case of its overdose. Present study is an attempt to design Retinol Acetate Nanoemulsion RANE with optimum dosage, improved hydration and penetration, hence better absorption. Box Behnken model of Design Expert version 12 was used for the optimization process to prepare O/W Nanoemulsion. RANE was evaluated by pH, viscosity, conductivity, particle size analysis and responses like % drug content and % in-vitro drug release at different time intervals were experimentally recorded. Predicted value and experimental value of % drug content was found to be 83.84 ± 0.12 and 80.24 ± 1.14 respectively with relative error of 3.6 ± 1.02. While these values for in-vitro drug release at 90 min interval was 47.21 ± 0.21 % and 48.23 ± 2.90 respectively with relative error of 1.02 ± 2.69. It’s p-value was found to be 0.02, which is significant and f value was 0.27 which is non-significant, VIF value was 1.0–1.03 and Ri 2 range was found to be 0–0.03 which proves the model is fit for optimization. These findings for optimized formulation might suggest promising results in effective treatment of psoriasis on further investigation.

Nanoscale Topical Pharmacotherapy in Management of Psoriasis: Contemporary Research and Scope.

Psoriasis is a typical dermal condition that has been anticipated since prehistoric times when it was mistakenly implicit in being a variant of leprosy. It is an atypical organ-specific autoimmune disorder, which is triggered by the activation of T-cells and/or B-cells. Until now, the pathophysiology of this disease is not completely explicated and still, many research investigations are ongoing. Different approaches have been investigated to treat this dreadful skin disease using various anti-psoriatic drugs of different modes of action through smart drug-delivery systems. Nevertheless, there is no ideal therapy for a complete cure of psoriasis owing to the dearth of an ideal drug-delivery system for anti-psoriatic drugs. The conventional pharmacotherapy approaches for the treatment of psoriasis demand various classes of anti-psoriatic drugs with optimum benefit/risk ratio and insignificant untoward effects. The advancement in nanoscale drug delivery had a great impact on the establishment of a nanomedicine-based therapy for better management of psoriasis in recent times. Nanodrug carriers are exploited to design and develop nanomedicine-based therapy for psoriasis. It has a promising future in the improvement of the therapeutic efficacy of conventional anti-psoriatic drugs. The present manuscript aims to discuss the pathophysiology, conventional pharmacotherapy, and contemporary research in the area of nanoscale topical drug delivery systems for better management of psoriasis including the significance of targeted pharmacotherapy in psoriasis.

In Vitro and Ex Vivo Evaluation of Fluocinolone Acetonide-Acitretin-Coloaded Nanostructured Lipid Carriers for Topical Treatment of Psoriasis.

Psoriasis is chronic autoimmune disease that affects 2-5% of the global population. Fluocinolone acetonide (FLU) and acitretin (ACT) are widely used antipsoriatic drugs that belong to BCS classes II and IV, respectively. FLU exhibits side effects, such as skin irritation and a burning sensation. ACT also shows adverse effects, such as gingivitis, teratogenic effects and xerophthalmia. In the present study, topical nanostructured lipid carriers (NLCs) were fabricated to reduce the side effects and enhance the therapeutic efficacy. FLU-ACT-coloaded NLCs were prepared by the modified microemulsion method and optimized by the Box-Behnken model of Design Expert® version 12. The optimization was based on the particle size (PS), zeta potential (ZP) and percentage of encapsulation efficiency (%EE). The physicochemical analyses were performed by TEM, FTIR, XRD and DSC to assess the morphology, chemical interactions between excipients, crystallinity and thermal behavior of the optimized FLU-ACT-coloaded NLCs. The FLU-ACT-coloaded NLCs were successfully loaded into gel and characterized appropriately. The dialysis bag method and Franz diffusion cells were used for the in vitro release and ex vivo permeation studies, respectively. The optimized FLU-ACT-coloaded NLCs had the desired particle size of 288.2 ± 2.3 nm, ZP of -34.2 ± 1.0 mV and %EE values of 81.6 ± 1.1% for ACT and 75 ± 1.3% for FLU. The TEM results confirmed the spherical morphology, while the FTIR results showed the absence of chemical interactions of any type among the ingredients of the FLU-ACT-coloaded NLCs. The XRD and DSC analyses confirmed the amorphous nature and thermal behavior. The in vitro study showed the sustained release of the FLU and ACT from the optimized FLU-ACT-coloaded NLCs and FLU-ACT-coloaded NLC gel compared with the FLU-ACT suspension and conventional gel. The ex vivo study confirmed the minimal permeation of both drugs from the FLU-ACT-coloaded NLC gel.

Association of Elevated ASO Titer with Plaque and Guttate Psoriasis

Objectives: To determine the association of elevated ASO titer with plaque and guttate psoriasis. Study Design: Case control study. Place and Duration: Department of Dermatology, Shaheed Mohtrama Benazir Bhutto Medical University (SMBBMU), Larkana during from 22nd January 2018 to 21st July 2018 Materials & Methods: A total of 30 patients with plaque or guttate psoriasis and 30 controls, 20 to 60 years of age of either gender were included. Patients taking systemic anti-psoriatic drugs, CRF and erythroderma were excluded. After this throat swabs were taken and pathogenic organism was identified by gross colony morphology and types of hemolysis on culture media. β-hemolysis indicated growth of Streptococcus pyogens. Antistreptolysin O titer (ASO titer) was measured and titer >200 IU/ml was taken as elevated. Results: Mean age was 40.92 ± 10.62 years. Out of 60 patients, 40 (66.67%) were males and 20 (33.33%) were females with male to female ratio of 2:1. Frequency of elevated ASO titer in patients with plaque and guttate psoriasis was found in 13 (43.33%) and in 04 (13.33%) controls with p-value of 0.014 and odds ratio of 2.97. Conclusion: This study concluded that concluded that there is positive association of elevated ASO titer with plaque and guttate psoriasis. Keywords: Psoriasis, Throat Infection, ASO Titer

FORMULATION AND EVALUATION OF CLOBETASOL-17-PROPIONATE-LOADED CARBOXYMETHYL CHITOSAN NANOPARTICLE

Objective: Formulation and evaluation of clobetasol-17-propionate-loaded carboxymethyl chitosan nanoparticle. Psoriasis is a chronic skin disorder caused due to the autoimmune factors. It has a detrimental psychological and physiological impact on patients due to the emergence of apparent skin. The systemic therapy with anti-psoriatic drugs such corticosteroids, immunosuppressant, and gene suppressors causes severe side effects. As a result, increasing the effectiveness and safety of the aforementioned medicines when applied topically would be extremely useful in avoiding the side effects associated with the systemic route of administration. Methods: Chitosan (CS) has not been widely used in the clinic applications but due to its limited solubility and poor mechanical characteristics. CS, on the other hand, is chemically changed to form carboxymethyl (CMC), which is soluble at both neutral and basic pH. Chemical modifications can also be used to attach different functional groups and control hydrophobic, cationic, and anionic properties. CMC is a promising carrier that might possibly traverse the thick scales of psoriatic skin since it is a penetration enhancer that allows drug diffusion through either the transcellular or paracellular pathways. Comparative study is done using CMC as a polymer and CD as a polymer. Results: CP-loaded CMC nanoparticles show better result results than CP-loaded CD polymer. Conclusion: Clobetasol-17-propionate-loaded carboxymethyl chitosan nanoparticle shows better results with improved solubility.

Evaluation of methotrexate-loaded surfactants, ceramides and cholesterol-based lamellar phases as a topical treatment for psoriasis.

Psoriasis is a chronic inflammatory skin disorder. Oral or subcutaneous methotrexate (MTX) is a first-line antipsoriatic treatment, whose adverse effects can be observed even at low doses. To minimize systemic side effects, antipsoriatic drugs should be administered topically, since they could permeate the stratum corneum. As liquid crystals with lamellar phase (LP) can be helpful in promoting skin permeation, this work evaluated two MTX-loaded LPs (C1CH and C1CHCE), based on stearic acid, cholesterol and ceramides, like topical treatments for mice with imiquimod-induced psoriasis. C1CH and C1CHCE were topically administered to mice with imiquimod-induced psoriasis. Dexamethasone cream was used as positive treatment control. Skin histology and inflammation biomarkers were assessed. C1CH and C1CHCE exhibited marked immunomodulatory effects and induced extensive microstructural skin remodelling on the epidermis and dermis. These formulations increased keratinization score, epidermis thickness, inflammatory infiltrate, hair follicle hypertrophy and vascular congestion in the dermis. C1CH and C1CHCE also attenuated IL-10 upregulation and upregulated IL-1, IFN-γ, TNF-α and prostaglandin E2 levels, as well as myeloperoxidase, N-acetyl-β-d-glucosaminidase and cyclooxygenase 2 activity compared with untreated psoriatic animals. Although liquid crystals have been reported as good options for carrying topical drugs, they need to be carefully assessed on a case-by-case basis.