Mouse Tail Model Research Articles

Optimisation and in-vivo evaluation of extracted Karanjin loaded liposomal topical formulation for treatment of psoriasis in tape-stripped mouse model

Aim The present work is focus on development of anti-psoriasis activity of Karanjin (isolated from Pongamia pinnata seed oil) loaded liposome based lotion for enhancement of skin permeation and retention. Method Karanjin was isolated using liquid-liquid extraction method and characterised by HPLC analysis and partition coefficient. Further, isolated Karanjin was loaded into liposomes using thin-film hydration technique and optimised by Box-Behnken design. Selected optimised batch was characterised their mean diameter, PDI, zeta potential, and entrapment efficiency, morphology (by TEM), FTIR and ex-vivo skin retention. Additionally, Karanjin loaded liposomes were formulated into lotion and characterise their rheological, spreadability, texture, ex-vivo skin permeation & retention, stability and anti-psoriatic activity in mouse tail model. Result The yield of Karanjin from seed oil was 0.1% w/v and have lipophilic nature. The optimised liposomal formulation showed 195 ± 1.8 nm mean diameter, 0.271 ± 0.02 PDI, −27.0 ± 2.1 mV zeta potential and 61.97 ± 2.5% EE. TEM image revel the spherical shap of liposome surrounded by single phospholipid bilayer and no interection between drug and excipients. Further, lotion was prepared by 0.1% w/v carbopol and found to 615 mPa.sec viscosity, good thixotropic behaviour, spreadability and texture. There was 22.44% increase in drug permeation for Karanjin loaded liposomal lotion compared to pure Karanjin lotion, confirm by ex-vivo permeation and retention. While, in-vivo study revel the liposomal lotion of Karanjin was found to have 16.09% higher drug activity then 5% w/w conventional Karanjin lotion. Conclusion Karanjin loaded liposomal lotion have an effective anti-psoriatic agent and showed better skin permeation and retention than the conventional Karanjin lotion.

Novel Chitosan Nanoparticles Loaded with Methotrexate for Topical Treatment of Psoriasis.

In this work, CS NPs were prepared by the ionic gelation method and encapsulated with MTX to treat psoriasis dermally. A major drawback of using MTX to treat psoriasis is its limited diffusion through the skin, which may cause insufficient penetration of MTX into the basal layer of the epidermis, where psoriatic cells are generated. Nanoparticles have been used to enhance MTX diffusion through the skin. The system prepared in this work is expected to direct the drug to psoriasis cells by enhancing the drug diffusion through the skin, which will increase the amount of the drug reaching the epidermis. This is expected to enhance the effectiveness of the drug and to decrease its systemic side effects. Five formulations of Chitosan nanoparticles were prepared and loaded with Methotrexate using the ionic gelation technique. Particle size, dispersity, charge, loading capacity and encapsulation efficacy were measured. Characterization of prepared nanoparticles was conducted to confirm the formation of CS-NPs, successful encapsulation of MTX and its compatibility with other formulation components. In vitro drug release from CS-NPs, its permeation and accumulation in rats' skin were explored. Finally, the anti-psoriatic activity was assessed using the "mouse tail model." The results showed that the sizes ranged from 132.13 ± 0.70 to 300.60 ± 4.81 nm, where SEM demonstrated the spherical and uniform distribution of the NPs. The surface charge of all NPs was highly positive and ranged from 20.22 ± 1.10 to 30.90 ± 0.70 mV. Further, the EE% and LC% of the nanoparticles were in the range of 77.72%-92.70% and 17.90%-21.81%, respectively. in vitro, the release of methotrexate from the nanoparticles was sustained. Additionally, both the permeation and retention of drugs within the skin were enhanced significantly using this system. Eventually, orthokeratosis% and drug activity% showed significant superiority of MTX-CS NPs over the free drug in treating psoriasis in model mice. In conclusion, MTX-CS NPs can be used to enhance the treatment of psoriasis topically.

Analysis of CD4+ T-helper-associated hub gene signature and immune dysregulation via RNA-sequencing data in a mouse tail model of lymphedema.

T-helper cells play an essential role in the progression of lymphedema. This study aimed to explore the biological significance of T-helper cell-associated genes (THAGs) in a mouse tail model of lymphedema by RNA-sequencing (RNA-seq) data. The expression profiles of a murine model of secondary lymphedema were obtained from European Nucleotide Archive (ENA) database. Differentially expressed genes (DEGs) were screened and the enrichment analysis of DEGs was conducted. THAGs were constructed by crossing the T-helper-related gene sets obtained from Molecular Signatures Database with DEGs. Protein-protein interaction (PPI) network analysis was utilized to establish T-helper-associated hub genes (THAHGs). Single-sample gene set enrichment analysis (ssGSEA) was employed to decipher differences in immune cell infiltration. The correlation between THAHGs and immune infiltration was calculated by Pearson correlation analysis. Receiver operating characteristic (ROC) curves of THAHGs were drawn to evaluate their diagnostic properties. Additionally, potential drugs and upstream transcription factors (TFs) were predicted based on THAHGs. Enrichment analysis showed that lymphedematous tissue presented higher activation of biological process (BP) of T-helper 1 (Th1), T-helper 2 (Th2), T-helper 17 (Th17). The immune infiltration analysis further calculated that the relative immune abundance of follicular B cells, memory B cells, M1 macrophage, and CD4+ Tm cells was significantly elevated while the relative immune abundance of neutrophils and plasma cells were down-regulated in lymphedema. We established a list of THAHGs consisting of eight hub genes, compassing Cd4, Foxp3, Irf4, Ccr6, Il12rb1, Batf, Il1b, Cd74. THAHGs were shown to be significantly interrelated and related to immune infiltration by Pearson correlation analysis. ROC curves showcased that the area under curve (AUC) values of THAHGs were larger than 0.70. Gata3 was the most potential TF and thalidomide might be the immunoregulatory drug for lymphedema based on THAHGs. Biological pathways associated with T-helpers were significantly enriched in mouse lymphedema tissue. The relative immune infiltration abundance of M1 macrophage, CD4+ Tm cells, and T-helper cells was higher in the lymphedema group. Besides, we identified the THAHGs containing eight genes, namely, Cd4, Foxp3, Irf4, Ccr6, Il12rb1, Batf, Il1b, and Cd74. The THAHGs were closely correlated with immune infiltration results and with good diagnostic properties.

Treatment with YIGSR peptide ameliorates mouse tail lymphedema by 67 kDa laminin receptor (67LR)-dependent cell-cell adhesion

Impaired microcirculation can cause lymphatic leakage which leads to a chronic swelling in the tissues of the body. However, no successful treatment gives any protection against lymphedema due to the lack of well-revealed pathophysiology of secondary lymphedema. Binary image of laminin immunohistochemical expression revealed that distribution of laminin expression localized during surgically induced lymphedema. 67 kDa laminin receptor (67LR) mRNA expression showed a peak at during lymphedema exacerbation. Since the response of 67LR molecules may affect the prevention of inflammation and edema, here we have hypothesized that 67LR ligand of YIGSR peptide could permit reconstructive environment for amelioration of lymphedema and evaluated the effect of YIGSR in a mouse tail model of lymphedema. Indeed, intra-abdominal injections of YIGSR for the first 3 days after inducing lymphedema in the mouse tail model reduced the tail lymphedema on day 14 by 27% (P = 0.035). Histology showed that YIGSR treatment protected lymphedema impairment in epidermis and dermis, and it also inhibited the expansion of intercellular spaces and enhanced especially cell adhesion in the basement membrane as revealed by transmission electron microscopy. Interestingly, the treatment also reduced the local expression of transforming growth factor (TGF)β. Further elucidation of the mechanisms of 67LR-facilitated lymphangiogenesis contributes to find potential targets for the treatment of lymphedema.

Topical application of aerial portion of Acalypha indica Linn ameliorates psoriasis in rodents: Evidences from in vivo and in silico studies

Ethanopharmacological relevanceAcalypha indica Linn. is a weed, used traditionally for different skin diseases such as eczema and dermatitis in various parts of India. There are no previous in vivo studies reported on the antipsoriatic potential of this medicinal plant. AimThe aim of this study was to investigate antipsoriatic activity of coconut oil dispersion of aerial portion of Acalypha indica Linn. Few lipid-soluble phytoconstituents of this plant were subjected to molecular docking studies on different targets to determine phytoconstituent responsible for antipsoriatic activity. MethodsVirgin coconut oil dispersion of aerial portion of the plant was prepared by mixing three parts of coconut oil and one part of powdered aerial portion. The acute dermal toxicity was determined according to OECD guidelines. Mouse tail model was used to evaluate the antipsoriatic activity. Molecular docking of phytoconstituents was carried out using Biovia Discovery Studio. ResultsIn acute dermal toxicity study,the coconut oil dispersion was found to be safe up to the dose of 20000 mg/kg. The dispersion exhibited significant antipsoriatic activity (p < 0.01) at the dose of 250 mg/kg; at 500 mg/kg dose, the activity was similar that of 250 mg/kg dose. In the docking study of the phytoconstituents, 2-methyl anthraquinone was found to be responsible for antipsoriatic activity. ConclusionThis study provides new evidence of Acalypha indica Linn as antipsoriatic plant and justifies its traditional use. Computational studies also endorse the results obtained via acute dermal toxicity study and mouse tail model for evaluation of antipsoriatic potential.

Formulation and Evaluation of Nanogel used for the Treatment of Psorasis

Context: Although several formulation strategies have been developed for the treatment of psoriasis, there is an unmet need for optimization of its therapy. Objective: The objective was to develop a nanogel composed of Acitretin (ACT) loaded nanostructured lipid carrier (ACT-NLC) and to evaluate its potential in imiquimod-induced psoriasis model to ameliorate symptoms of psoriasis. Materials and methods: The developed control (CNGs) nanogels, acitretin loaded nanogels (ActCNGs) were characterized by UV and FTIR. Results and discussion: The systems were found to be spherical in shape with a size range of 98±10, and 138±8 nm having zeta potential values of +28±3 and +27±3 mV for CNGs and ActCNGs respectively. The in vitro haemolysis assay revealed that all the nanogel systems are blood compatible. The systems exhibited higher swelling and release at acidic pH. The ex vivo skin permeation studies using porcine skin confirmed the higher deposition of the systems at epidermal and dermal layers, which was confirmed further by fluorescent imaging. The in vivo anti-psoriatic activity study using Perry's mouse tail model and skin safety studies confirmed the potential benefit of the system for topical delivery of acitretin in psoriasis.

Phytochemical evaluation and anti-psoriatic activity of the ethanolic extract of the leaves of Thespesia populnea

Psoriasis is a chronic, mild and common inflammatory skin condition. Still an ideal treatment for psoriasis, effective, safe, convenient, and economical is not available. In this scenario, the search for suitable alternative treatments with minimal side effects is necessary. Plants can be effective and alternative in this regard. Therefore, this article discusses the leaves of the plants Thespesia populnea (Malvaceae) that are traditionally used in the treatment of psoriasis. The present study aimed to assess anti-psoriatic activity. The dried leaves of the plants were subjected to soxhlation with 95% ethanol and phytochemical studies were performed. The anti-psoriatic activity was evaluated by the Mouse-Tail model. It is a relatively sensitive and reproducible morphometric method that allows quantitative evaluation of the effects of anti-psoriatics through epidermal differentiation. Extracts were applied topically at a dose of 500mg/kg over 14 days and at the end, the animals were sacrificed, longitudinal histological sections were made of the tail skin and the degree of orthokeratosis was determined. It was significantly (P &lt;0.05) increased by the ethanolic extract of Thespesia populnea (52.86±2.86) compared to the control (17.30±4.09). In relative epidermal thickness, the ethanolic extract of Thespesia populnea (92.68±8.8) showed a significant difference (P &lt;0.05) compared to the control (100±10.7). The data obtained suggest that the selected plant has anti-psoriatic activity and confirms its traditional use in the treatment of psoriasis.

A new perspective for psoriasis: Dithranol nanosponge loaded hydrogels

We developed dithranol nanosponge integrated Carbopol hydrogel (DTHNS-HG) as a novel perspective for psoriasis management. Dithranol was chosen as antipsoriatic moiety for this system. In this study, our objective was to fabricate and evaluate DTHNS-HG for in vivo anti-psoriatic activity using mouse tail model. Nanosponges (NSs) were synthesized using diphenyl carbonate and β-cyclodextrin employing melt method and appropriately characterized. The selected nanosponges were then embedded into Carbopol hydrogels and assessed for viscosity, spreadability and texture analysis. The developed formulations were further evaluated in vivo for antipsoriatic potential (% drug activity,% orthokeratosis and relative changes in epidermal thickness). Additionally, oxidative stress markers were also checked in mouse tail samples. DTH loaded cyclodextrin nanosponges were successfully fabricated and displayed acceptable mean particle size (274.6 ± 43.54 nm with 0.545 PDI) and zeta potential (-28.3 ± 6.34 mV). Further, DTHNS amalgamated hydrogel showed satisfactory results in terms of spreadability, viscosity and texture profiles. The degree of orthokeratosis was significantly (p < 0.05) increased with DTHNS-HG (0.5 and 1.0% w/v) and marketed ointment, as compared to the untreated group (control). Similarly, the drug activity and changes in epidermal thickness were found significant. Our findings from present investigations suggested a new cargo for delivery of DTH in topical medicinal strategies for psoriasis. Hence, this novel hydrogel showed promising outcomes for psoriasis.

Single-cell RNA sequencing of subcutaneous adipose tissues identifies therapeutic targets for cancer-associated lymphedema

Cancer-associated lymphedema frequently occurs following lymph node resection for cancer treatment. However, we still lack effective targeted medical therapies for the treatment or prevention of this complication. An in-depth elucidation of the cellular alterations in subcutaneous adipose tissues of lymphedema is essential for medical development. We performed single-cell RNA sequencing of 70,209 cells of the stromal vascular fraction of adipose tissues from lymphedema patients and healthy donors. Four subpopulations of adipose-derived stromal cells (ASCs) were identified. Among them, the PRG4+/CLEC3B+ ASC subpopulation c3 was significantly expanded in lymphedema and related to adipose tissue fibrosis. Knockdown of CLEC3B in vitro could significantly attenuate the fibrogenesis of ASCs from patients. Adipose tissues of lymphedema displayed a striking depletion of LYVE+ anti-inflammatory macrophages and exhibited a pro-inflammatory microenvironment. Pharmacological blockage of Trem1, an immune receptor predominantly expressed by the pro-inflammatory macrophages, using murine LR12, a dodecapeptide, could significantly alleviate lymphedema in a mouse tail model. Cell–cell communication analysis uncovered a perivascular ligand-receptor interaction module among ASCs, macrophages, and vascular endothelial cells. We provided a comprehensive analysis of the lineage–specific changes in the adipose tissues from lymphedema patients at a single-cell resolution. CLEC3B was found to be a potential target for alleviating adipose tissue fibrosis. Pharmacological blockage of TREM1 using LR12 could serve as a promising medical therapy for treating lymphedema.

The Kinetics of Lymphatic Dysfunction and Leukocyte Expansion in the Draining Lymph Node during LTB4 Antagonism in a Mouse Model of Lymphedema.

The mechanisms of lymphedema development are not well understood, but emerging evidence highlights the crucial role the immune system plays in driving its progression. It is well known that lymphatic function deteriorates as lymphedema progresses; however, the connection between this progressive loss of function and the immune-driven changes that characterize the disease has not been well established. In this study, we assess changes in leukocyte populations in lymph nodes within the lymphatic drainage basin of the tissue injury site (draining lymph nodes, dLNs) using a mouse tail model of lymphedema in which a pair of draining collecting vessels are left intact. We additionally quantify lymphatic pump function using established near infrared (NIR) lymphatic imaging methods and lymph-draining nanoparticles (NPs) synthesized and employed by our team for lymphatic tissue drug delivery applications to measure lymphatic transport to and resulting NP accumulation within dLNs associated with swelling following surgery. When applied to assess the effects of the anti-inflammatory drug bestatin, which has been previously shown to be a possible treatment for lymphedema, we find lymph-draining NP accumulation within dLNs and lymphatic function to increase as lymphedema progresses, but no significant effect on leukocyte populations in dLNs or tail swelling. These results suggest that ameliorating this loss of lymphatic function is not sufficient to reverse swelling in this surgically induced disease model that better recapitulates the extent of lymphatic injury seen in human lymphedema. It also suggests that loss of lymphatic function during lymphedema may be driven by immune-mediated mechanisms coordinated in dLNs. Our work indicates that addressing both lymphatic vessel dysfunction and immune cell expansion within dLNs may be required to prevent or reverse lymphedema when partial lymphatic function is sustained.

A Murine Tail Lymphedema Model.

Lymphedema is extremity swelling caused by lymphatic dysfunction. The affected limb enlarges because of accumulation of fluid, adipose, and fibrosis. There is no cure for this disease. A mouse tail model that uses a focal full thickness skin excision near the base of the tail, resulting in tail swelling, has been used to study lymphedema. However, this model may result in vascular comprise and consequent tail necrosis and early tail swelling resolution, limiting its clinical translatability. The chronic murine tail lymphedema model induces sustained lymphedema over 15 weeks and a reliable perfusion to the tail. Enhancements of the traditional murine tail lymphedema model include 1) precise full thickness excision and lymphatic clipping using a surgical microscope, 2) confirmation of post-operative arterial and venous perfusion using high resolution laser speckle, and 3) functional assessment using indocyanine green near infrared laser lymphangiography. We also use tissue nanotransfection technology (TNT) for novel non-viral, transcutaneous, focal delivery of genetic cargo to the mouse tail vasculature.

Nano-elastic modulus of tendon measured directly in living mice

The nano-biomechanical environment of the extracellular matrix is critical for cells to sense and respond to mechanical loading. However, to date, this important characteristic remains poorly understood in living tissue structures. This study reports the experimental measurement of the in vivo nano-elastic modulus of the tendon in a mouse tail model. The experiment was performed on the tail tendon of an 8-week-old C57BL/6 live mouse. Mechanical loading on tail tendons was regulated by changing both voltage and frequency of alternating current stimulation on the erector spinae. The nano-elastic modulus of the tail tendon was measured by atomic force microscope. The nano-elastic modulus showed significant variation (2.19–35.70 MPa) between different locations and up to 39% decrease under muscle contraction, suggesting a complicated biomechanical environment in which cells dwell. In addition, the nano-elastic modulus of the tail tendon measured in live mice was significantly lower than that measured in vitro, suggesting a disagreement of tissue mechanical properties in vivo and in vitro. This information is important for the designs of new extracellular biomaterial that can better mimic the biological environment, and improve clinical outcomes of musculoskeletal tissue degenerations and associated disorders.

Inflammation Precedes Fat Deposition in an Experimental Model of Lymphedema.

Background: Chronic lymphedema is a common complication of lymphatic obstruction, particularly after cancer treatment, characterized by an increased volume of the affected extremity, partly caused by the accumulation of excessive adipose tissue. The relationship between lymph vessels' obstruction and fat deposit is, however, poorly understood. Objective: Our central hypothesis was that the inflammatory process caused by lymph stasis precedes the adipocyte differentiation and fat deposition. Methods and Results: We used a modified mouse tail model to produce secondary lymphedema. Animals were treated with dexamethasone, or the procedure was performed in nitric oxide synthase 2 (NOS2)-deficient mice to evaluate the role of inflammation in lymphedema formation. Adipose tissue (Lipin) and inflammatory markers (IL-6, MCP-1, and F4-80) were analyzed in histological samples and by quantitative polymerase chain reaction. We observed an increased deposition of fat into the affected area that starts 3 weeks after lymph vessel ligation; it further increased after 6 weeks. Genes involved in the inflammatory process were upregulated before adipocyte maturation. Treatment with dexamethasone or the use of inducible nitric oxide synthase knockout mice blocked the inflammatory reaction and inhibited the accumulation of fat distal to the lymphatic obstruction. Conclusion: In the modified mouse tail lymphedema, inflammation precedes adipogenesis. Our data suggest that MCP-1 and nitric oxide may be potential targets for lymphedema management.

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.

Evaluation of anti-psoriatic activity of selected phytochemicals on UV-induced psoriasis in mouse tail model

Objectives: To evaluate anti-psoriatic activity of Phytochemicals on UV-Induced psoriasis in mouse tail model. Materials and Methods: Anti-psoriatic activity of selected phytochemicals on UV-Induced psoriasis in mouse tail model. The animals were dividing into 05 groups and each group contain 5 animals. Disease control group did not receive any treatment only exposure to UV-light, vehicle control treated with simple ointment, standard group treated with salicylic acid (1%w/w) ointment, remaining group are treated 1% and 2% selective phytochemical at two concentrations of ointment to topically on the tail skin. And the data were analysed using one way ANOVA followed by two-way ANOVA (Dunnett’s multiple comparisons test). Results: There was significant decrease in epidermal thickness (P &lt; 0.05) as compared with control group. In 2% phytoconstituents has shown a significant reduction in the total epidermal thickness 8.4****±0.748, 7.6**±0.6781 and 8*±0.8366 in geraniol, glycyrrhizic acid and ellagic acid treated group, when compare to the disease induced animal, there was no lesion of Munro’s microabscess, capillary loop dilation along with elongation of rete ridges in the section of skin of rats. Psoriasis Severity Index was reduced in test treated groups as compared with that of disease control group. It was slowly reduced to 2nd week, totally (55-70%) reduction in PSI is observed at the time of third week of treatment period. Conclusion: The result of the study showed that the 2% of geraniol, ellagic acid, glycyrrhizicacid and hesperidin, exhibited significant activity on UV-induced psoriasis in rodents. The study implies that selected phytoconstituents are a promising research for further investigations to prove its anti-psoriatic activity.

Formulation and evaluation of a topical liposomal gel containing a combination of zedoary turmeric oil and tretinoin for psoriasis activity

This study was to develop a combination of zedoary turmeric oil (ZTO) and tretinoin (TRE)-loaded liposomal gel as a topical drug delivery system. We used a combination of single-factor experiment and orthogonal experiment to systematically optimize encapsulation process of the compound liposomes. The optimized liposome vesicles were incorporated into Carbopol gel matrix and studied by continuous in vitro (skin penetration and retention) and in vivo (anti-psoriatic activity using mouse vaginal model and mouse tail model) experiments. The optimized liposomes had an entrapment efficiency (EE) of ZTO was (64.63 ± 1.00)%, EE of TRE was (90.33 ± 0.72)%, drug loading (DL) of ZTO was (9.09 ± 0.14)%, DL of TRE was (1.43 ± 0.02)%, particle size of 257.41 ± 7.58 nm, polydispersity index (PDI) of 0.10 ± 0.04 and zeta potential of −38.77 ± 0.81 mV. Transmission electron microscopy showed liposomes had a regular spherical surface. After 1-month storage at (4 ± 2)°C, the optimized liposome preparations maintained its stability. In vitro study indicated that liposome formulations could significantly prolong the penetration of drugs into the hair follicles of mice and keep more drugs in the skin compared with conventional gel formulations. In vivo study showed that liposomal gel was more effective than conventional gel in treating psoriasis and had a significant dose-dependent effect on psoriasis. In summary, liposomal gel is expected to be an ideal carrier for topical drug delivery systems of ZTO and TRE.

Abstract 182: Orally Administered 9-cis Retinoid Acid Improves Functional Lymphatic Drainage In Post-surgical Lymphedema

Purpose: We have previously shown that daily intraperitoneal administration of 9-cis Retinoic Acid (9-cis RA) is associated with increased lymphangiogenesis and lymphatic clearance in a mouse tail model of lymphedema. Since an oral dosing regimen would have higher clinical translatability, we sought to determine if orally administered 9-cis RA was similarly effective in preventing lymphedema. Methods: In a mouse tail model, secondary lymphedema was induced by excising 5 mm of skin circumferentially and obliterating all remaining lymphatics utilizing injection of methylene blue and the operative microscope. Twenty-five sex-matched FVB mice aged weighing between 20 and 30 grams were assigned to one of three groups: control (n=8), low-dose 9-cis RA (n=8), and high-dose 9-cis RA (n=9). 9-cis retinoic acid was dissolved in soybean oil, and vehicle control consisted of soybean oil. Low-dose 9-cis RA mice and high-dose 9-cis RA mice received doses of 10 mg/kg and 30 mg/kg respectively, and each mouse was given 0.15 mL of solution via oral gavage daily. The tail images were taken every week for 6 weeks and analyzed with ImageJ software. On POD42, mice tails were injected intradermally with indocyanine green (ICG), and fluorescence was captured and quantified via NOVADAQ Spy Fluorescence Imaging at 0, 1, 3, 6, 12, 24, 48, 72, and 96 hours. Lastly, a comprehensive metabolic panel was performed on the blood serum of each mouse. Results: The percentage change in tail volume of the low 9-cis RA group was statistically lower than the control group at all time points beginning on POD14 (p < 0.05). At POD14, the mean change in tail volume for the low 9-cis RA group and control groups were 18.11% and 69.26% respectively (p < 0.001). The percentage change in fluorescence from hour 1 post-ICG injection was significantly different between low-dose 9-cis RA group and the control group at 72, 96, and 120 hours (p < 0.05). The high-dose 9-cis RA group did not show a significant difference in tail volume change or fluorescence change relative to the control group. In addition, the high-dose 9-cis RA group demonstrated mild cutaneous irritation in the perioral and throat regions while these adverse events were not observed in the low-dose 9-cis RA group. The chemistry panel results showed no significant differences between control and both 9-cis RA groups, and there was no significant difference in weights for any groups at any time point. Conclusion: Treatment with orally administered 9-cis RA at an oral dose of 10 mg/kg attenuates the volume change associated with lymphedema and improves lymphatic drainage in a mouse tail model. These findings offer a potential preventative treatment for patients at risk of developing secondary lymphedema.

Thymoquinone-loaded lipid vesicles: a promising nanomedicine for psoriasis

BackgroundPsoriasis, a recurrent, chronic inflammatory disorder of skin, is a common problem in middle age and elderly people. Thymoquinone (TQ), a lipid soluble benzoquinone is the major active ingredient of volatile oil of Nigella sativa (NS), possesses good anti-psoriatic activity. However, its hydrophobicity, poor aqueous solubility, and photosensitive nature obstructs its development. Therefore, in the present research work, ethosomal vesicles (EVs) loaded with TQ were assessed for its anti-psoriatic potential employing mouse-tail model.MethodsTQ-loaded EVs were prepared by cold method, and characterized for various essential attributes, viz. particle size, morphology, percent drug entrapment, flexibility, rheological and textural analysis, and skin absorption. The optimized formulation was finally evaluated for anti-psoriatic activity on Swiss albino mice employing mouse-tail model for psoriasis.ResultsThe spherical shaped vesicles were in the nanosize range, and had high flexibility. The EVs incorporated hydrogel was rheologically acceptable and resulted in substantial TQ retention in the skin layers. The % anti-psoriatic drug activity was observed to be substantially better in the case of TQ-loaded ethosomal gel vis-à-vis plain TQ, NS extract, and marketed formulation.ConclusionsThe promising outcomes of the current studies ratify the superiority of TQ-loaded phospholipid-based vesicular systems for the management of psoriasis over other studied test formulations. This study, thus open promising avenues for topical application of TQ in the form of EV hydrogel.

Eudragit RS100 based microsponges for dermal delivery of clobetasol propionate in psoriasis management

Clobetasol propionate (CP), a super potent dihalogenated topical corticosteroid for psoriasis, displays common side effects like allergic contact dermatitis, steroid acne, skin atrophy, hypo-pigmentation and systemic absorption, on topical application. Hence, entrapment of CP in an appropriate carrier system could minimise the aforementioned side effects, while controlling its percutaneous absorption. Therefore, motive behind current work was to fabricate and evaluate CP loaded microsponges (MS). The microsponges were successfully crafted by employing quasi-emulsion solvent diffusion method. For preparation of MS, organic phase comprising CP, Eudragit RS 100 and dichloromethane was added to aqueous phase (polyvinyl alcohol solution), while stirring. During optimization of MS formulations, factors (drug: polymer ratio, aqueous and organic phase volume) affecting the physical properties of microsponges were also investigated. The prepared microsponges were found to possess particle size in the range 12.2 ± 8.2–45.80 ± 12.3 μm, entrapment efficiency: 60.00 ± 0.06 to 96.37 ± 0.04 % and drug release: 60.60 ± 0.13 to 92.82 ± 0.15 %. Additionaly, CP loaded microsponges were evaluated for topography, thermal and photostability. Finally, optimized CPMS were incorporated into Carbopol gel base, which was subsequently evaluated. In vitro release of CPMS was compared with plain CP and release results were fitted into different kinetic models. CPMS formulation followed zero order kinetics indicating release of drug at constant rate, with absence of initial burst release. This delivery system resulted in extended CP release and its maximum therapeutic activity, with minimum toxic effects. In vivo antipsoriatic activity of CPMS gel performed using mouse tail model exhibited significant therapeutic efficacy in comparison to plain CP gel, which was further supported by the histopathological findings.

Evaluation of Antipsoriatic Activity of Topical Curcumin by using Mouse Tail Model

Background; Psoriasis is a one of the common dermatological diseases with no curative topical or systemic treatment, Curcumin is a naturally occurring phytochemical present in turmeric; it was traditionally used for the treatment of many skin diseases. This study was designed to evaluate the anti-psoriatic effect of curcumin preparations. Objectives; this study aimed to examine the probability of anti-psoriatic activity of topical curcumin by using mouse tail model. Methods; The extracted curcumin was assessed for antipsoriatic activity using a mouse tail model of psoriasis. 18 animals were divided into three groups (6 animals each). Group A: control group (cream base treated group) Group B: (treated with curcumin cream 1%) Group C: (treated with curcumin cream 2 %) Granular layer formation, epidermal thickness and drug activity were taken as an evaluating parameter to detect the efficacy of the new preparation. Results; The local application of curcumin 1%, 2% on the mouse tail skin produced a significant differentiation in the epidermis, as seen from its degree of orthokeratosis ( 43.4± 0.75) and ( 44.4 ±0.98 ) respectively when compared with the negative control (17.06±2.5 ). Conclusion;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Topical curcumin have anti-psoriatic activity&nbsp; and&nbsp; seems to be well tolerated on skin since the incidence of side effects was limited except staining of&nbsp; skin by an orange color.