Mouse Tail Model Research Articles

Comparative assessment of efficacy and safety potential of multifarious lipid based Tacrolimus loaded nanoformulations

The present work reports the development, optimization and characterization of novel lipid based nanoformulations viz., Liquid crystalline nanoparticles (LCNP), solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) and liposomes loaded with Tacrolimus (Tac) for topical delivery. Different nanoformulations were developed after screening lipids and suitable surfactants depending upon emulsification ability. The various nanoformulations were then optimized (to achieve higher entrapment efficacy, lower particle size, PDI and zeta potential), characterized and loaded into gel. The gels loaded with nanoformulations were also characterized depending upon rheology and viscosity. The gels were analyzed for in vitro drug release, HaCaT cell lines studies and skin permeation studies. The in vivo efficacy studies were carried out using mouse tail model and skin irritation studies using Draize patch test and measurement of TEWL. The developed nanoformulations showed optimum particle size (<200 nm), polydispersity index (PDI < 0.3), zeta potential (≥−10 mV) and higher entrapment efficiency (>85%). The nanoformulations showed higher penetration of Tac into skin. Tac-LCNP, Tac-SLN, Tac-NLC and Tac-liposomes loaded gels showed 14, 11.5, 12.5 and 3.7 folds increment in dermal bioavailability respectively, in comparison to free Tac loaded gel and 2.5, 2 and ∼2 folds augmentation in dermal bioavailability respectively as compared to Tacroz™ Forte. In case of Tac-liposomes, the dermal bioavailability was lower as compared with the marketed formulation, Tacroz™ Forte. Despite, the increased bioavailability into the skin, the developed nanoformulations showed no significant skin irritation. The above mentioned nanoformulations were able to achieve greater penetration of Tac into the skin as compared to marketed ointment of Tac, Tacroz™ Forte.

Enhanced anti-psoriatic efficacy and regulation of oxidative stress of a novel topical babchi oil (Psoralea corylifolia) cyclodextrin-based nanogel in a mouse tail model

Psoriasis is a proliferative inflammatory skin disorder with relapsing episodes. Herein, the efficacy of babchi oil (BO) loaded nanostructure gel was evaluated for antipsoriatic activity and oxidative stress biomarkers assessment using mouse tail model. BO was entrapped into cyclodextrin-based nanocarriers (360.9 ± 19.55 nm), followed by incorporation into Carbopol gel and characterised for viscosity, spreadability, and texture analysis. The gels were topically applied on mouse-tails once daily for fourteen days. Evaluation of antipsoriatic activity as determined by histopathological observations of orthokeratotic epidermis revealed two times higher efficacy of BO nanogel in comparison to the native BO gel. Further, significantly enhanced superoxide dismutase (SOD) and reduced glutathione (GSH) levels, and diminished malondialdehyde (MDA) and nitrite (NO) levels revealed that prepared nanogels played a major role in the management of reactive oxygen species (ROS) associated in psoriasis pathogenesis. Hence, this study provides strong evidence for use of cyclodextrin-based nanogels as a safe and better delivery carrier of BO for management of psoriasis.

Development and Evaluation of a New In Vivo Volume Measuring System in Mouse Tail Lymphedema Model.

Backgrounds: Secondary lymphedema is a common complication of parasitization and breast or gynecologic cancer therapy; however, options for the treatment of lymphedema are ineffective and limited. A mouse tail model is one of the most successful animal models for a lymphatic study. Lymphedema of the mouse tail is characterized by increases in the volume of the extremity caused by accumulation of tissue fluid, proliferation of fibroblasts and adipocytes, and excessive production of collagen. However, the study of lymphedema using mouse has been plagued with difficulty in directly assessing physiologic changes owing to limitations in the measurement of the mouse tail volume. Furthermore, the mouse tail volume cannot be obtained using the general in vivo measurement method such as volumetric water displacement. Methods and Results: Lymphatic researchers have used the truncated cone formula to approximate the volume as used in the numerical approximation of a cylindrical figure. Although this formula is simple and easy to use, it has difficulties of repeatability and accuracy because the measurement procedure is highly subjective and the accuracy depends on the number of divided segments on the tail. In this article, two novel volumetric measurement methods for the mouse tail model were introduced. The methods were evaluated and compared using three mice with surgically created lymphedema on the tails. Conclusions: The two continuous measuring methods showed a possibility to improve the conventional method by continuous measurement using visual and physical detecting methods. The proposed methods facilitate the extraction of longitudinal section-specific information, which can be an important clue in a lymphatic study.

Antipsoriatic effect of fatty acid enriched fraction of Vernonia anthelmintica Willd. fruits

Ethnopharmacological relevanceVernonia anthelmintica has been utilized conventionally as an ingredient in Ayurveda and traditional Uighur medicine for management of various skin ailments, and scientific data's have substantiated its use in treating vitiligo, dermatosis and leucoderma. The present investigation was focused to evaluate the antipsoriatic activity of V. anthelmintica fruit extracts and fractions. Materials and methodsOintment containing dichloromethane (DCM) and methanol (MeOH) extracts at topical dose of 2.5% and 5% (w/w) was evaluated using mouse tail model of psoriasis. Bioactivity-guided fractionation (F1-F7) of most active extract was carried out and fractions were again subjected to mouse tail model. Further the activity of bioactive fraction was confirmed in HaCaT (human keratinocyte) cell line using MTT (3-(4,5-dimethylthiazol-2-yl)− 2,5-diphenyltetrazolium bromide) assay and its chemical characterization was done via gas chromatography mass spectrometry (GC-MS). ResultsThe dichloromethane extract (5%, w/w) showed statistically significant (* p < 0.05) antipsoriatic activity (66.97 ± 2.68%) with respect to control (25.45 ± 1.80%) and equivalent to that of the standard drug, retino-A 0.05%, (72.47 ± 2.14%) in terms of degree of orthokeratosis, whereas methanol extract (5%, w/w) showed significant (* p < 0.05) differentiation (45.86 ± 2.02%) in comparison to the control group. Out of all fractions, F6 showed statistically significant (* p < 0.05) antipsoriatic activity (69.27 ± 2.76%) with respect to control and equivalent to that of the standard. F6 (15.6–1000 µg/ml) showed dose-dependent inhibition of HaCaT cell lines proliferation which suggests keratinocyte modulating activity of V. anthelmintica. Chemical characterization of F6 revealed that essential fatty acids (i.e., linoleic acid, palmitic acid, oleic acid and stearic acid) formed the bulk of bioactive fraction. ConclusionAmeliorative effect of V. anthelmintica in psoriasis might be attributed to the presence of essential fatty acids and thus corroborates its traditional use in the treatment of skin ailments.

Pivotal role of Acitretin nanovesicular gel for effective treatment of psoriasis: ex vivo-in vivo evaluation study.

The goal of the current study was to explore the potential benefits of Acitretin (Act) nanovesicular gel as a prospective antipsoriatic topical delivery system counteracting the drug challenges in terms of its extremely low aqueous solubility, instability, skin irritation, and serious systemic adverse effects. Act-loaded niosomes were successfully developed, entirely characterized, and optimized. Further evaluation of the optimized formula was conducted regarding its stability and ex vivo cytotoxicity on different cell lines. The optimized niosomal vesicles were then incorporated in gel base matrix and investigated by sequential ex vivo (skin permeation and deposition) and in vivo (skin irritation and antipsoriatic activity using mouse tail model) experiments. The optimized Act-loaded niosomes (span 60:cholesterol molar ratio 1:1) were spherical in shape and exhibited the highest entrapment efficiency (90.32±3.80%) with appropriate nanosize and zeta potential of 369.73±45.45 nm and −36.33±1.80 mV, respectively. Encapsulation of the drug in the nanovesicles was further emphasized by differential scanning calorimetric and powder X-ray diffraction studies. After 3 months storage at 4±1°C, the optimized formula preserved its stability. Act nano niosomal gel produced a remarkable enhanced ex vivo permeation profile up to 30 h and significant drug deposition in the viable epidermal–dermal layers compared with those of Act gel. The pronounced antipsoriatic activity of the medicated nano niosomes was proved ex vivo in HaCaT cells (a keratinocyte cell line). Topical application of Act nano niosomal gel to mouse tail model further established its distinct in vivo antipsoriatic superiority in terms of significantly higher orthokeratosis, drug activity, and reduction in epidermal thickness compared with the control and other gel formulations. Also, negligible skin irritation and better skin tolerability of Act nanovesicular gel were revealed by primary irritation index and histopathologic examination.

English

The mouse tail model was used to measure and compare antipsoriatic activity of Acalypha wilkesiana and Culcasia scandens with that of earlier reported Kigelia africana stem methanol extract by the same authors, with the objective of finding out which of these plant extracts can be a better drug option for the treatment of psoriasis. The results obtained showed that topically administered extracts (50-200 mg/ml) induced a significant and dose-dependent increase in %orthokeratosis in the epidermis of the mice tails. % orthokeratosis values were 35.5-43.4 (A. wikesiana), 29.7-47.4 (K. africana), 31.9-36.5 (C. scandens) for the methanol ointments; 29.3-36.2 (A. wikesiana), 32.3-58.2 (K. africana), 29.40-56.2 (C. scandens) for the hexane extracts. In general, the methanol extracts produced higher % othokeratosis. No deterioration in the general condition of the mice in any group was observed. However, erythema was observed on the tails of the mice on which the K. africana stem methanol extract ointment (200 mg/ml) was applied. No tail erythema was observed in any other group. Application of the ointments resulted in the softening of the tails. In general, the irritation potentials of the ointments were relatively low when compared to that induced by dithranol a drug commonly used in the treatment of psoriasis. Only the A. wilkesiana methanol extract ointment (200 mg/ml) showed greater than 40% drug activity. Thus, A. wilkesiana appears to be the better plant for use in possible drug development for the management and cure of psoriasis because A. wilkesiana ointment showed more prospects of being an antipsoriatic topical agent when compared to C. scandens or K. africana, as the drug activity of the methanol extract of this plant was greater than 40% and quite similar to that of K. africana without the corresponding irritation potential or erythema. Key words: Psoriasis, mouse-tail model, Acalypha wilkesiana, Culcasia scandens, Kigelia africana, dithranol drug activity, irritation potential.

Quantitative Evaluation of the Antipsoriatic Activity of Flavonoids from Cassia tora Linn. Leaves

The plant Cassia tora L. (Caesalpiniaceae) is traditionally claimed to be useful in the treatment of psoriasis and other skin diseases. In the previous work, three flavonoids viz quercetin-3-O-β-d-glucuronide (I), luteolin-7-O-β-glucopyranoside (II) and formononetin-7-O-β-D-glucoside (III) were isolated from Cassia tora leaves. As an extension of work, the present study aimed to evaluate antipsoriatic activity of these flavonoids using in vitro and in vivo model. In vitro antiproliferant assay of the ethanol extract and isolated flavonoids was done on HaCaT cell lines. Mouse tail test was used for the evaluation of antipsoriatic activity of ethanol extract (100, 200 and 400 mg/kg b.w.) and bioactive flavonoids (50 mg/kg b.w.) in Swiss albino mice. Maximum antiproliferant activity was shown by isolated flavonoids II and III (58.65 and 87.74 μg/ml) in HaCaT cell inhibition assay. In mouse tail model, a significant reduction in epidermal thickness and significant orthokeratosis with respect to control was observed in groups treated with ethanol extract (200 and 400 mg/kg) and isolated flavonoids II, III. From the above data, the flavonoid II (luteolin-7-O-β-glucopyranoside) showed maximum antiproliferant activity and significant orthokeratosis. This study suggests the potential antipsoriatic activity of the flavonoids of Cassia tora and a need for studies to understand the mechanism of action.

Modified Mouse Models of Chronic Secondary Lymphedema: Tail and Hind Limb Models

Postsurgical secondary lymphedema is usually a progressive and lifelong condition lacking any curative treatment. The aim of this study was to develop new, simple surgical mouse models of chronic lymphedema, better simulating chronic nature of human postsurgical lymphedema. Two experimental mouse models of secondary lymphedema were created surgically without radiation by modifications of the previously described methods: the tail model and the hind limb model. Lymphedema formation was clinically assessed and quantitatively evaluated by measuring circumferences and limb volumes. Postmortem specimens were assessed histologically to examine the efficacy of the models. In the tail models, although a substantial frequency of tail necrosis (30.0%) was noted and the increase in circumference was maintained for only limited times postoperatively depending on the particular tail model, the overall success rate was 65.0%. In the mouse hind limb model, the overall success rate was 88.9%, and the increased circumference and limb volume were maintained over the entire study period of 8weeks. The overall success rate of the mouse hind limb model was significantly higher than that of the mouse tail model(s). We have successfully established modified mouse tail and hind limb lymphedema models via only surgical techniques without radiation, which have characteristics of chronic secondary lymphedema. The mouse hind limb model has a higher success rate than the mouse tail model and has advantages of having the healthy contralateral hind limbs as an internal control.

Demonstration of the Usefulness of Optical Coherence Tomography in Imaging a Mouse Tail Model of Lymphedema

To investigate the usefulness of optical coherence tomography (OCT) for imaging lymphedema, we directly compared it to other histological methods in a mouse model of lymphedema. We performed detailed imaging of the lymphedema lesion on a mouse tail. We imaged the mouse tail in vivo with OCT and created histopathological samples. We constructed a spectrometer-based OCT system using a fiber-optic Michelson interferometer. The light was directed to 50:50 couplers that split the light into reference and sample arms. Backscattered light from a reference mirror and the sample produced an interference fringe. An OCT image of the lymphedema model revealed an inflammatory reaction of the skin that was accompanied by edema, leading to an increase in the light attenuation in the dermal and subcutaneous layers. Similar to OCT image findings, histological biopsy showed an inflammatory response that involved edema, increased neutrophils in epidermis and subdermis, and lymphatic microvascular dilatation. Furthermore, the lymphedema model showed an increase in thickness of the dermis in both diagnostic studies. In the mouse tail model of lymphedema, OCT imaging showed very similar results to other histological examinations. OCT provides a quick and useful diagnostic imaging technique for lymphedema and is a valuable addition or complement to other noninvasive imaging tools.

Acitretin and aloe-emodin loaded chitin nanogel for the treatment of psoriasis

The present study focuses on the development of an effective topical nanogel formulation of two anti-psoriatic drugs; Acitretin (Act) and Aloe-emodin (AE) using natural polymer chitin. Simple regeneration chemistry was used to prepare Chitin Nanogel Systems (CNGs). The developed control chitin (CNGs) nanogels, acitretin loaded chitin nanogels (ActCNGs) and aloe-emodin loaded chitin nanogels (AECNGs) were characterized by DLS, SEM, FTIR, XRD and TG-DTA. The systems were found to be spherical in shape with a size range of 98±10, 138±8 and 238±6nm having zeta potential values of +28±3, +27±3 and +25±6mV for CNGs, ActCNGs and AECNGs 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 and aloe-emodin in psoriasis.

Use of Granulocyte-Colony Stimulating Factor as adjuvant therapy in patients with recurrent pregnancy failure

The present study focuses on the development of an effective topical nanogel formulation of two anti-psoriatic drugs; Acitretin (Act) and Aloe-emodin (AE) using natural polymer chitin. Simple regeneration chemistry was used to prepare Chitin Nanogel Systems (CNGs). The developed control chitin (CNGs) nanogels, acitretin loaded chitin nanogels (ActCNGs) and aloe-emodin loaded chitin nanogels (AECNGs) were characterized by DLS, SEM, FTIR, XRD and TG-DTA. The systems were found to be spherical in shape with a size range of 98 ± 10, 138 ± 8 and 238 ± 6 nm having zeta potential values of +28 ± 3, +27 ± 3 and +25 ± 6 mV for CNGs, ActCNGs and AECNGs 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 and aloe-emodin in psoriasis.

NETosis and lack of DNase activity are key factors in Echis carinatus venom-induced tissue destruction

Indian Echis carinatus bite causes sustained tissue destruction at the bite site. Neutrophils, the major leukocytes in the early defence process, accumulate at the bite site. Here we show that E. carinatus venom induces neutrophil extracellular trap (NET) formation. The NETs block the blood vessels and entrap the venom toxins at the injection site, promoting tissue destruction. The stability of NETs is attributed to the lack of NETs-degrading DNase activity in E. carinatus venom. In a mouse tail model, mice co-injected with venom and DNase 1, and neutropenic mice injected with the venom, do not develop NETs, venom accumulation and tissue destruction at the injected site. Strikingly, venom-induced mice tail tissue destruction is also prevented by the subsequent injection of DNase 1. Thus, our study suggests that DNase 1 treatment may have a therapeutic potential for preventing the tissue destruction caused by snake venom.

Anti-inflammatory and lymphangiogenetic effects of low-level laser therapy on lymphedema in an experimental mouse tail model.

The aim of the present study was to investigate the therapeutic mechanism of low-level laser therapy (LLLT) in the mouse tail lymphedema model. Six-week-old female mice were classified into the laser treatment group, sham treatment group, and surgical control group (10 mice per group). LLLT was administered daily for 10 min from the surgical day to 11 days (12 times). Macrophage activation and lymphatic vessel regeneration were evaluated through immunohistochemical staining with anti-F4/80 and anti-LYVE-1 antibodies, respectively, at 12 days post-procedure. Quantitative real-time polymerase chain reaction (qPCR) was performed to measure messenger RNA (mRNA) expression of vascular endothelial growth factor A, B, C, R1, R2, and R3 (VEGF-A, VEGF-B, VEGF-C, VEGFR1, VEGFR2, and VEGFR3) at 12 days post-procedure. Student's t and one-way ANOVA tests were performed for statistical analyses. Significance was defined as p < 0.05. The thickness of the tail rapidly increased until 6 days in the laser and sham groups. The mice in the laser group showed a significantly decreased thickness compared with the sham group at 10 and 12 days. Immunohistochemistry assay revealed that LLLT reduced inflammation and induced new lymphatic vessel growth. qPCR showed that expressions of VEGFR3 were (p = 0.002) increased in the laser group. These results suggest that LLLT has anti-inflammatory and lymphangiogenetic effects for the management of lymphedema.

Liposomal fusidic acid as a potential delivery system: a new paradigm in the treatment of chronic plaque psoriasis

Chronic plaque psoriasis is an inflammatory skin disease affecting 2–3% of the world population. With increasing understanding of the progress of disease and its causes, bacterial infection is reported to be one of the potential reasons. In this regard, fusidic acid (FA), a steroidal antibiotic, has been a drug of choice which could play an important role by virtue of its unique mechanism of action. Despite many topical formulations of FA in practice, drug-delivery issues like permeability in the prevailing infectious conditions and stability of the drug are yet the challenges not been covered so far from the formulation development perspective. For these issues, liposomes, on account of their carrier-specific properties, have been suggested as delivery tools to fulfill the expectations. In the present work, FA liposomes (FA-LP) were prepared and characterized for its varied traits such as size (420–740 nm), surface charge, morphology, percent skin permeation (>75%), and retention (1.620 ± 0.8 mg/cm2). Confocal laser scanning microscope (CLSM) images revealed appreciable cell-uptake of fluorescent dye-loaded liposomes. In stability, FA-LP proved to be stable with respect to drug leakage and vesicle size. In vivo studies using the mouse tail model, FA-LP, are found significantly better (p < 0.05) vis-à-vis conventional one with improved efficacy in and around the target site by the carrier-effect. Hence, the work suggests for the possibility of a better FA liposome-based formulation as a potential option in addressing the infectious challenges of psoriasis.

Regulation of inflammation and fibrosis by macrophages in lymphedema.

Lymphedema, a common complication of cancer treatment, is characterized by inflammation, fibrosis, and adipose deposition. We have previously shown that macrophage infiltration is increased in mouse models of lymphedema. Because macrophages are regulators of lymphangiogenesis and fibrosis, this study aimed to determine the role of these cells in lymphedema using depletion experiments. Matched biopsy specimens of normal and lymphedema tissues were obtained from patients with unilateral upper extremity breast cancer-related lymphedema, and macrophage accumulation was assessed using immunohistochemistry. In addition, we used a mouse tail model of lymphedema to quantify macrophage accumulation and analyze outcomes of conditional macrophage depletion. Histological analysis of clinical lymphedema biopsies revealed significantly increased macrophage infiltration. Similarly, in the mouse tail model, lymphatic injury increased the number of macrophages and favored M2 differentiation. Chronic macrophage depletion using lethally irradiated wild-type mice reconstituted with CD11b-diphtheria toxin receptor mouse bone marrow did not decrease swelling, adipose deposition, or overall inflammation. Macrophage depletion after lymphedema had become established significantly increased fibrosis and accumulation of CD4(+) cells and promoted Th2 differentiation while decreasing lymphatic transport capacity and VEGF-C expression. Our findings suggest that macrophages home to lymphedematous tissues and differentiate into the M2 phenotype. In addition, our findings suggest that macrophages have an antifibrotic role in lymphedema and either directly or indirectly regulate CD4(+) cell accumulation and Th2 differentiation. Finally, our findings suggest that lymphedema-associated macrophages are a major source of VEGF-C and that impaired macrophage responses after lymphatic injury result in decreased lymphatic function.

Solid lipid nanoparticles-loaded topical gel containing combination drugs: an approach to offset psoriasis

Aim: The primary aim of present work was to develop effective combination drug therapy for topical treatment of psoriasis.Methods: Betamethasone dipropionate and calcipotriol loaded solid lipid nanoparticles (CT-BD-SLNs) were prepared by hot melt high shear homogenization technique, which were then incorporated in Carbopol gel matrix. The anti-psoriatic potential was tested by sequential in vitro (skin permeation and dermal distribution, anti-proliferative effect in HaCaT cells) and in vivo (Draize patch irritation, transepidermal water loss (TEWL) and anti-psoriatic mouse tail studies) experiments.Results: A negligible amount in receptor compartment, yet confined distribution of drugs to epidermal and dermal region of skin was observed in case of SLNs, which is essential for safe and effective anti-psoriatic therapy. Draize patch test and TEWL demonstrated negligible skin irritation and better skin tolerability of SLNs. The in vitro HaCaT cell line study demonstrated that SLNs delayed the abrupt growth of keratinocytes, while in vivo mouse tail model showed that SLNs gel significantly decreased the epidermal thickness and increased melanocyte count in comparison to commercial Daivobet® ointment.Conclusions: The developed SLNs gel is expected to be potential strategies for treatment of psoriasis and other topical diseases.

Anti-Psoriatic Activity of Flavonoids from the Bark of Givotia rottleriformis Griff. Ex Wight.

Givotia rottleriformis has been used in the indigenous systems of medicine for the treatment of inflammatory diseases like rheumatism and psoriasis. In order to evaluate this information, antipsoriatic activity of three flavonoids isolated from the ethanol extract of the bark of Givotia rottleriformis were investigated using in-vitro and in-vivo model, namely Rutin (I), Luteolin-7-O-β-D-Glucuronide (II) and Kaempferol 3-O-[2-O-(6-O-feruloyl)-β-D-glucopyranosyl]-β-D-galactopyranoside (III). The extract was standardized by HPLC using chemical markers. In vitro antiproliferant assay of the ethanol extract and isolated flavonoids were done on HaCaT cell lines. Mouse tail test was used for the evaluation of antipsoriatic activity of ethanol extract (100, 200 and 400 mg/kg b.w.) and bioactive flavonoids (50 mg/kg b.w.) in Swiss albino mice. In the HPLC analysis, 4 flavonoids were identified by comparison with retention time of standard marker viz., Rutin, Quercetin, Kaempferol and Luteolin. Maximum antiproliferant activity was shown by isolated flavonoids II and III (56.50±12.84μg/ml and 76.50±8.60μg/ml). In mouse tail model, a significant reduction in epidermal thickness with respect to control was observed in groups treated with isolated flavonoids II, III and significant orthokeratosis was observed in groups treated with ethanol extract (200 and 400 mg/kg) and isolated flavonoids II, III.

Nano-lipoidal carriers of tretinoin with enhanced percutaneous absorption, photostability, biocompatibility and anti-psoriatic activity

Tretinoin (TRE) is a widely used retinoid for the topical treatment of acne, psoriasis, skin cancer and photoaging. Despite unmatchable efficacy, it is associated with several vexatious side effects like marked skin erythema, peeling and irritation, eventually leading to poor patient compliance. Its photo-instability and high lipophilicity also pose challenges in the development of a suitable topical product. The present study, therefore, aims to develop biocompatible lipid-based nanocarriers of TRE to improve its skin delivery, photostability, biocompatibility and pharmacodynamic efficacy. The TRE-loaded liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanostructured lipidic carriers (NLCs) were prepared and characterized for micromeritics, surface charge, percent drug efficiency and morphology. Bioadhesive hydrogels of the developed systems were also evaluated for rheological characterization, photostability, ex vivo skin permeation and retention employing porcine skin, and anti-psoriatic activity in mouse tail model. Nanoparticulate carriers (SLNs, NLCs) offered enhanced photostability, skin transport and anti-psoriatic activity vis-à-vis the vesicular carriers (liposomes, ethosomes) and the marketed product. However, all the developed nanocarriers were found to be more biocompatible and effective than the marketed product. These encouraging findings can guide in proper selection of topical carriers among diversity of such available carriers systems.

Assessment of Cellular Reactions to Magnesium as Implant Material in Comparison to Titanium and to Glyconate Using the Mouse Tail Model

Nowadays, research in magnesium alloys as a biodegradable implant material has increased. The aim of this study was to examine osteoinductive properties and tissue responses to pure magnesium in comparison to conventional permanent (titanium) and to degradable (glyconate) implant materials. Magnesium wires (0.4 mm in diameter, 10 mm length) were implanted into tail veins of mice and examined after 2, 4, 8, 16 and 32 weeks. Titanium and glyconate as controls were assessed after 2, 4, 8 and 24 weeks. µ-computed tompgraphy, histology and SEM examinations were performed. Magnesium implants showed increasing structural losses over time with fragmentation after an observation period of 32 weeks. Glyconate was fully degraded and titanium remained almost unaffected after 24 weeks. In contrast to some titanium and glyconate implants, first calcium and phosphate precipitations could be observed around magnesium implants after two weeks. However, ossification could not be observed even after 32 weeks, whereas enchondral ossification was found partially in the sourrounding of glyconate and titanium implants after eight weeks. Nevertheless, magnesium implants showed less inflammatory responses and fibrosing properties than the conventional implant materials. Although the assumed osteoinductive properties could not be detected, magnesium appears to be a promising degradable implant material because of the low sensitizing and inflammatory potential.

The role of cyclooxygenase-derived oxidative stress in surgically induced lymphedema in a mouse tail model

Context: Oxidative stress may contribute to lymphedema and subsequent tissue damage. However, the causal role of oxidative stress in lymphedema remains unclear.Objective: We attempted to detect and identify the free radicals formed in lymphedema fluid and assessed the protective mechanisms and effects of specific enzyme inhibitors and natural antioxidants.Materials and methods: To study the level of postsurgical oxidative stress with lymphedema in a mouse tail model, we used an electron spin resonance (ESR) method and an ascorbyl radical’s ESR spectrum as an oxidative stress biomarker. The drug-treatment group received an i.p. injection with indomethacin (2 mg/kg), baicalein (15 mg/kg), MK-886 (3 mg/kg), zileuton (6.25 mg/kg), diphenyleneiodonium (DPI; 1 mg/kg), sulforaphane (30 mg/kg), oryzanol (30 mg/kg) or sesamol (30 mg/kg) once daily for 14 d from the day of operation. All animals were sacrificed on day 14.Results: Administration of indomethacin, sulforaphane, oryzanol and sesamol significantly suppressed both the tail volume (56.9%, 77.8%, 72.2% and 38.1% inhibition, respectively, p < 0.01) and ascorbyl radical signals (31.4%, 54.5%, 79.3% and 57.1% inhibition, respectively, p < 0.01), compared with the control mice. No significant differences were found between any of the baicalein, MK-886, or zileuton groups compared with the control. DPI suppressed the tail volume (25.9% inhibition, p < 0.01) but not the ascorbyl radical signals.Conclusion: This study showed that COX-derived oxidative stress plays a major role in the pathological mechanisms of surgically induced lymphedema. Indomethacin, sulforaphane, oryzanol and sesamol exhibit potent protective properties against surgically induced lymphedema.