Dithranol-loaded nanostructured lipid carrier-based gel ameliorate psoriasis in imiquimod-induced mice psoriatic plaque model.

OBJECTIVE: The aim of this study was to formulate nanostructured lipid carriers (NLCs) of dithranol-loaded in gel for ease of application and to evaluate its anti-psoriatic efficacy vis-a-vis conventional ointment formulation. SIGNIFICANCE: This study will provide an insight about the use of nanocarriers, esp. NLCs loaded with dithranol for the effective treatment of psoriasis. METHODS: Dithranol-loaded NLCs were prepared by hot melt homogenization method and characterized for particle size and percentage entrapment efficiency. The optimized NLCs were loaded into gel and evaluated for drug release, spreadability, rheological behavior, and staining. Anti-psoriatic efficacy of the NLC gel was evaluated in imiquimod (IMQ) induced psoriatic plaque model in comparison with prepared conventional ointment formulation (1.15% w/w dithranol). RESULTS: NLCs were prepared with particle size below 300 nm, polydispersity index (PDI) below 0.3 and percentage entrapment efficiency of ∼100%. The prepared NLC gel was then compared with the ointment for drug release, staining property, and efficacy. Topical application of dithranol-loaded NLC gel on IMQ-induced psoriatic plaque model reduced the symptoms of psoriasis assessed by both Psoriasis area severity index (PASI) scoring and enzyme-linked immunosorbent assay. There was a significant reduction in disease severity and cytokines like Interleukins-17, 22, 23 and Tumor necrosis factor-α by the developed system in comparison to the negative control. CONCLUSIONS: To conclude dithranol-loaded NLCs in gel base was efficacious in management of psoriasis at the same drug concentration and also offer less cloth staining to that of the ointment product.

Making colourful sense of Raman images of single cells.

In order to understand biological systems it is important to gain pertinent information on the spatial localisation of chemicals within cells. With the relatively recent advent of high-resolution chemical imaging this is being realised and one rapidly developing area of research is the Raman mapping of single cells, an approach whose success has vast potential for numerous areas of biomedical research. However, there is a danger of undermining the potential routine use of Raman mapping due to a lack of consistency and transparency in the way false-shaded Raman images are constructed. In this study we demonstrate, through the use of simulated data and real Raman maps of single human keratinocyte (HaCaT) cells, how changes in the application of colour shading can dramatically alter the final Raman images. In order to avoid ambiguity and potential subjectivity in image interpretation we suggest that data distribution plots are used to aid shading approaches and that extreme care is taken to use the most appropriate false-shading for the biomedical question under investigation.

Dithranol-loaded lipid-core nanocapsules improve the photostability and reduce the in vitro irritation potential of this drug.

Dithranol is a very effective drug for the topical treatment of psoriasis. However, it has some adverse effects such as irritation and stain in the skin that make its application and patient adherence to treatment difficult. The aims of this work were to prepare and characterize dithranol-loaded nanocapsules as well as to evaluate the photostability and the irritation potential of these nanocarriers. Lipid-core nanocapsules containing dithranol (0.5 mg/mL) were prepared by interfacial deposition of preformed polymer. EDTA (0.05%) or ascorbic acid (0.02%) was used as antioxidants. After preparation, dithranol-loaded lipid-core nanocapsules showed satisfactory characteristics: drug content close to the theoretical concentration, encapsulation efficiency of about 100%, nanometric mean size (230-250 nm), polydispersity index below 0.25, negative zeta potential, and pH values from 4.3 to 5.6. In the photodegradation study against UVA light, we observed a higher stability of the dithranol-loaded lipid-core nanocapsules comparing to the solution containing the free drug (half-life times around 4 and 1h for the dithranol-loaded lipid-core nanocapsules and free drug solution containing EDTA, respectively; half-life times around 17 and 7h for the dithranol-loaded lipid-core nanocapsules and free drug solution containing ascorbic acid, respectively). Irritation test by HET-CAM method was conducted to evaluate the safety of the formulations. From the results it was found that the nanoencapsulation of the drug decreased its toxicity compared to the effects observed for the free drug.

Hyperbranched dendritic nano-carriers for topical delivery of dithranol.

The purpose of the current investigation was to explore the potential of polypropylene imine (PPI) dendrimers to deliver dithranol (DIT) topically and to evaluate its encapsulation, permeation and skin irritation potential. PPI (5.0 generation, 5.0 G) dendrimers and DIT-loaded PPI (DIT-PPI) were prepared and characterized by spectroscopy and transmission electron microscopy. DIT encapsulation, in vitro skin permeation study, skin irritation studies, fluorescent studies and tape stripping studies were performed. Loading of DIT was found to be pH dependent with maximum encapsulation at acidic pH (1.0 ± 0.02, 17.2 ± 0.56 and 57.1 ± 1.32% at 7.4, 5.5 and 1.2 pH, respectively). DIT-PPI showed significantly enhanced permeation rate constant and lesser skin irritation (11.61 ± 1.80 µg/cm(2)/h and 1.0, respectively) when compared with the plain DIT solution (2.72 ± 0.31 µg/cm(2)/h and 2.3, respectively). Skin separation studies and confocal laser scanning microscope images showed that the dye-loaded dendrimers exhibits deposition of dye in pilosebaceous compartment. These studies demonstrate that PPI can be exploited to improve the topical bioavailability of the molecules in a controlled pattern. The enhanced accumulation of DIT via dendrimer carrier within the skin might help optimize targeting of this drug to the epidermal and dermal sites, thus creating new opportunities for well-controlled, modern topical application of DIT for the treatment of psoriasis.

Therapy of psoriasis in childhood and adolescence - a German expert consensus.

Psoriasis of childhood shows an annual prevalence of 0.71 % and accordingly has to be regarded as a frequent chronic inflammatory skin disorder of this age. The impact on the quality of life as well as development of the afflicted children and their parents is evident. On the other side, therapy is demanding with regard to the specific juvenile metabolism, physical development and skin penetration of topical drugs. Long-term treatment at an early age has to be critically judged regarding the chronicity of the disease. Topical corticosteroids, alternatively dithranol may be used first-line, followed by vitamin D derivatives. A combination with UV-light, preferably UV-B, has to be decided on an individual basis. Systemic treatment may be initiated in recalcitrant disease with methotrexate and cyclosporine where long-term experience is available from juvenile rheumatology and transplantation medicine. Alternatively fumaric acid esters or retinoids are available. Rehabilitation procedures will help the children and their parents to cope with the disease and its treatment. The different treatment options are presented here as a German expert consensus, as clinical studies are hardly available and only a few therapeutics are licensed for this age. In any case the therapy has to be individually planned and decided together with the patients and their parents to gain maximal safety, comfort and success.

Topical delivery of a naproxen-dithranol co-drug: in vitro skin penetration, permeation, and staining.

PURPOSE: This work probed the topical delivery and skin-staining properties of a novel co-drug, naproxyl-dithranol (Nap-DTH), which comprises anti-inflammatory (naproxen) and anti-proliferative (dithranol) moieties. METHOD: Freshly excised, full-thickness porcine ear skin was dosed with saturated solutions of the compounds. After 24 h, the skin was recovered and used to prepare comparative depth profiles by the tape-stripping technique and to examine the extent of skin staining. RESULTS: Depth profiles showed that Nap-DTH led to a 5-fold increase in drug retention in the skin compared to dithranol. The application of Nap-DTH also demonstrated improved stability, resulting in lower levels of dithranol degradation products in the skin. Furthermore, significantly less naproxen from hydrolysed Nap-DTH permeated into the receptor phase compared to naproxen when applied alone (0.08 ± 0.03 nmol cm(-)² and 180 ± 60 nmol cm(-)², respectively). Moreover, the reduced staining of the skin was very apparent for Nap-DTH compared to dithranol. CONCLUSIONS: Topical delivery of Nap-DTH not only improves the delivery of naproxen and dithranol, but also reduces unwanted effects of the parent moieties, in particular the skin staining, which is a major issue concerning the use of dithranol.

Hydrophilic silica aerogels as dermal drug delivery systems--dithranol as a model drug.

A special class of porous silica materials, silica aerogels, was recently shown to be a potential candidate for oral drug delivery systems. It was demonstrated, that stability of drugs and their dissolution rate can essentially be improved through the adsorption on to these materials. In this work, drug loaded silica aerogels are firstly applied as dermal drug delivery systems. Dithranol is used as a representative drug since there is a need to enhance its dermal availability. The unstable and nearly water-insoluble drug exhibits a poor penetration. Release of dithranol from aerogels into various semi-solid formulations and its dissolution as well as the release and penetration into artificial membranes were investigated by Fourier-transform infrared attenuated total reflection (FTIR-ATR) spectroscopy. Two model membranes (one hydrophilic and one lipophilic) were applied. Several formulations were tested and the most promising one was used in order to study the penetration of dithranol into human stratum corneum (SC). Dithranol adsorbed on hydrophilic silica aerogels exhibited superior penetration behaviour compared to that of the standard ointment (dithranol in white soft paraffin).

Drug penetration as studied by noninvasive methods: fourier transform infrared-attenuated total reflection, fourier transform infrared, and ultraviolet photoacoustic spectroscopy.

The penetration of the drugs dithranol and methoxsalen from semisolid Vaseline formulation into an artificial dodecanol-collodion membrane was followed by three spectroscopic methods; they are, step-scan Fourier transform infrared (FTIR) photoacoustic spectroscopy (PAS) with phase modulation, FTIR-attenuated total reflection (FTIR-ATR), and ultraviolet (UV) PAS. The uptake of the drug in the membrane was quantified by monitoring the dependence of an appropriate drug band on the penetration time. The PAS experiments were carried out with various modulation frequencies for generating various sampling depths. Based on Fick's second law, the diffusion coefficient was derived by numerical fitting of the experimental data. It appears that the diffusion coefficient for the drug in the membrane depends on the distance. The comparative studies demonstrate that FTIR-ATR is favored for permeation studies, whereas the PAS techniques are capable of providing the drug penetration profile in the membrane. Thus, extended experimental data are available for new insight into the penetration process. However, because of the photacoustic cells at hand, PAS is only suitable for in vitro studies.

Enhancement of the penetration of dithranol and increase of effect of dithranol on the skin by liposomes.

An assessment was made in healthy skin of dithranol erythema caused by a 10-min occlusive application of 0.5% dithranol (CAS 1143-38-0) in liposomal gel (Natipide II) with and without the addition of 3% salicylic acid, and of 0.5% dithranol in vaseline and in a removable standard ointment base, both with 3% salicylic acid. Both liposomal preparations led to a significant potentiation of the dithranol erythema. The results indicate a strong promotion of the penetration of dithranol by the liposomal gel.

[Correlations between the properties and effects of clinical therapy using textile material with antipsoriatic action]. / Korelacja wlasciwosci i efektów terapii klinicznej materialu tekstylnego o dzialaniu przeciwluszczycowym.

The aim of the study was to design a textile material as a carrier for dermatological drugs. Cotton fabric was chosen for experimentation to be a fibrous support for the system. Additional components were a drug carrier in form of synthetic hydrogel impregnation (partially crosslinked poly(acrylic acid) and a bioactive agent dithranol) dispersed within the gel. The rate of release of the drug from the fibrous system was measured in aqueous media and depended on the concentration of dithranol. The structure and physical properties of the material were designed and controlled in order to ensure the optimal contact with the skin. Clinical studies were carried out with psoriatic patients. The results of the treatment with the textile material containing dithranol were presented using a computer optimalization method. In conclusion it was asserted that this type of textile-based medical device is effective and in many respects more convenient and less troublesome alternative in the treatment of psoriasis as compared to conventional treatments with dithranol suspended in ointments and creams.

[Promoting penetration of locally applied substances by urea]. / Penetrationsförderung lokal applizierter Wirkstoffe durch Harnstoff.

These studies indicate that urea alters the physical and chemical properties of keratin so that permeation of monosubstances in urea-altered keratin is increased. The permeation kinetics of keratin can be influenced by splitting and/or altering the surface structure of keratin, which enhances the permeation of steroids, dithranol, and other substances. The regulation of permeation kinetics in the horny layer also applies to urea. The permeation of urea in and through the horny layer can lead to an alteration in the binding capacity within this layer (reservoir capacity). Thus, the penetration of substances such as oxiconazol through the horny layer can be decreased and their retention time increased. Nevertheless, urea is not always the stimulator of permeation processes.