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Heliyon Mar 2019Dithranol is one of the important topical agents for the treatment of psoriasis, a chronic inflammatory skin disease with aberrant differentiation of keratinocytes....
Dithranol is one of the important topical agents for the treatment of psoriasis, a chronic inflammatory skin disease with aberrant differentiation of keratinocytes. However, its application is troublesome and inconvenient because of its associated side effects, including staining, burning sensation, irritation, and necrotizing effect on the diseased cells as well as on the normal cells. The purpose of the current investigation was to explore the potential of poly(amido) amine (PAMAM) dendrimers in the topical delivery of dithranol through a novel microsponge based gel. Generation-4 (G4) dendrimers were incorporated into the microsponge based gel formulation by quasi-emulsion solvent diffusion method with varying concentration of polymers, and evaluated for the morphology of the formulation, encapsulation efficiency and skin irritation potential. Percentage yield of the formulation was found to be 66.28%, whereas encapsulation efficiency was ranged between 71.33% to 49.21%, and an average particle size was ranged between 28 ± 1.12 μm to 130 ± 1.01 μm. Surface morphology of developed microsponge was confirmed by scanning electron microscopy, revealed micro-porous nature. The optimized microsponge formulation was found to be stable and recorded non-irritant during cutaneous application of the experimental animals. Further, the pharmacokinetic outcomes of study were showed prolong penetration of the drug through the skin, equivalent to the marketed formulation of dithranol. Therefore, it could be conferred that the microsponge formulation of the PAMAM entrapped dithranol can produce prolonged efficacy without producing toxicities to the skin, and thus can effectively be projected in the treatment of diseases like psoriasis.
PubMed: 30957038
DOI: 10.1016/j.heliyon.2019.e01343 -
ELife Jun 2020Despite the introduction of biologics, topical dithranol (anthralin) has remained one of the most effective anti-psoriatic agents. Serial biopsies from human psoriatic...
Despite the introduction of biologics, topical dithranol (anthralin) has remained one of the most effective anti-psoriatic agents. Serial biopsies from human psoriatic lesions and both the c-Jun/JunB and imiquimod psoriasis mouse model allowed us to study the therapeutic mechanism of this drug. Top differentially expressed genes in the early response to dithranol belonged to keratinocyte and epidermal differentiation pathways and IL-1 family members (i.e. but not elements of the IL-17/IL-23 axis. In human psoriatic response to dithranol, rapid decrease in expression of keratinocyte differentiation regulators (e.g. involucrin, and ), antimicrobial peptides (e.g. ß-defensins like S100 proteins like ), chemotactic factors for neutrophils (e.g. ) and neutrophilic infiltration was followed with much delay by reduction in T cell infiltration. Targeting keratinocytes rather than immune cells may be an alternative approach in particular for topical anti-psoriatic treatment, an area with high need for new drugs.
Topics: Animals; Anthralin; Chemokines, CXC; Dermatologic Agents; Interleukin-1; Keratinocytes; Mice; Neutrophils; Pore Forming Cytotoxic Proteins; Psoriasis; Serpins; Signal Transduction; Skin
PubMed: 32484435
DOI: 10.7554/eLife.56991 -
Anais Brasileiros de Dermatologia 2021
Randomized Controlled Trial
Topics: Administration, Topical; Alopecia Areata; Anthralin; Cyclopropanes; Humans
PubMed: 33849753
DOI: 10.1016/j.abd.2020.06.018 -
World Journal of Plastic Surgery Mar 2022A 16-year-old female with psoriasis presented to our Plastic Surgery Department with a significant chemical burn to the neck, upper torso and left cheek (TBSA 6%). She...
A 16-year-old female with psoriasis presented to our Plastic Surgery Department with a significant chemical burn to the neck, upper torso and left cheek (TBSA 6%). She applied a concoction of cream prescribed by her dermatologist in her native country, Poland when she returned to the United Kingdom. A few hours after application she developed a burn with pH of 5. A review of the cream revealed a mixture of 19% dithranol and 5% salicylic acid. This combination is recognized for managing psoriasis, however the strength of dithranol in the combination given is of a high concentration (normally <3%). This alone can cause a burn to the skin if left for a prolonged period of time. Salicylic acid is an enhancer which augments the stability of dithranol and increases its penetration and efficacy. The concentration of 5% is also on the higher end. Our patient was admitted for pain relief and further irrigation till normalization of the pH which was achieved after 3 days. A worrying aspect in our patients' case is that she was given the cream to commence at home. High concentration preparation is normally commenced in a controlled setting under medical supervision.
PubMed: 35592224
DOI: 10.52547/wjps.11.1.138 -
NPJ Vaccines Jun 2023
PubMed: 37349361
DOI: 10.1038/s41541-023-00689-9 -
Molecules (Basel, Switzerland) Jan 20231,8-dihydroxy-9-anthrone are tricyclic compounds with a ketone group in the middle ring and two hydroxyl groups substituted in the side-aromatic rings what results in...
1,8-dihydroxy-9-anthrone are tricyclic compounds with a ketone group in the middle ring and two hydroxyl groups substituted in the side-aromatic rings what results in formation of two intramolecular hydrogen bonds in which the oxygen atom from the ketone group is the proton acceptor. 1,8-dihydroxy-9-anthrones in which intramolecular proton transfer between C10 and CO in the middle ring occurs, can exist in a tautomeric keto-enol equilibrium. For anthralin, the most important representative of this group, this equilibrium has been studied previously, but it has not been studied for its derivatives. Substituents in the middle ring change the geometry of 1,8-dihydroxy-9-anthrones so they are also expected to affect the keto-enol equilibrium. It is also important to study the effect of intramolecular hydrogen bonds on the structure of both tautomeric forms. It was found that the nature of the substituent in the middle ring could affect the antioxidant properties of the investigated compound.
Topics: Anthralin; Protons; Electrons; Anthracenes; Alcohols; Ketones
PubMed: 36615539
DOI: 10.3390/molecules28010344 -
Cureus May 2024Background Psoriasis is a papulosquamous disease with variable morphology, distribution, severity, and course. Chronic plaque psoriasis, or psoriasis vulgaris, is the...
Background Psoriasis is a papulosquamous disease with variable morphology, distribution, severity, and course. Chronic plaque psoriasis, or psoriasis vulgaris, is the most common form of psoriasis. Present available preparations for mild to moderate chronic plaque psoriasis for topical use are local corticosteroids, coal tar, dithranol, tazarotene, calcipotriol, tapinarof, and calcineurin inhibitors. However, every preparation has its disadvantages. Calcipotriol, an active form of vitamin D, is available in topical form for dermatological use. Chronic plaque psoriasis is the chief medical use of calcipotriol for mild to moderate form. Methotrexate has dramatic results in psoriasis when used systemically. Now, topical formulation is being advocated in localized psoriasis, which is not associated with the side effects of the systemic form. Therefore, this study aimed to compare the effectiveness of topical calcipotriol and topical methotrexate on the basis of the psoriasis area severity index (PASI) in patients of chronic plaque psoriasis and compare their safety in terms of adverse effects. Methodology The total number of patients included in the study was 60. They were divided into two groups, with 30 patients each. One group was prescribed ointment calcipotriol 0.005% twice daily local application (Group C). The other group was prescribed methotrexate gel 1% twice daily local application (Group M). The patients were followed up on the fourth and eighth weeks, and at each time, thorough clinical examinations were conducted for all patients. The PASI score was calculated in each patient every time. Safety was assessed by biochemical parameters, and tolerability was assessed by the incidence of adverse effects. All the patients included in the study were investigated at baseline, fourth week, and eighth week. The data collected were transferred to a master chart and analyzed. Results For the patients in group C, the mean PASI score at 0 week was 5.93 ± 2.62, while at four weeks, the mean PASI score declined to 1.67 ± 1.13, and at eight weeks, the mean PASI score further declined to 0.67 ± 0.68. For the patients in group M, the mean PASI score at 0 week was 5.91 ± 2.22, while at four weeks, the mean PASI score declined to 1.91 ± 1.11, and at eight weeks, the mean PASI score further declined to 0.89 ± 0.72. Furthermore, there was no significant difference in the mean PASI score at various time points when compared between the two groups (p-value = 0.761, 0.296, 0.079, respectively). Thus, both drugs seem to be effective in treating mild- to moderate-grade chronic plaque psoriasis. Most of the patients in both groups showed marked clearance of the lesions. However, there were six patients in the calcipotriol group showing complete clearance of the lesions having mild-degree plaque psoriasis, as compared to three patients in the methotrexate group. In the present study, based on the comparison of safety and tolerability, four out of 30 patients (13.3%) in the calcipotriol group suffered skin irritation, whereas six out of 30 patients (20%) in the methotrexate group complained of a burning sensation. The adverse effects seen in the patients were transient and mild. Conclusion Topical calcipotriol and methotrexate were effective in reducing lesions in patients with chronic mild to moderate plaque psoriasis. Both drugs were well tolerated with mild and transient adverse effects and did not alter hematological and biochemical parameters.
PubMed: 38854231
DOI: 10.7759/cureus.59878 -
Skin Pharmacology and Physiology 2016Alterations of the skin microvasculature are known to play an important role in the development and maintenance of psoriatic skin lesions. In this study, we investigated... (Clinical Trial)
Clinical Trial
Alterations of the skin microvasculature are known to play an important role in the development and maintenance of psoriatic skin lesions. In this study, we investigated lesional skin in 11 psoriatic patients during a modified Goeckerman treatment using reflectance confocal microscopy (RCM) to study the relationship between clinical clearance and histological normalization of psoriatic skin and the significance of histological abnormalities on the course of disease. The treatment regimen resulted in a significant reduction of the Psoriasis Area and Severity Index (PASI) as well as capillary and papillary diameters (p < 0.0001). The capillary and papillary diameters were still enlarged when compared to those in normal skin (p < 0.001). Capillary and papillary diameters correlated with each other prior to and after treatment (correlation coefficient = 0.63 and 0.64, p = 0.01 and 0.002, respectively) but not with the PASI. Capillary and papillary diameters after treatment and percentage reduction of the PASI during treatment seemed to be better predictors for the clinical course of relapse than the PASI after treatment. These findings make the subclinical changes of psoriatic skin vessels and dermal papillae a legitimate target for treatment. Further investigations of a large group of patients are needed to evaluate the potential of RCM findings as successor of the PASI in the monitoring of psoriasis.
Topics: Anthralin; Capillaries; Castor Oil; Coal Tar; Female; Humans; Male; Microscopy, Confocal; Middle Aged; Pilot Projects; Psoriasis; Salicylic Acid; Salts; Severity of Illness Index; Skin; Ultraviolet Therapy
PubMed: 26841099
DOI: 10.1159/000443211 -
Cell and Tissue Research Dec 2020Inflammation of the cutaneous orofacial tissue can lead to a prolonged alteration of neuronal and nonneuronal cellular functions in trigeminal nociceptive pathways. In...
Inflammation of the cutaneous orofacial tissue can lead to a prolonged alteration of neuronal and nonneuronal cellular functions in trigeminal nociceptive pathways. In this study, we investigated the effects of experimentally induced skin inflammation by dithranol (anthralin) on macrophage activation in the rat trigeminal ganglion. Tissue localization and protein expression levels of ionized calcium-binding adaptor molecule 1 (Iba1), a macrophage/microglia-specific marker, and proliferation/mitotic marker antigen identified by the monoclonal antibody Ki67 (Ki67), were quantitatively analyzed using immunohistochemistry and western blots in control, dithranol-treated, dithranol- and corticosteroid-treated, and corticosteroid-treated trigeminal ganglia. Chronic orofacial dithranol treatment elicited a strong pro-inflammatory effect in the ipsilateral trigeminal ganglion. Indeed, daily dithranol treatment of the orofacial skin for 3-5 days increased the number of macrophages and Iba1 protein expression in the maxillary subregion of the ipsilateral ganglion. In the affected ganglia, none of the Iba1-positive cells expressed Ki67. This absence of mitotically active cells suggested that the accumulation of macrophages in the ganglion was not the result of resident microglia proliferation but rather the extravasation of hematogenous monocytes from the periphery. Subsequently, when a 5-day-long anti-inflammatory corticosteroid therapy was employed on the previously dithranol-treated orofacial skin, Iba1 immunoreactivity was substantially reduced in the ipsilateral ganglion. Collectively, our findings indicate that both peripheral inflammation and subsequent anti-inflammatory therapy affect macrophage activity and thus interfere with the functioning of the affected sensory ganglion neurons.
Topics: Adrenal Cortex Hormones; Animals; Inflammation; Macrophages; Male; Rats; Skin; Trigeminal Ganglion
PubMed: 32696216
DOI: 10.1007/s00441-020-03244-3 -
Chemical Science Jan 2015A novel technique, termed matrix coating assisted by an electric field (MCAEF), for enhancing tissue imaging by matrix-assisted laser desorption/ionization mass...
A novel technique, termed matrix coating assisted by an electric field (MCAEF), for enhancing tissue imaging by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was developed in this study. In this technique a static and uniform electric field is applied to sliced tissue sections during matrix spray-coating, resulting in the enrichment of positively or negatively chargeable analytes in the MALDI matrix layer. Experimental results show that MCAEF not only increased the sensitivity of lipid and protein detection across the board in the subsequent MALDI-MS analyses, but also resulted in successful imaging of a larger number of analytes. MALDI imaging enhancement with MCAEF was observed for various tissues (rat liver, rat brain, and porcine adrenal gland) and with different MALDI matrices (, quercetin, 2-mercaptobenzothiazole, dithranol, 9-aminoacridine, and sinapinic acid) and the sensitivity increases were independent of the solvent compositions and pH values of the matrix solutions. Taking rat brain as an example, MCAEF led to the on-tissue detection and imaging of 648 identified lipids by combining positive and negative ion detection by MALDI-Fourier transform ion cyclotron resonance MS and with quercetin as the matrix, as compared to only 344 lipids without MCAEF. For protein imaging, up to 232 protein signals were successfully detected in rat brain tissue sections by MALDI-time-of-flight MS within a mass range of 3500 to 37 000 Da, as compared to 119 without MCAEF. MCAEF also enabled the detection of higher molecular-weight proteins. These results demonstrate the advantages of MCAEF for overall performance improvements in MALDI imaging and we believe that this technique has the potential to become a standard practice for MALDI tissue imaging.
PubMed: 28706636
DOI: 10.1039/c4sc01850h