Glucocorticoids, sodium transport mediators, and respiratory distress syndrome in preterm infants.

BACKGROUND: Antenatal glucocorticoids (GCs) reduce respiratory distress syndrome (RDS) in preterm infants and are associated with reduced lung liquid content. Our aim was to assess whether airway gene expression of mediators of pulmonary epithelial sodium and liquid absorption, and further, respiratory morbidity, associate with cord blood GC concentrations. METHODS: The study included 64 infants delivered <32 weeks gestation. Cortisol and betamethasone in umbilical cord blood were quantified with liquid chromatography-tandem mass spectrometry. The total GC concentration was calculated. Gene expression of the epithelial sodium channel (ENaC), Na,K-ATPase, and serum- and GC-inducible kinase 1 at <2 h and at 1 day postnatally in nasal epithelial cell samples was quantified with reverse transcription-polymerase chain reaction. The mean oxygen supplementation during the first 72 h was calculated. RESULTS: Concentrations of cord blood betamethasone and total GC were significantly lower in infants with RDS and correlated with mean oxygen supplementation. Expression of αENaC and α1- and ß1Na,K-ATPase at <2 h correlated with betamethasone and total GC concentrations. Expression of Na,K-ATPase was lower in infants with RDS. CONCLUSION: Enhancement of lung liquid absorption via increased expression of sodium transporters may contribute to the beneficial pulmonary effects of antenatal GCs. IMPACT: RDS is related to lower umbilical cord blood GC concentrations and lower airway expression of sodium transporters. In addition to the timing of antenatal GC treatment, resulting concentrations may be of importance in preventing RDS. Induction of sodium transport may be a factor contributing to the pulmonary response to antenatal GCs.

A Prospective, Open-Label Study Evaluating Adjunctive Calcipotriene 0.005%/Betamethasone Dipropionate 0.064% Foam in Psoriasis Patients With Inadequate Response to Biologic Therapy.

OBJECTIVE: To assess the effectiveness and safety of combining calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam with biologic therapies for patients with plaque psoriasis who have not obtained an adequate response with biologic therapy. METHODS: This was a prospective, open-label, single-arm study of patients with chronic plaque-type psoriasis (body surface area [BSA] ≤5%) who were being treated with biologic agents for ≥24 weeks. All patients received once-daily Cal/BD foam for 4 weeks, followed by twice-weekly use on consecutive days for 12 weeks (maintenance regimen). The end points were assessed at weeks 4 and 16, and included the Physician's Global Assessment (PGA), BSA, PGA×BSA, Dermatology Life Quality Index (DLQI), and Treatment Satisfaction Questionnaire for Medication (TSQM)-9. Safety evaluations included assessments of local skin reactions and adverse events (AEs). RESULTS: Enrolled were 25 patients (18 men and 7 women; mean age, 53 ± 11 years). Patients had significant disease activity despite being on stable biologic therapy (median values: BSA, 3%; PGA, 3; PGA×BSA, 8). At weeks 4 and 16 versus baseline, adjunctive therapy with Cal/BD foam significantly improved PGA score (1 vs 1 vs 3; P less than .01), BSA involvement (1% vs 1% vs 3%; P less than .01), and PGA×BSA measure (1 vs 1 vs 8; P less than .01). Most patients achieved treat-to-target criteria for BSA ≤1% and PGA ≤1 at week 4 (both 76%) and week 16 (both 68%) versus 12% and 4%, respectively, at baseline. Quality of life was improved at both weeks 4 and 16, with high treatment satisfaction. Overall, adjunctive Cal/BD foam was safe and well-tolerated, with no serious AEs. CONCLUSIONS: Adjunctive therapy with Cal/BD foam was associated with an improvement of every measure of disease activity in patients with inadequate response to biologics, an effect that was maintained throughout the study. The majority of patients achieved treat-to-target goals. J Drugs Dermatol. 2018;17(8):845-850.

Association of Borage Oil and Betamethasone Dipropionate in Lipid-Core Nanocapsules: Characterization, Photostability and In Vitro Irritation Test.

The association of vegetable products to nanostructured systems has attracted the attention of researchers due to several advantages, such as drug photoprotection, as well as the improvement of the pharmacological and therapeutic activities because of synergistic action, which can provide their topical application. In this work, lipid-core nanocapsules containing borage oil as oil core and betamethasone dipropionate were developed, and nanocapsules without the drug were prepared for comparison. The suspensions were characterized in relation to mean particle size, zeta potential, pH, drug content, and encapsulation efficiency. A photodegradation study was carried out and the in vitro release profile as well as the irritation potential of the drug after nanoencapsulation were also evaluated. In addition, the antiproliferative activity of the free borage oil as well as loaded in nanocapsules was studied. Lipid-core nanocapsules showed nanometric mean size (185-210 nm); polydispersity index below 0.10; negative zeta potential and pH slightly acid (6.0-6.2). Moreover, the drug content was close to theoretical concentration (0.50 +/- 0.03 mg/ml of betamethasone), and the encapsulation efficiency was approximately 100%. The study of the antiproliferative activity of borage oil showed ability to reduce cell growth of Allium cepa. The nanoencapsulation of betamethasone dipropionate provided greater protection against UVC light and decreased the irritation potential of the drug. The release profile of betamethasone dipropionate from nanocapsules followed monoexponential model.

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.

Skin penetration behaviour of liposomes as a function of their composition.

Deformable liposomes have been developed and evaluated as a novel topical and transdermal delivery system. Their mechanism of drug transport into and through the skin has been investigated but remains a much debated question. The present study concerns ex vivo diffusion experiments using pig ear skin in order to explain the penetration mechanism of classical and deformable liposomes. Classical and deformable vesicles containing betamethasone in the aqueous compartment through the use of cyclodextrin inclusion complexes were compared to vesicles encapsulating betamethasone in their lipid bilayer. Deformable liposomes contained sodium deoxycholate as the edge activator. Liposomes were characterised by their diameter, encapsulation efficiency, deformability, stability (in terms of change in diameter) and release of encapsulated drug. Ex vivo diffusion studies using Franz diffusion cells were performed. Confocal microscopy was performed to visualise the penetration of fluorescently labelled liposomes into the skin. This study showed that liposomes do not stay intact when they penetrate the deepest layers of the skin. Betamethasone is released from the vesicles after which free drug molecules can diffuse through the stratum corneum and partition into the viable skin tissue.

New approaches to assess topical corticosteroid bioequivalence: pharmacokinetic evaluation.

An ideal method for measuring the bioavailability of topical corticosteroids should be simple, accurate, and adaptable to a variety of settings and should not require extensive special training to perform. Drug uptake into the stratum corneum, measured by tapestripping, is correlated with the pharmacodynamic response of skin blanching, observed in the vasoconstrictor assay. Differences in stratum corneum drug uptake can be objectively quantitated as a function of time, occlusion, dose applied, and vehicle. Tapestripping measurements are reproducible within individual subjects, but large interindividual variabilities may exist. The chromameter, a new technology, objectively quantitates color numerically and can be used to measure skin blanching as part of the pharmacodynamic response to topical corticosteroids. The chromameter offers an easy, objective method with which to quantitate the pharmacodynamic response of topical corticosteroids. Both methods allow a more mechanistic approach than currently used methods to investigate topical drug pharmacokinetics and pharmacodynamics.

Topical corticosteroids: quality control considerations.

A simple procedure is developed, which can be used as a quality control test. The method utilizes commercially available diffusion cell assembly, synthetic membrane, and an appropriate receptor phase. The amount of drug released over time is determined using an HPLC method. From this, the drug release rate, flux, microgram/cm2/min0.5 is calculated. This drug release rate can serve as a good quality control test to assure batch-to-batch uniformity.