Betamethasone valerate 0.1% / Clioquinol 3% ointment

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease without effective treatment. The utilization of all trans-retinoic acid (TRA) and betamethasone (BT) for the treatment of psoriasis is still facing difficulties, due to their relatively poor stability, limited skin permeation, and systemic side effects. Flexible liposomes are excellent in deeper skin permeation and reducing the side effects of drugs, which is promising for effective treatment of skin disorders. This work aimed to establish dual-loaded flexible liposomal gel for enhanced therapeutic efficiency of psoriasis based on TRA and BT. RESULTS: Flexible liposomes co-loaded with TRA and BT were successfully prepared in our study. The characterization examination revealed that flexible liposomes featured nano-sized particles (around 70 nm), high drug encapsulation efficiency (> 98%) and sustained drug release behaviors. Flexible liposomes remarkably increased the drug skin permeation and retention as compared with free drugs. Results on HaCaT cells suggested that flexible liposomes were nontoxic, and its cellular uptake has a time-dependent manner. In vivo studies suggested the topical application of TRA and BT dual-loaded liposomal gel had the best ability to reduce the thickness of epidermal and the level of cytokines (TNF-α and IL-6), largely alleviating the symptoms of psoriasis. CONCLUSIONS: Flexible liposomal gel dual-loaded with TRA and BT exerted a synergistic effect, which is a promising topical therapeutic for the treatment of psoriasis.

Abstract licence: CC BY

Despite decades of research into the pathology mechanisms of Parkinson's disease (PD), disease-modifying therapy of PD is scarce. Thus, searching for new drugs or more effective neurosurgical treatments has elicited much interest. Clioquinol (CQ) has been shown to have therapeutic benefits in rodent models of neurodegenerative disorders. However, it's neuroprotective role and mechanisms in PD primate models and PD patients, especially in the advanced stages, are not fully understood. Furthermore, issues such as spontaneous recovery of motor function and high symptom variability in different monkeys after the same toxic protocol, has not been resolved before the present study. In this study, we designed a chronic and long-term progressive protocol to generate a stabilized PD monkey model showed with classic motor and non-motor deficits, followed by treatment analysis of CQ. We found that CQ could remarkably improve the motor and non-motor deficits, which were based on the reduction of iron content and ROS level in the SN and further improvement in pathology. Meanwhile, we also showed that ferroptosis was probably involved in the pathogenesis of PD. In addition, the study shows a positive effect of CQ on AKT/mTOR survival pathway and a blocking effect on p53 medicated cell death

Abstract licence: CC BY

High-dose betamethasone and dexamethasone are standard of care treatments for women at risk of preterm delivery to improve neonatal respiratory and mortality outcomes. The dose in current use has never been evaluated to minimize exposures while assuring efficacy. We report the pharmacokinetics and pharmacodynamics (PDs) of oral and intramuscular treatments with single 6 mg doses of dexamethasone phosphate, betamethasone phosphate, or a 1:1 mixture of betamethasone phosphate and betamethasone acetate in reproductive age South Asian women. Intramuscular or oral betamethasone has a terminal half-life of 11 hours, about twice as long as the 5.5 hours for oral and intramuscular dexamethasone. The 1:1 mixture of betamethasone phosphate and betamethasone acetate shows an immediate release of betamethasone followed by a slow release where plasma betamethasone can be measured out to 14 days after the single dose administration, likely from a depo formed at the injection site by the acetate. PD responses were: increased glucose, suppressed cortisol, increased neutrophils, and suppressed basophils, CD3CD4 and CD3CD8 lymphocytes. PD responses were comparable for betamethasone and dexamethasone, but with longer times to return to baseline for betamethasone. The 1:1 mixture of betamethasone phosphate and betamethasone acetate caused much longer adrenal suppression because of the slow release. These results will guide the development of better treatment strategies to minimize fetal and maternal drug exposures for women at risk of preterm delivery.

Abstract licence: CC BY