Desonide Nanoemulsion Gel for Transdermal Absorption Drug Delivery: Pharmacodynamic and Safety Evaluation.

BACKGROUND: When administered transdermally, desonide is ineffective due to its poor solubility. As a new transdermal delivery system, nanoemulsion gel has demonstrated significant advantages for drug delivery over conventional formulations. We have established desonide nanoemulsion gel (DES NE gel) for better transdermal absorption, but its efficacy and safety still need to be evaluated. This study aims to provide additional evidence demonstrating the improved pharmacodynamics and safety of transdermal delivery of Desonide via nanoemulsion gel. METHODS: Pharmacodynamics and safety of Desonide nanoemulsion gel were evaluated using Desonate ® as the reference formulation. To assess the difference in curative effect between DES NE gel and Desonate® and to ensure safety, atopic dermatitis (AD) models in KM mice were developed using 2,4-dinitrofluorobenzene (DNFB). The degree of ear swelling, ear mass difference, thymus, spleen index, and HE conventional pathology of mice were used as pharmacodynamic evaluation indexes, and the irritation was predicted by the New Zealand rabbit epidermal stimulation assay. RESULTS: Nanoemulsion gels may facilitate transdermal penetration of drugs by influencing the skin condition. Medium and high doses of DES NE gel significantly ameliorated the inflammation and swelling of the ear caused by dermatitis/eczema in mice. In addition, compared with DES gel, skin irritation extent did not increase. CONCLUSION: Nanoemulsion gel can be applied to improve the efficacy of drugs with low potency or poor solubility. DES NE gel provides a higher transdermal potential than other delivery systems. In this study, it was found that nanoemulsion gel is a promising percutaneous carrier of DES. DES NE-GEL has a significant curative effect on dermatitis/eczema in a mouse model and is expected to provide a new, efficient, and low toxic preparation for clinical treatment of dermatitis/eczema through the percutaneous system.

Effect of structural alterations on the biotransformation rate of glucocorticosteroids in rat and human liver.

The effect of structural alterations on the biotransformation rate of glucocorticosteroids (GCS) by rat- and human-liver 9000 g supernatant fraction was studied. Insertion of a 16 alpha-hydroxy group in the prednisolone molecule (16 alpha-hydroxyprednisolone) was found to decrease the rate of biotransformation. Substitution of the 16 alpha,17 alpha-hydroxy groups with a symmetric acetal (in, for example, desonide) or especially a non-symmetric acetal (in, for example, budesonide), enhanced the biotransformation rate several-fold, particularly in human liver. Differences in the rates of metabolism in rat and human liver were observed. Hydrogenation of the 1,2-double bond in prednisolone and budesonide (hydrocortisone and 1,2-dihydrobudesonide) enhanced the biotransformation rate nine-fold in rat liver but only two-fold in human liver. Fluorination of the steroid nucleus in 6 alpha- and 9 alpha-positions enhanced the biotransformation rate several-fold in human liver, but in rat liver fluorination marginally decreased the rate of biotransformation. These in vitro results correlate well with available data on the first-pass liver metabolism of the studied GCS. This indicates that in vitro data can be useful in predicting oral bioavailability of GCS.