P.1.l.026 - Chronic magnesium supplementation increases hippocampal neurogenesis and decreases proliferation in myocardium in ACTH-treated rats

Abstract

The aim of this study was to compare the efficacy of different approaches for enhancement of dermal availability of the highly lipophilic antifungal model drug – sertaconazole nitrate (SN). For this purpose, a physical penetration enhancer – dissolving microneedles (MNs) was fabricated by filling moulds with liquid formulation based on polyvinylpyrrolidone and loaded with SN. Dissolving MNs were characterised regarding their morphological and mechanical characteristics. A penetration enhancement efficacy of MNs was evaluated in vitro using porcine ear skin in parallel with the efficacy of formerly developed chemical penetration enhancer – biocompatible microemulsion (ME) formulation. Moreover, an ability of solid silicon MNs to significantly improve delivery of SN from ME into the skin has also been investigated. The obtained results showed that dissolving MNs had satisfying morphological properties and mechanical strength. This type of MNs provided comparable drug deposition in the skin as ME formulation, but also revealed an indication of percutaneous absorption of a portion of the administered drug dose. However, the penetration/permeation study results were largely influenced by experimental setup and dosing regimen. Although solid silicon MNs assisted SN dermal delivery led to increase of drug cutaneous retention (1.9-fold) under infinite dosing regimen, the synergistic action of solid MNs and ME applied under finite dosing was more pronounced in comparison with the application either of physical (dissolving MNs) or chemical enhancer (ME) alone. Namely, SN amount accumulated into the skin increased up to 4.67 and 4.37 folds in comparison with ME and dissolving MNs alone, respectively, while reaching a significant decrease in drug permeation through the skin compared to the use of dissolving MNs. Application of ME per se was the only approach that provided selective in vitro dermal drug delivery without SN permeation across the skin. However, despite both types of the used MNs lead to SN permeation in vitro, the ratio between the drug amount deposited in the skin and SN content permeated was significantly higher for the combined approach (12.05) than for dissolving MNs (2.10). Therefore, a combination of solid silicon MNs and biocompatible ME favoured more pronouncedly SN skin accumulation, which is preferable in the treatment of skin fungal infections.