Solid inclusion complex between hydroxypropyl-β-cyclodextrin (HP-β-CD) and minoxidil (MXD) was prepared by freeze-drying and characterized by yield, drug loading and dissolution rate. Moreover, the complex was formulated as alginate gel (GEL HP-β-CD)/MXD 3.5% w/w). The efficacy of the novel GEL HP-β-CD)/MXD 3.5% w/w and of MXD 3.5% w/w ethanolic/propylene-glycol solution (MXD solution) were evaluated by monitoring the hair growth of dorsal skin 1-4 weeks after depilation followed by histological analysis and gene expression in skin biopsies in male rat. Patch-clamp experiments and cell-dehydrogenase activity (CDA) were performed to evaluate the capability of the formulations to activate "in vitro" the ATP-sensitive K+-channels (KATP) and their effects on cell viability in skin fibroblasts. After 3 weeks, the MXD solution and MXD/HP-β-CD GEL enhanced the hair growth, respectively, of 80.1 ± 2% and 84.3 ± 4% vs controls. After 4 weeks, the MXD/HP-β-CD GEL significantly enhanced the hair length and bulb diameter vs others groups. The MXD/HP-β-CD GEL significantly enhanced the mRNA levels of the SUR2 and Kir6.1 subunits of the KATP channels and AKT2 vs other groups. The AR gene was down-regulated vs controls following the treatment with either MXD formulations. Either MXD (10-4 M) formulations were effective in potentiating the KATP currents. The MXD solution and its vehicle after 9 h of incubation time, but not MXD/HP-β-CD, reduced CDA in fibroblasts. In sum, the MXD/HP-β-CD GEL shows a favorable profile following topical long-term use.
Keywords: Alopecia; Barium ions (PubChem CID: 24414); Ethanol (PubChem CID: 702); GEL formulation; Gene expression; Glybenclamide (PubChem CID: 3488); Hair growth; Hydroxylpropyl-β-cyclodextrin; Hydroxypropil beta cyclodextrin (PubChem CID: 44134771); Inclusion complex; KATP channels; Minoxidil; Minoxidil (PubChem CID: 4201); Propylene glycol (PubChem CID: 174); Tetraethylammonium (TEA) (PubChem CID: 5413).
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