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[Display omitted] Psoriasis is an autoimmune disorder disease with abnormally activated T lymphocytes and thickening of the epidermis. The mechanism of the action of tacrolimus and paclitaxel are matched with the two only known pathogenesis of psoriasis. However, there has been no report on tacrolimus combined with paclitaxel in the treatment of psoriasis until now. The O/O ointment was prepared for the topical application to overcome poor solubility, poor skin penetration, and erratic absorption of the two drugs. A high-speed shearing method was adopted to prepare the ointment, in which propylene carbonate was used to solve tacrolimus and paclitaxel completely. The ointment showed excellent stability, slow release of the drugs, better retention in psoriatic skin, and good skin tolerance. The therapeutic efficacy of ointment was evaluated with imiquimod induced psoriatic model, and the level of expression of psoriatic biochemical markers was evaluated using the PASI score and immunohistochemistry. The cumulative PASI score was 10.8 for the imiquimod induced group, 7.8 for the tacrolimus ointment group, 8.3 for the paclitaxel ointment and 5.3 for the tacrolimus-paclitaxel (1:1) ointment group, respectively. Ointment group with tacrolimus and paclitaxel indicated a significant improvement in the phenotypic features of the psoriatic skin treated. Compared with the imiquimod group, tacrolimus-paclitaxel (1:1) ointment group was significantly reduced the level of IL-17. The results confirm that tacrolimus and paclitaxel co-loaded ointment can be an effective strategy for the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

Schematic diagrams of a novel topical formulation for vitamin C by using solid-in-oil. nanodispersions technology. [Display omitted] l -ascorbic acid （Vitamin C, VC） is the most abundant antioxidant in human skin. But its poor penetration into the skin and unstability limit the application. The aim of the study was to promote the topical skin permeation and retention of VC, increase the stability as well as effectiveness by a novel solid in oil nanodispersion. In the nanodispersions system, nano-sized particles of hydrophilic molecules are dispersed in an oil vehicle with the assistance of hydrophobic surfactants. The optimized formula composed of O170 and S1570 (12.5:1, w/w) showed high EE% of 98% and good stability. FTIR analysis confirmed that there may be hydrogen bond between VC and surfactants. The results of DSC, and XRD revealed that the drug was successfully encapsulated in the surfactants, which maintained the stability of drug. By analyzing and fitting the release data in vitro , the drug release mechanism of SONDs was predicted as a multi-dynamic model. Skin permeation of VC was improved 3.43-fold for SONDs compared with VC aqueous solution, highlighting that the lipophilicity and nano size of the carrier more easily penetrated into the skin. Finally, the photoaging study revealed that topical application of VC-SONDs provided the highest skin protection compared UV and VC aqueous solution treated group which was evident by the normal thick epidermal morphology, no obvious melanocytes and the densely arranged dermal elastic fibers. These results demonstrated that the solid-in-oil nanodispersions may be a potential transdermal delivery system for hydrophilic bioactive ingredients. [ABSTRACT FROM AUTHOR]

The aim of this study was to improve the oral bioavailability of a practically insoluble drug, efonidipine hydrochloride (EFH), by agglomeration in acid solution/gastric fluid. The EFH nanosuspension was prepared by the wet-milling method with F68 as a dispersing agent, SDS as an auxiliary stabilizer and l -arginine as a pH adjusting agent. The EFH nanosuspension have been prepared in industrial scale-up. The dissolution rate of the EFH nanosuspension was greater than that of bulk EFH. An in vitro intestinal permeability study showed a clear increase in the apparent permeability of different intestinal segments compared with bulk EFH. Also, a pharmacokinetic study showed that the C max and AUC 0-24h of the nanosuspensions were approximately 1.76-fold and 2.2-fold greater than that of bulk EFH, respectively, and there was no significant difference compared with commercial tablets. It appears that wet-milling offers an effective approach to improve the dissolution rate and oral absorption of this practically insoluble drug. [ABSTRACT FROM AUTHOR]