Cystic echinococcosis (CE) is a zoonosis caused by Echinococcus spp., affecting both humans and animals’ lives. Current treatment of CE by oral administration of albendazole (ABZ) is hampered by several limitations. The poor aqueous solubility and the rapid metabolism of ABZ in the liver are the main issues, leading to lack of efficacy of the treatment. In the present study, we developed a nanocrystalline (NC) formulation of ABZ to be delivered intradermally using dissolving microneedles (DMNs). The NC formulation was developed using milling in an ultrasmall-scale device. Following several screenings, Pluronic F127 was selected as a suitable stabilizer, producing NCs with around 400 nm in size with narrow particle distribution. The crystallinity of ABZ was maintained as observed by DSC and XRD analysis. The NC approach was able to improve the dissolution percentage of ABZ by approximately three-fold. Furthermore, the incorporation of NCs into DMNs using the combination of poly­(vinylpyrrolidone) and poly­(vinyl alcohol) formed sharp needles with sufficient mechanical strength and insertion properties. Dermatokinetic studies revealed that >25% of ABZ was localized in the dermis of excised neonatal porcine skin up to 48 h after DMN administration. In in vivo pharmacokinetic studies, the AUC and relative bioavailability values of ABZ delivered by NC-loaded DMNs were found to be significantly higher than those obtained after oral administration of coarse suspension of ABZ or ABZ-NCs, as well as DMNs delivering coarse ABZ as indicated by the relative bioavailability values of >100%. Therefore, the combination approach developed in this study could maintain the systemic circulation of ABZ, which could be possibly caused by avoiding the first-pass metabolism in the liver. This could be beneficial to improve the efficacy of ABZ in CE treatment.

The poor solubility of itraconazole (ITZ) has limited its efficacy in the treatment of vaginal candidiasis. Accordingly, the improvement of ITZ solubility using a solid dispersion technique was important to enhance its antifungal activity. Besides, as the purpose of this research was to develop local-targeting formulations, bioadhesivethermosensitive in situ vaginal gel combined with the gel-flake system was found to be the most suitable choice. To obtain optimum solubility, entrapment efficiency, and drug-loading capacity, optimization of solid dispersion (SD) and gel-flake formulations of ITZ was performed using a composite central design. The results showed that the optimized formulation of SD-ITZ was able to significantly enhance its solubility in both water and simulated vaginal fluid to reach the values of 4.211 ± 0.23 and 4.291 ± 0.21 mg/mL, respectively. Additionally, the optimized formulation of SD-ITZ gel flakes possessed desirable entrapment efficiency and drug-loading capacity. The in situ vaginal gel containing SD-ITZ gel flakes was prepared using PF-127 and PF-68, as the gelling agents, with the addition of hydroxypropyl methylcellulose (HPMC) as the mucoadhesive polymer. It was found that the obtained in situ vaginal gel provided desirable physicochemical properties and was able to retain an amount of more than 4 mg of ITZ in the vaginal tissue after 8 h. Importantly, according to the in vivo antifungal activity using infection animal models, the incorporation of the solid dispersion technique and gelflake system in the formulation of the bioadhesive-thermosensitive in situ vaginal gel led to the most significant decrease of the growth of Candida albicans reaching <1 log colony-forming units (CFU)/mL or equivalent to <10% of the total colony after 14 days, indicating the improvement of ITZ antifungal activity compared to other treated groups. Therefore, these studies confirmed a great potential to enhance the efficacy of ITZ in treating vaginal candidiasis. Following these findings, several further experiments need to be performed to ensure acceptability and usability before the research reaches the clinical stage.

Extracellular tissue fluids are interesting biomatrices that have recently attracted scientists' interest. Many significant biomarkers for localized external organ diseases have been isolated from this biofluid. In the diagnostic and disease monitoring context, measuring biochemical entities from the fluids surrounding the diseased tissues may give more important clinical value than measuring them at a systemic level. Despite all these facts, pushing tissue fluid-based diagnosis and monitoring forward to clinical settings faces one major problem: its accessibility. Most extracellular tissue fluid, such as interstitial fluid (ISF), is abundant but hard to collect, and the currently available technologies are invasive and expensive. This is where novel microneedle technology can help tackle this significant obstacle. The ability of microneedle technology to minimally invasively access tissue fluid-containing biomarkers will enable ISF and other tissue fluid utilization in the clinical diagnosis and monitoring of localized diseases. This review attempts to present the current pursuit of the application of microneedle systems as a diagnostic and monitoring platform, along with the recent progress of biomarker detection in diagnosing and monitoring localized external organ diseases. Then, the potential use of various microneedles in future clinical diagnostics and monitoring of localized diseases is discussed by presenting the currently studied cases.

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To compare the effectiveness of tranexamic acid (TA) combination serum with hydroquinone, the gold standard in whitening agents for healthy populations. This was a three‐arm randomized controlled trial. The subjects were divided into three groups: the first group received 3% TA combination serum (3% TA, 4% galactomyces ferment filtrate, 2% niacinamide, and 4% alpha arbutin), the second group received 2% TA combination serum, and the third group received 4% hydroquinone. One milliliter of each serum was applied on three holes: Hole A, which was located 4 cm from the left cubital fossa, Hole B, which was located 4 cm from the first hole, and Hole C, which was located 4 cm from the right cubital fossa. The skin brightness and pigmentation intensity were evaluated each week for 4 weeks using a chromameter. A total of 44 subjects were recruited for this study. All groups showed a significant improvement in skin brightness and pigmentation intensity after 4 weeks (p < .001). There were no differences between the treatment groups and hydroquinone (p > .05). TA serum (2 and 3%) combined with 4% galactomyces ferment filtrate, niacinamide, and alpha arbutin is an effective depigmenting agent.