Voriconazole, a potent antifungal agent, has emerged as a promising candidate for managing vulvovaginal candidiasis. The market availability of voriconazole as tablets or injections, along with potential side effects, highlights the need for a successful alternative delivery system. Through comprehensive experimental design, voriconazole-loaded spanlastics were developed using a 3²-factorial design. The optimized system based on factorial outcomes exhibited desirable characteristics in terms of entrapment efficiency (74.31 ± 0.39%), vesicle size (246.4 ± 2.2 nm), polydispersibility index (0.369 ± 0.01), & zeta potential (-37.5 ± 0.17 mV). Further characterization for the optimized system was performed in terms of transmission electron microscopy, Fourier transform infrared spectroscopy, and in-vitro antifungal assessment, where the latter showcased the potent effectiveness of voriconazole against various Candida species. Moreover, the integration of the optimized voriconazole-loaded spanlastic system into a gel was implemented for the assessment of ex-vivo permeation through the vaginal mucosa of rats, where the optimized system gel revealed a remarkable 1.3-fold enhancement in permeation relevant to the control VCZ gel. Notably, the clinical performance of optimized system gel was involved in a randomized controlled study for assessment of safety and efficacy in comparison to a market product (Canesten^® 2% clotrimazole). Clinical evaluation revealed that the optimized VCZ-loaded SP gel and the market product, Canesten. (2% clotrimazole) exhibited comparable efficacy in terms of clinical satisfaction, side effects, and time to clinical cure from VVC. These findings highlight the potential of the optimized system as a promising approach for improved treatment outcomes in women with vaginal candidiasis with no adverse effects. Graphical Abstract

The present study aimed to develop fast melting tablets (FMTs) using silymarin (SM) owing to FMTs rapid disintegration and dissolution. FMTs represent a pathway to help patients to increase their compliance level of treatment via facile administration without water or chewing beside reduction cost. One of the methods for FMTs formulation is lyophilization. Optimization of SM-FMTs was developed via a 3² factorial design. All prepared SM-FMTs were evaluated for weight variation, thickness, breaking force, friability, content uniformity, disintegration time (DT), and % SM released. The optimized FMT formula was selected based on the criteria of scoring the fastest DT and highest % SM released after 10 min (Q₁₀). Optimized FMT was subjected to Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) besides investigating its lung-protective efficacy. All SM-FMT tablets showed acceptable properties within the pharmacopeial standards. Optimized FMT (F7) scored a DT of 12.5 ± 0.64 Sec and % SM released at Q₁₀ of 82.69 ± 2.88%. No incompatibilities were found between SM and excipients, it showed a porous structure under SEM. The optimized formula decreased cytokines, up-regulated miRNA133a, and down-regulated miRNA-155 and COX-2 involved in the protection against lung toxicity prompted by HgCl₂ in a manner comparable to free SM at the same dosage.

Purpose: The repositioning of previously approved drugs is occupying the researchers’ plans. Baclofen (Bac) was our candidate for its established neuroprotective capacity, with a proposal of efficient drug delivery as non-ionic surfactant-based nanovesicles (NISNV) formulae against mild repetitive traumatic brain injury (mRTBI) in rats, thus reducing the number of orally or injected medications, especially in severely comatose patients or pediatrics. Methods: A (23 ) factorial design was implemented for confining Bac-loaded NISNV formulae, where a bunch of variables were inspected. An in-vivo experiment was done to test the prepared formula’s efficacy transdermally. The following parameters were measured: brain expression of gamma amino butyric acid B (GABAB), protein kinase C- α (PKC-α), focal adhesion kinase (FAK), TNF-α and nuclear factor kappa B (NF-κB) p65, malondialdehyde (MDA), superoxide dismutase (SOD), and histopathology. Results: The particle size (PS) and entrapment efficiency percent (EE%) speckled from 60.40±0.28% to 88.02±0.01% for the former and 174.64±0.93 to 1174.50±3.54 nm for the latter. In vitro release% after 8 hours ranged from 63.25±5.47% to 84.79±3.75%. The optimized formula (F4) illustrated desirability=1, with 630.09±3.53 µg/cm2 of Bac permeated over 8 hours, which equates to 100% of Bac. Bac post-trauma treatment restored brain expression of GABAB and PKC-α, while decreasing FAK. Besides enhancing the histological findings, the anti-inflammatory effect was clear by decreasing TNF-α and NF-κB p65. Consequently, significant antioxidant sequelae were revealed herein by diminishing MDA levels and restoring SOD activity. Conclusion: Transdermal delivery of Bac-loaded niosomes confirmed neuroprotection and succeeded in surpassing skin-to-brain barriers, which makes it a promising therapeutic option for repeated traumas.

Purpose: Fungal infections remain a major concern due to rising incidence related to immunosuppression and chemotherapy, alongside growing antifungal resistance. Though Voriconazole (VCZ) displays robust potential against infections like aspergillosis and candidemia , its limited formulation availability highlights the need for alternative delivery approaches. Nanovesicle-based systems like novasomes (NV) have emerged as promising systems capable of enhancing delivery and overcoming current therapeutic limitations. Methods: 2 ³ factorial design was adopted to develop VCZ-loaded NV, with optimization based on entrapment efficiency (EE), vesicle size (VS), polydispersity index (PDI), and zeta potential (ZP), alongside evaluation of in-vitro release behavior, antifungal activity, Fourier transform infrared spectroscopy (FTIR), morphological characteristics, and stability of the optimized formula. The optimized formulation was incorporated into a Carbopol gel (DN1G) for ex vivo permeation studies. Results: The formulation was optimized through a 2³ factorial design with EE%, VS, PDI, and ZP as critical responses, yielding the optimized VCZ-loaded NVs (DN1) with EE% (97.27±0.12 %), VS (256.93±4.40 nm), PDI (0.27±0.00), and ZP (-47.63±0.92 mV). In-vitro release studies confirmed controlled and sustained release. FTIR showed compatibility with the excipient, TEM analysis revealed spherical, non-aggregated vesicles, and stability evaluation revealed no significant alterations in selected parameters. DN1 demonstrated potent antifungal activity (MIC of 0.25 µg/mL) against C. albicans, and its incorporation into gel (DN1G) enhanced VCZ permeation by 1.89-fold. Conclusion: This study highlights the potential of NV as a promising approach for VCZ, offering an effective alternative to conventional VCZ formulations, and encourages further exploration of vesicular systems for antifungal therapy. Graphical