Brain damage caused by cerebral ischaemia/reperfusion (I/R) can lead to handicapping. So, the present study aims to evaluate the prophylactic and therapeutic effects of geraniol in the form of intranasal polymeric mixed micelle (PMM) on the central nervous system in cerebral ischaemia/reperfusion (I/R) injury. A 3² factorial design was used to prepare and optimize geraniol PMM to investigate polymer and stabilizer different concentrations on particle size (PS) and percent entrapment efficiency (%EE). F3 possessing the highest desirability value (0.96), with a PS value of 32.46 ± 0.64 nm, EE of 97.85 ± 1.90%, and release efficiency of 59.66 ± 0.64%, was selected for further pharmacological and histopathological studies. In the prophylactic study, animals were classified into a sham-operated group, a positive control group for which I/R was done without treatment, and treated groups that received vehicle (plain micelles), geraniol oil, and geraniol micelles intranasally before and after I/R. In the therapeutic study, treated rats received geraniol oil and micelles after I/R. Evaluation of the effect of geraniol on behavior was done by activity cage and rotarod and the analgesic effect tested by hot plate. Anti-inflammatory activity was assessed by measuring interleukin β6, cyclooxygenase-2, hydrogen peroxide, and inducible nitric oxide synthase. Histopathogical examination of cerebral cortices was also done to confirm the results of a biochemical assay. Geraniol nanostructured polymeric mixed micelles showed an enhanced neuro-protective effect compared to geraniol oil, confirming that PMM via intranasal route could be an efficient approach for delivering geraniol directly to the brain through crossing the blood–brain barrier.

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

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.