Dr Mohammed Mahmoud Youssif

This research focused on developing Terconazole (TCZ)-loaded flexogel to improve local therapy of vaginal fungal infections. A 23 full factorial design was employed to investigate the influence of phosphatidylcholine content, terpene-to-drug ratio, and Tween 80 concentration on the physicochemical characteristics of Flexosomes. The vesicles were prepared via the ethanol injection technique and optimized using Design-Expert® software. Key parameters analyzed included entrapment efficiency (EE%), vesicle size (VS), polydispersity index (PDI), and zeta potential (ZP). Optimization criteria involved maximizing EE% and the absolute value of ZP, while minimizing VS and PDI. The optimized formulation exhibited a high desirability score of 0.909, with EE% of 89.53 %, VS of 93.63 nm, and ZP of −29.05 mV. Comprehensive characterization revealed pseudo-plastic rheological behavior, a biphasic in vitro release profile, and structural integrity supported by FTIR and TEM analyses. The formulation also maintained stability over 3 months with no significant changes in key attributes. Ex vivo permeation studies through rabbit vaginal tissue revealed superior drug penetration and accumulation compared to TCZ suspension. In vivo confocal microscopy further confirmed enhanced mucosal penetration depth (145 μm vs. 55 μm), while histopathological evaluation demonstrated excellent mucosal safety with no signs of irritation or inflammation. Collectively, these results highlight the potential of TCZ-loaded flexosomes as a promising nanocarrier for the safe and effective treatment of vaginal candidiasis.

Polymeric microneedle array patches (MAPs) offer a painless and convenient way for delivering drugs across various biological membranes, including the skin, the cornea and various mucosal surfaces. Conventionally, dissolving MAPs provide rapid drug release but have a limited drug-loading capacity. Hydrogel-forming MAPs can prolong drug release typically for no more than several weeks but often involve harsh manufacturing conditions, such as elevated temperatures above 60 °C for chemical crosslinking. For both types of MAPs, the drug release kinetics depends greatly on the physical properties of the polymers used. However, common polymers used for MAP formulation are very constrained in their ability to balance often conflicting requirements in terms of water solubility, swellability, mechanical strength and manufacturability. To overcome these constraints, this study presents a semi-dissolving, hydrogel-forming MAP formulation approach based on a dual-domain polymeric system, consisting of physically and functionally distinct water-soluble polyvinylpyrrolidone and insoluble chitosan-hydrogel domains. In this unique formulation approach, robust MAPs were produced via micromoulding, using only a hydroalcoholic solvent system and mild temperatures ≤ 37 °C. The drug payload was incorporated into the entire baseplate of the MAPs using one-pot synthesis, which offers not just a high drug-loading capacity but also ease of manufacture. The MAPs extended the in vitro release of dexamethasone sodium phosphate (DSP), a highly hydrophilic drug, to over two months. Kinetic modelling showed that drug release from the MAPs followed non-Fickian transport. The DSP released from the MAPs retained potent anti-inflammatory activity in ex vivo human peripheral blood mononuclear cells. Using microscopy, timelapse imaging and kinetic data, the mechanism of drug release was captured in terms of the structural transformation of the polymeric matrix following hydration. It is proposed that this formulation approach may be extended to other dosage forms, such as implants, to modulate the release of a multitude of drugs, including biologics.

: This study aims to develop an intranasal (IN) delivery system for glioblastoma multiforme (GBM) management using repurposed superparamagnetic iron-oxide (SPION) loaded with atorvastatin (ATO)-nanostructured lipid carrier (NLC). : Emulsification and ultrasonication were used to formulate ATO-NLCs, and the best formula was loaded with SPION to make the final atorvastatin/superparamagnetic iron oxide-loaded nanostructured lipid carrier (ASN) formulation. Entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and drug release after 6 h (Q6h) were evaluated for NLCs. ASN was tested for cytotoxicity on T98G cancer cells, and the cell cycle was examined to determine cell death. Furthermore, the ability of the optimal formulation to suppress the levels of inflammatory biomarkers was investigated in Lipopolysaccharide (LPS)-induced inflammation. The brain-targeting behavior of IN-ASN was visualized in rabbits via confocal laser scanning microscopy (CLSM). : The optimum NLC exhibited a spherical shape, EE% of 84.0 ± 0.67%, PS of 282.50 ± 0.51 nm, ZP of -18.40 ± 0.15 mV, and Q6h of 89.23%. The cytotoxicity of ASN against cancer cells was 4.4-fold higher than ATO suspension, with a 1.3-fold increment in cell apoptosis. ASN showed significantly reduced pro-inflammatory biomarkers (IL-β, IL-6, TNF-α, TLR4, NF-қB), whereas CLSM revealed enhanced brain delivery with no observed histopathological nasal irritation. The in silico analysis demonstrated enhanced ATO-ADME (absorption, distribution, metabolism, and excretion) properties, while the network pharmacology study identified 10 target GBM genes, among which MAPK3 was the most prominent with a good binding score as elucidated by the simulated docking study. : These findings may present ATO/SPION-NLCs as significant evidence for repurposing atorvastatin in the treatment of glioblastoma multiforme.

INTRODUCTION: Natural skincare products and cosmetic preparations have gained popularity among consumers in recent years, prompting cosmetic companies to develop more natural offerings. These products often incorporate plant extracts known for their anti-aging, anti-wrinkle, and depigmentation properties.

METHODS: Using gas chromatography-mass spectrometry, this study examined the volatile compounds in both fresh and dry (key lime) fruit essential oils. The oils' anti-aging and antioxidant activities were assessed through anti-collagenase and anti-elastase assays.

RESULTS: analysis revealed good inhibition of elastase and collagenase enzymes by fresh key lime essential oil, with IC values of 145.02 and 63.97 μg/mL, respectively, compared to positive controls (daidzein for collagenase, piroxicam for elastase), in comparison to dry key lime oil (IC = 223.14 and 109.57 μg/mL, respectively). The antioxidant activity of the oils was evaluated using the ABTS (2,2'-azino-bis(3-ethylbenzothiazoline6-sulfonic acid)) radical scavenging assay. The fresh key lime oil demonstrated stronger antioxidant activity (37.76 ± 0.80 μM Trolox equivalent (TE)/g) compared to the dry key lime oil (27.76 ± 1.11 μM TE/g), suggesting that it retains more bioactive compounds essential for radical scavenging activity. Additionally, molecular docking was performed to analyze interactions between the main metabolites and the targeted enzymes active sites. Molecular docking analysis showed excellent binding scores for the three main metabolites.

CONCLUSION: The anti-aging potential of fresh key lime essential oil may be attributed to its major compounds. These findings suggest that key lime essential oil could be a promising natural ingredient for anti-aging skincare formulations.