The Potential of Corchorus olitorius Seeds Buccal Films for Treatment of Recurrent Minor Aphthous Ulcerations in Human Volunteers.

Aphthous ulcers are very common disorders among different age groups and are very noxious and painful. The incidence of aphthous ulcer recurrence is very high and it may even last for a maximum of 6 days and usually, patients cannot stand its pain. This study aims to prepare a buccoadhesive fast dissolving film containing Corchorus olitorius seed extract to treat recurrent minor aphthous ulceration (RMAU) in addition to clinical experiments on human volunteers. An excision wound model was used to assess the in vivo wound healing potential of Corchorus olitorius L. seed extract, with a focus on wound healing molecular targets such as TGF-, TNF-, and IL-1. In addition, metabolomic profiling using HR-LCMS for the crude extract of Corchorus olitorius seeds was explored. Moreover, molecular docking experiments were performed to elucidate the binding confirmation of the isolated compounds with three molecular targets (TNF-α, IL-1ß, and GSK3). Additionally, the in vitro antioxidant potential of C. olitorius seed extract using both H2O2 and superoxide radical scavenging activity was examined. Clinical experiments on human volunteers revealed the efficiency of the prepared C. olitorius seeds buccal fast dissolving film (CoBFDF) in relieving pain and wound healing of RMAU. Moreover, the wound healing results revealed that C. olitorius seed extract enhanced wound closure rates (p ≤ 0.001), elevated TGF-ß levels and significantly downregulated TNF-α and IL-1ß in comparison to the Mebo-treated group. The phenotypical results were supported by biochemical and histopathological findings, while metabolomic profiling using HR-LCMS for the crude extract of Corchorus olitorius seeds yielded a total of 21 compounds belonging to diverse chemical classes. Finally, this study highlights the potential of C. olitorius seed extract in wound repair uncovering the most probable mechanisms of action using in silico analysis.

Anti-otomycotic potential of nanoparticles of Moringa oleifera leaf extract: an integrated in vitro, in silico and phase 0 clinical study.

Otomycosis is a serious superficial mycotic infection of the outer ear canal caused by some pathogenic species of Candida and Aspergillus. The infection remains a challenge to clinicians owing to the incomplete efficacy of market-available antifungal agents and high recurrence rates. The Moringa oleifera leaf ethanol extract showed efficacy against Candida albicans SC5314, compared to Nystatin® as a reference with MIC values of 7 and 718.33 µg ml-1, respectively. The extract was mixed with lecithin and chitosan to give Moringa core/shell giant nanoparticles, with a good zeta potential (+59.2 mV), a suitable entrapment efficiency (61%) and an enhanced release reaching up to 90% at 8 h. Clinical isolates from oomycote patients were identified via DNA sequencing as Candida parapsilosis, Aspergillus niger and Aspergillus flavus, and the effect of the prepared nanoparticles was tested against them via disk diffusion assay to give inhibition zones of 75, 55 and 55 mm, compared to Nystatin® with 35, 25 and 20 mm, respectively. Interestingly, patients treated with the Moringa-loaded nanoparticles experienced improvement within 1 week with no recurrence for more than 3 months. To have some insight into the bioactive components in the Moringa extract, LC-HRMS-based identification has been employed which led to the annotation of 27 compounds. Subsequent comprehensive in silico investigation suggested some alkaloids to be responsible for the activity targeting the fungal 14-α-demethylase enzyme (CYP51B). Our study revealed that Moringa extract-loaded nanoparticles attained an enhanced antifungal efficacy compared to Nystatin® and therefore they can be employed against invasive and drug-resistant otomycotic infections.

A novel nasal co-loaded loratadine and sulpiride nanoemulsion with improved downregulation of TNF-α, TGF-ß and IL-1 in rabbit models of ovalbumin-induced allergic rhinitis.

PURPOSE: The work aimed to develop a co-loaded loratadine and sulpiride nasal nanoemulsion for allergic rhinitis management. METHODS: Compatibility studies were conducted adopting differential scanning calorimetry and Fourier transform infrared spectroscopy. Nanoemulsion formulations were prepared using soybean lecithin, olive oil and tween 80. Sodium cholate and glycerol were employed as co-surfactants. Nanoemulsions were assessed for viscosity, pH, droplet size, polydispersity index, zeta potential, electrical conductivity, entrapment, In vitro drug release and corresponding kinetics. Stability of the selected formulation was investigated. The biological effectiveness was evaluated in rabbit models of ovalbumin-induced allergic rhinitis by measuring TNF-α, TGF-ß and IL-1. RESULTS: Compatibility studies revealed absence of drug/drug interactions. Nanoemulsions exhibited > 90% entrapment efficiency. The selected nanoemulsion demonstrated small droplet size (85.2 ± 0.2 nm), low PDI (0.35 ± 0.0) and appropriate Zeta Potential (-23.3 ± 0.2) and stability. It also displayed enhanced in vitro drug release following the Higuashi Diffusion and Baker-Lonsdale models. The mean relative mRNA expression of TNF-α, IL-1 and TGF-ß significantly decreased from 9.59 ± 1.06, 4.15 ± 0.02 and 4.15 ± 0.02 to 1.28 ± 0.02, 1.93 ± 0.06 and 1.56 ± 0.02 respectively after treatment with the selected nanoemulsion formulation. CONCLUSION: The results reflected a promising potent effect of the combined loratadine and sulpiride nasal nanoemulsion in managing the symptoms of allergic rhinitis.