Chitosan decorated oleosomes loaded propranolol hydrochloride hydrogel repurposed for Candida albicans-vaginal infection.

Aim: Our investigation aims to estimate the antifungal effect of propranolol hydrochloride (PNL). Methods: Oleosomes (OLs) were fabricated by thin-film hydration and evaluated for entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and amount of drug released after 6 h Q6h (%). Results: The optimal OL showed a rounded shape with optimum characteristics. The ex-vivo permeation and confocal laser scanning microscopy verified the prolonged release and well deposition of PNL-loaded OLs-gel. The in-silico assessment demonstrated the good stability of PNL with OLs' ingredients. In vivo evaluations for PNL-loaded OLs-gel showed a good antifungal impact against Candida albicans with good safety. Conclusion: This work highlights the potential of PNL-loaded OLs-gel as a potential treatment for candida vaginal infection.

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An ex vivo study of infections of vascular grafts and endografts with scanning electron microscopy.

OBJECTIVE: Vascular graft and endograft infections (VGEIs) are complicated by high morbidity, mortality, and recurrence rates, notably due to biofilm formation on the graft surface, hardly dislodgeable by the sole anti-infectious treatment. The characteristics of this biofilm are still poorly documented. The aim of this study was to evaluate ex vivo biofilm on removed infected vascular grafts and endografts (VGEs). METHODS: Explanted VGEs were prospectively collected from 2019 to 2022 at Bordeaux University Hospital, France. Two samples per graft were used for scanning electron microscopy imaging; one was sonicated, and both grafts' sides were imaged. RESULTS: A total of 26 patients were included, 18 with VGEI, eight without any infection (endoleak and/or thrombosis), and 29 VGEs were collected. Microbial documentation was obtained in 83% of VGEIs. A thick layer of fibrin was visible on almost all grafts, mixed with a dense biofilm matrix on infected grafts visible as early as 1 month after the onset of infection. Bacteria were not always visualized on infected grafts' surface (80% on outer side and 85% on luminal side) but were surprisingly present on one-third of non-infected grafts. There was no significant difference between biofilm, fibrin, and microorganisms' distribution between the two grafts' sides. However, there were clear differences between infected and non-infected grafts, since immune cells, bacteria and biofilm were more frequently visualized on both sides of infected grafts (P < .05). Bacteria and immune cells although still visible, were significantly less present after sonication; the number of other elements including biofilm was not significantly different. CONCLUSIONS: The persistence of a thick layer of fibrin and biofilm embedding microorganisms on both sides of infected VGE even after 1 month of infection could be the explanation for the low success rates of conservative management and the usual need for graft removal to treat VGEIs.

Development and optimization of kaempferol loaded ethosomes using Box-Behnken statistical design: In vitro and ex-vivo assessments.

Kaempferol (KMP) belong to flavonoid class have developed in ethosomal formulation and were evaluated for their potential to treat diabetic foot ulcers. Even though ethosomes are highly deformable, they can pass through human skin intact. KMP ethosomes were formulated using the cold method and optimized by Box-Behnken design (BBD) (three-factor, three-level (33 )). The formulation variables used for optimization are drug concentration of KMP, soylecithin content, and ethanol percentage. The optimized formulation was examined using transmission electronic microscopy (TEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, in-vitro release, ex-vivo permeation studies, and storage stability. The optimized KMP ethosomes was found to have vesicle size (VS) of 283 ± 0.3 nm and zeta potential (ZP) of -29.67 ± 0.3 mV, polydispersity index (PDI) of 0.36, % entrapment efficiency (%EE) of 91.02 ± 0.21%, drug loading (%) of 46.23 ± 2.5% followed by good storage stability at 4°C/60 ± 5% RH. In vitro drug release of optimized KMP ethosomes was 88.2 ± 2.75%, which was approximately double when compared with pure KMP release, that is 49.9 ± 1.89%. The release kinetics for optimized KMP ethosomes follows the Korsmeyer-Peppas model. An apparent permeation coefficient of 356.25 ± 0.5 µg/cm2 was determined and compared with pure KMP (118.46 ± 0.3 µg/cm2 ) for 24 h. According to the study, ethosomes can be a cutting-edge strategy that offers a new delivery method for prolonged and targeted distribution of KMP in a variety of dosage forms including oral, topical, transdermal, and so forth.

A Comparative Pharmacokinetic Study for Cysteamine-Containing Eye Drops as an Orphan Topical Therapy in Cystinosis.

Cystinosis is a low-prevalence lysosomal storage disease. The pathomechanism involves abnormal functioning of the cystinosine lysosomal cystine transporter (CTNS), causing intraliposomal accumulation of the amino acid cysteine disulfide, which crystallizes and deposits in several parts of the body. The most common ophthalmic complication of cystinosis is the deposition of "gold dust" cystine crystals on the cornea, which already occurs in infancy and leads to severe photosensitivity and dry eyes as it gradually progresses with age. In the specific treatment of cystinosis, preparations containing cysteamine (CYA) are used. The availability of commercialized eyedrops for the targeted treatment is scarce, and only Cystadrops® are commercially available with strong limitations. Thus, magistral CYA-containing compounded eyedrops (CYA-CED) could have a key role in patient care; however, a rationally designed comprehensive study on the commercialized and magistral products is still missing. This work aims to build up a comprehensive study about commercialized and magistral CYA eye drops, involving pharmacokinetic and physicochemical characterization (applying mucoadhesivity, rheology test, investigation of drug release, and parallel artificial membrane permeability assays), as well as ex vivo tests, well supported by statistical analysis.

Age-related changes on physicochemical properties of the artificial vitreous humor: A practical tool for enhancing ex vivo studies.

The vitreous humor (VH) is a hydrophilic, jelly-like ocular fluid, which is located in the posterior chamber of the eye. The rheological, structural, and chemical properties of VH change significantly during aging, which further causes eye-associated diseases and could be a potential indicator for various diseases. In this study, artificial VH (A-VH) samples were created by taking into account different age groups to observe age-related changes in the physicochemical properties of these samples. This study aimed to measure the physicochemical properties of age-dependently prepared A-VH samples to determine the changes with aging in the physicochemical properties of A-VH samples. Phosphate-buffered saline (PBS)-based A-VH samples were prepared in three types representing adult, middle-aged, and elder individuals. Age-related changes in physicochemical properties (surface tension, osmolality, pH, relative viscosity, density, and refractive index) were analyzed by related equipment. The A-VH samples, prepared using PBS, showed strong similarity to authentic VH in terms of physicochemical properties. While the age-related changes studies have revealed some discrepancies between age-dependently prepared A-VH samples in terms of surface tension, osmolality, relative viscosity, and pH with high correlation coefficients (r2 > 0,94), density and refractive index values did not show any significant differences and correlation between types of A-VH representing 3 age groups. In conclusion, age-dependent A-VH samples were created successfully to use ex vivo method development studies, and the influence of aging on the physicochemical properties of VH was demonstrated as well.