Biology subjects

Dailey, L. A.

Publications and source records attributed to Dailey, L. A..

3 recordsLinked to original sources

bioRxiv2026

Investigation of sterile hydrogels as topical vehicles for APOSEC™, a stressed peripheral blood mononuclear cell secretome for the treatment of poorly healing wounds

APOSECTM, a complex mixture of secreted proteins, lipids, and extracellular vesicles from stressed peripheral blood monocytes, is currently in clinical trials for the treatment of chronic, poorly healing wounds. When applied to open wounds, 1 mL reconstituted APOSECTM lyophilisate is syringe-mixed with 3 g sterile hydrogel prior to administration. This study investigates the pharmaceutical performance of this novel administration system. A gel formulation (APOgel) was developed for terminal sterilisation in pre-filled syringes with post-sterilisation viscosity ([~]325-350{square}Pa*s at 1{square}s-1) comparable to a commercial benchmark gel. Syringe mixing of APOgel with a liquid APOSECTM surrogate (3:1) reduced viscosity by [~]67% but was highly reproducible across different operators (CV < 6%). Administration of three sequential dose units of the mixture from the syringe revealed an [~]20% higher content of active ingredients in the first and final dispensed compared to the middle unit, indicating non-uniform mixing in the closed syringe system. In vitro release studies over 72{square}h showed a 32% and 48% higher release of a small molecule marker and total proteins from the sterile APOgel compared to the benchmark gel as well as more pronounced gel swelling. However, efficacy studies in a murine wound healing model showed no significant difference between APOgel and the benchmark. These findings indicate that terminal sterilisation of gels for topical applications may provide benefits for more rapid release of active agents but syringe mixing of gels and a liquid requires optimisation to ensure uniform drug distribution. HighlightsO_LIAn autoclavable hydrogel for APOSECTM delivery was developed C_LIO_LIA novel syringe-mixing system for combining a gel with a liquid with subsequent dispensing of different volume units showed non-homogenous active ingredient distribution C_LIO_LIFinal optimised APOSECTM-APOgel formulation maintains functional wound-healing efficacy C_LI

pharmacology and toxicology↗

bioRxiv2026

The attachment rate of Vibrio anguillarum strains to microplastics strongly varies with abiotic and biotic factors

Microplastics (MPs), resulting from plastic objects and waste degradation, are increasingly abundant, particularly in marine environments. They exhibit a hydrophobic surface on which biofilms form easily. Metagenomic analyses of these biofilms have revealed that they often contain bacterial species potentially pathogenic to humans or animals. For this reason, MPs are suspected to present a risk for public health by acting as a vector for pathogenic bacteria species. To better understand this hazard, we studied different factors potentially affecting the bacterial attachment rate to MPs. Focusing on the fish pathogen Vibrio anguillarum, a collection of 16 strains was assembled and GFP-labelled. Their attachment rates were measured using fluorescence microscopy on three types of MPs (milled polypropylene and polyethylene terephthalate particles and commercially available polystyrene beads). A strong effect of the particle type was found, likely linked to both the chemical composition of the particles and the surface characteristics, with higher attachment rates on rough particles. Our results also revealed a strong intra-specific variation in attachment rate, highlighting the need of testing several strains of the same species to assess attachment rate and related hazards. Finally, it was observed that when a biofilm already formed on the MPs (by field-incubation of the MPs along the Mediterranean French coast), differences in attachment rates between particle types were erased. It was concluded that the attachment rate of V. anguillarum depends on a combination of biotic and abiotic factors, which makes risk assessment of MPs as vectors of pathogenic bacteria species a very complex task.

microbiology↗

bioRxiv2021

Lactate production can function to increase human epithelial cell iron concentration

Iron is an essential micronutrient required by every cell, inclusive of both prokaryotes and eukaryotes. Under conditions of limited iron availability, plants and microbes evolved mechanisms to acquire iron which include carbon metabolism reprogramming, with the activity of several enzymes involved in the Krebs cycle and the glycolytic pathway being stimulated by metal deficiency. Following release, resultant carboxylates/hydroxycarboxylates can function as ligands to complex iron and facilitate its solubilization and uptake, reversing the deficiency. Human epithelial tissue may produce lactate, a hydroxycarboxylate, during absolute and functional iron deficiency in an attempt to import metal to reverse limited availability. Here we investigate 1) if lactate can increase cell metal import, 2) if lactic dehydrogenase (LDH) activity in and lactate production by cells correspond to metal availability, and 3) if blood concentrations of LDH in a human cohort correlate with indices of iron homeostasis. Exposures of Caco-2 cells to both Na lactate and ferric ammonium citrate (FAC) increased metal import relative to FAC alone. Fumaric, isocitric, malic, and succinic acid exposure revealed that FAC co-incubation similarly increased iron import relative to FAC alone. Increased iron import following exposures to Na lactate and FAC elevated both ferritin and metal associated with mitochondria. LDH in Caco-2 cell scrapings did not change after exposure to deferoxamine but decreased with 24 hr exposure to FAC. Lactate levels in both the supernatants and cell scrapings revealed decreased levels at 4, 8, and 24 hr with FAC. In the National Health and Nutrition Examination Survey (NHANES 2005-2010), Spearman correlations demonstrated significant negative relationships between LDH concentrations and serum iron. We conclude that iron import in human cells can involve lactate, LDH activity can reflect the availability of this metal, and blood LDH concentrations can correlate with indices of iron homeostasis.

bioengineering↗