Barlow, H. J. | Search bioRxiv

bioRxiv2025

Determination of chemical partitioning in vehicles using a skin surrogate for dermal absorption model refinement.

In nonclinical safety assessments of cosmetic ingredients applied topically, it is essential to investigate the rate and extent of dermal penetration to reach the systemic circulation. The initial step in skin absorption involves the partitioning of an ingredient from the formulation into the upper layer of the stratum corneum and this plays a key role in determining the delivery of an ingredient. Currently, there is a lack of reliable methods to accurately predict this important parameter. To address this, we measured the partitioning of three chemicals from seven different vehicles into a surrogate PDMS membrane; these measurements were then used to parameterize a dermal absorption model. The evaluation of receptor fluid kinetics and skin absorption percentages, comparing measured and predicted data, demonstrated that incorporating the vehicle partitioning parameter derived from the PDMS system improved the accuracy of model predictions for the three chemicals in most vehicles.

pharmacology and toxicology↗

bioRxiv2024

The effect of surfactants and film-forming polymers on pulmonary surfactant function measured in vitro is dose-rate dependent

Surfactants and film-forming polymers are common ingredients in consumer spray products such as cleaning products, hair care products, and anti-perspirants. Spraying eases application by creating aerosolised droplets of the product that can distribute evenly over the treated surface. However, these aerosols can potentially be inhaled during their normal application. Droplets that reach the alveoli can interact with the pulmonary surfactant; a complex mixture of phospholipids and proteins that regulates the surface tension at the air-liquid interface. This interaction could elevate the minimum surface tension at maximum compression and change the surface rheology of the pulmonary surfactant at the interface. We tested four surfactants and seven polymers for their ability to inhibit pulmonary surfactant function in vitro and investigated if the inhibition is dose-rate dependent i.e., the product of the concentration (mg/mL) and aerosolisation rate (mL/min). We found that independent of chemical class (surfactant or polymer) there was a clear dose-rate dependent inhibition of pulmonary surfactant function and that different chemicals inhibited function at different dose-rates. We compared the points of departure of inhibitory chemicals to a polymer with known dose-rate dependent lung toxicity. When assessing the risk of chemicals that might be inhaled, it is essential to ensure normal use would not inhibit pulmonary surfactant function leading to immediate effects on the lungs. Lay summarySpray products create a cloud of tiny droplets in the air when they are used. This cloud can be inhaled, and if it reaches the deepest parts of the lungs, it can interact with the thin layer of liquid, called pulmonary surfactant, that covers the cells. It protects the lung tissue during the constant movement of breathing. Droplets can sometimes disrupt the pulmonary surfactant function, making breathing difficult. Chemicals that are used in spray products must be tested to assess if they are harmful if inhaled. In this project we studied the effect of chemicals that are commonly found in spray products on the functioning of the pulmonary surfactant in vitro. The results can be combined with other in vitro methods to test if chemicals are harmful to inhale without testing on animals.

biophysics↗

bioRxiv2024

Experiments and modelling of pulmonary surfactant disruption by aerosolised compounds

Within the deep lung, pulmonary surfactant coats the air-liquid interface at the surface of the alveoli. This complex mixture of amphiphilic molecules and proteins modifies the surface tension and mechanical properties of this interface to assist with breathing. In this study, we examine the effects on pulmonary surfactant function by two industrially used compounds composing surfactants and polymers. Using an experimental method previously developed to imitate the in vivo exposure in the alveoli[1], we quantify the change in the dilational rheology of the pulmonary surfactant due to the introduction of two widely used chemicals; Benzalkonium Chloride (BAC) and Polyhexamethylene Biguanide (PHMB). We observe that these chemicals alter the dilational rheology of the surfactant monolayer. Using a mechanistic theory, we are able to semi-quantitatively model the changes induced by the introduction of these compounds to the pulmonary surfactant.

biophysics↗