Pressure drop particle precipitation from a quasi-incompressible, ternary and liquid mixture

We found a quasi-incompressible and liquid mixture of ibuprofen, water and acetone, that enables the crystallization of ibuprofen particles by decreasing the pressure from 15MPa to ambient pressure (~0.1MPa). We measured the solubility of ibuprofen in the mixture as a function of the acetone/water-ratio for pressures of 0.1MPa, 5.5MPa and 15MPa and at 308K using the cloud point method. Based on the solubilities, binodal compositions of the ternary system were modelled using the NRTL-SAC model. The solubility of the drug in the mixture increases with increasing pressure at constant acetone/water-ratio. This pressure sensitive solubility can be exploited for the crystallization of ibuprofen particles via a pressure-drop approach. A pressure-drop from 15MPa to ambient pressure (~0.1MPa) can result in a supersaturation of up to 1.43.The project leading to this contribution has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under ERC Starting Grant agreement No. 637654 (Inhomogeneities). The ICTS “Nanbiosis”, more specifically U6 Unit, unit of the CIBER in Bioengineering, Biomaterials & Nanomedicne (CIBER-BBN), is also acknowledged for the experimental information provided. The authors acknowledge funding from the Generalitat de Catalunya through the Centres de Recerca de Catalunya (CERCA) programme and grant 2017-SGR-918, from the Ministry of Economy and Competitiveness (MINECO) of Spain through grant PID2019–105622RB-I00 (MOL4BIO).Peer reviewe

High prevalence of Merkel cell polyomavirus is associated with dysregulation in transcript levels of TLR9 and type I IFNs in a large cohort of CF patients from the Italian (Lazio) reference center for cystic fibrosis

Merkel cell polyomavirus (MCPyV) has been detected in respiratory specimens including those from Cystic Fibrosis (CF) patients, raising questions about its immunological and clinical relevance in the respiratory tract. MCPyV might promote an inappropriate antiviral response contributing to a chronic inflammatory response and resulting in detrimental effects in CF. Respiratory samples (n = 1138) were randomly collected from respiratory tract of CF patients (n = 539) during July 2018–October 2019. MCPyV-DNA detection was performed by real time PCR and positive samples were characterized by sequencing of the NCCR genomic region. The transcript levels of Toll-like receptor 9 (TLR9) and type I interferon (IFN–I) genes (IFNα, IFNβ and IFNε) were examined by real-time RT-PCR assays. MCPyV-DNA was detected in 268 out of 1138 respiratory specimens (23.5%) without any difference in the prevalence of MCPyV-DNA according to age, gender or bacteriological status of CF individuals. Thirteen out of 137 CF patients remained positive for MCPyV-DNA over the time (a median follow-up period of 8.8 months). Detection of MCPyV-DNA in respiratory specimens was not associated with the occurrence of exacerbation events. Both MCPyV positive adolescents (11–24 years) and adults (≥25 years) had lower mRNA levels of TLR9, IFNβ, IFNε and IFNα than the negative patients of the same age group, while MCPyV positive children produced increased levels of TLR9 and IFN-I genes (p < 0.05 for TLR9, IFNβ, IFNε) with respect to the negative ones. There were significant differences in TLR9 levels (p < 0.01), but not in those of IFNs, between MCPyV-DNA positive and negative patients with S. aureus, P. aeruginosa or both. Overall, these results indicate that MCPyV-DNA is frequently detected in the respiratory samples of CF patients and might influence the expression levels of IFN-related genes in an age dependent manner. The concomitant detection of MCPyV together with S. aureus and/or P. aeruginosa correlated with alterations in TLR9 levels suggesting that virus-bacteria coinfections might contribute to affect antiviral immunity in CF patients