Synthetic antigenic determinants of clavulanic acid induce dendritic cell maturation and specific T cell proliferation in patients with immediate hypersensitivity reactions.

BACKGROUND: Immediate drug hypersensitivity reactions (IDHRs) to clavulanic acid (CLV) have increased in the last decades due to a higher consumption alongside amoxicillin (AX). Due to its chemical instability, diagnostic procedures to evaluate IDHRs to CLV are difficult, and current in vitro assays do not have an optimal sensitivity. The inclusion of the specific metabolites after CLV degradation, which are efficiently recognised by the immune system, could help to improve sensitivity of in vitro tests. METHODS: Recognition by dendritic cells (DCs) of CLV and the synthetic analogues of two of its hypothesised antigenic determinants (ADs) was evaluated by flow cytometry in 27 allergic patients (AP) and healthy controls (HC). Their ability to trigger the proliferation of T cells was also analysed by flow cytometry. RESULTS: The inclusion of synthetic analogues of CLV ADs, significantly increased the expression of maturation markers on DCs from AP compared to HC. A different recognition pattern could be observed with each AD, and, therefore, the inclusion of both ADs achieves an improved sensitivity. The addition of synthetic ADs analogues increased the proliferative response of CD4+ Th2 compared to the addition of native CLV. The combination of results from both ADs increased the sensitivity of proliferative assays from 19% to 65% with a specificity higher than 90%. CONCLUSIONS: Synthetic ADs from CLV are efficiently recognised by DCs with ability to activate CD4+ Th2 cells from AP. The combination of analogues from both ADs, significantly increased the sensitivity of DC maturation and T-cell proliferation compared to native CLV.

Design of a Novel Delivery Efficiency Feedback System for Biphasic Dissolving Microarray Patches Based on Poly(Lactic Acid) and Moisture-Indicating Silica.

Dissolving microarray patches (DMAPs) represent an innovative approach to minimally invasive transdermal drug delivery, demonstrating efficacy in delivering both small and large therapeutic molecules. However, concerns raised in end-user surveys have hindered their commercialization efforts. One prevalent issue highlighted in these surveys is the lack of clear indicators for successful patch insertion and removal time. To address this challenge, a color-change-based feedback system is devised, which confirms the insertion and dissolution of DMAPs, aiming to mitigate the aforementioned problems. The approach combines hydrophilic needles containing model drugs (fluorescein sodium and fluorescein isothiocyanate (FITC)-dextran) with a hydrophobic poly(lactic acid) baseplate infused with moisture-sensitive silica gel particles. The successful insertion and subsequent complete dissolution of the needle shaft are indicated by the progressive color change of crystal violet encapsulated in the silica. Notably, distinct color alterations on the baseplate, observed 30 min and 1 h after insertion for FITC-dextran and fluorescein sodium DMAPs respectively, signal the full dissolution of the needles, confirming the complete cargo delivery and enabling timely patch removal. This innovative feedback system offers a practical solution for addressing end-user concerns and may significantly contribute to the successful commercialization of DMAPs by providing a visualized drug delivery method.