The researchers Santiago Grijalvo (Colloidal and Interfacial Chemistry) and Xavier Rovira (Medicinal Chmistry and Synthesis) will participate in this seminar session of Scientific Vermouth, on 16th April at 12:00h, with the following talks:
- Santiago Grijalvo – PEGylated PLGA Nanoparticles Prepared from Nano-Emulsion Templates as Platforms to Cross Blood-Brain Barrier Models
The effective delivery of therapeutic molecules to the brain remains a major challenge due to the restrictive nature of the blood–brain barrier (BBB). Polymeric nanocarriers, particularly those based on PLGA, offer promising opportunities for enhancing drug transport across this interface. In this work, we developed PEGylated PLGA nanoparticles encapsulating the antioxidant rosmarinic acid (RA) and evaluated their physicochemical properties, stability, and performance in BBB models. Nanoparticles were prepared using nano emulsion templating followed by covalent PEGylation with PEG chains of different molecular weights. The resulting formulations exhibited high encapsulation efficiency and sizes below 100 nm, favourable for BBB permeation. PEG750 provided superior conjugation efficiency compared to PEG5000, yielding nanoparticles with enhanced colloidal stability and sustained RA release. Antioxidant activity was preserved following encapsulation, although with reduced potency due to controlled diffusion. Cellular assays demonstrated high biocompatibility across neuronal, astrocytic, endothelial, and pericytic cell lines, along with efficient internalization analysed by fluorescence microscopy and flow cytometry. Permeability studies using a BBB on chip microfluidic platform showed that PEGylation moderately reduced permeability compared with non modified nanoparticles, reflecting a balance between stealth properties and transport efficiency. These results highlight the potential of PEGylated PLGA nanoparticles as adaptable platforms for BBB targeted delivery. Future work will explore alternative PEG architectures and surface densities to further optimize transport across endothelial brain interfaces. - Xavier Rovira – Optimal Light‑Activated Photoswitches Targeting the Vitamin D Receptor for Therapeutic Applications in Psoriasis
Psoriasis is a chronic inflammatory skin disorder for which existing systemic therapies frequently present safety limitations, particularly due to off‑target effects. Activation of the vitamin D receptor (VDR) has demonstrated substantial therapeutic potential. However, the clinical development of VDR agonists has historically been restricted by the risk of hypercalcemia resulting from systemic modulation of calcium homeostasis. In this presentation, we report the development of optimal light‑activated photoswitchable VDR agonists designed to enable precise, localized, and reversible control of receptor activity. These ligands are azobenzene‑based photoswitches that maintains the molecules in a completely inactive state in the dark allowing to selectively activate the drug action upon exposure to clinically compatible visible blue light or UVB wavelengths.
The optimized lead compound, PhotoVDRM, was characterized through hydrogen/deuterium exchange mass spectrometry to define its receptor‑binding dynamics and conformational impact on VDR. Importantly, functional evaluation in a murine model of psoriasis‑like inflammation demonstrated that localized illumination of PhotoVDRM‑treated skin produced a strong anti‑inflammatory effect without altering systemic calcium levels.
Overall, these results provide the first evidence that photocontrolled VDR activation can dissociate therapeutic efficacy from calcemic toxicity, addressing a longstanding barrier in VDR‑targeted drug development. This approach establishes a robust platform for a new generation of dermatological therapies based on spatiotemporally precise photopharmacology targeting VDR, offering improved safety, reversibility, and mechanistic control compared with conventional small‑molecule agonists.
