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- Application of curcuminoids in inflammatory, neurodegenerative and aging conditions - Pharmacological potential and bioengineering approaches to improve efficiencyPublication . Lagoa, Ricardo; Rajan, Logesh; Violante, Cristiana; Babiaka, Smith B.; Marques da Silva, Dorinda; Kapoor, Bhupinder; Reis, Flávio; Atanasov, Atanas G.Curcumin, a natural compound found in turmeric, has shown promise in treating brain-related diseases and conditions associated with aging. Curcumin has shown multiple anti-inflammatory and brain-protective effects, but its clinical use is limited by challenges like poor absorption, specificity and delivery to the right tissues. A range of contemporary approaches at the intersection with bioengineering and systems biology are being explored to address these challenges. Data from preclinical and human studies highlight various neuroprotective actions of curcumin, including the inhibition of neuroinflammation, modulation of critical cellular signaling pathways, promotion of neurogenesis, and regulation of dopamine levels. However, curcumin’s multifaceted effects - such as its impact on microRNAs and senescence markers - suggest novel therapeutic targets in neurodegeneration. Tetrahydrocurcumin, a primary metabolite of curcumin, also shows potential due to its presence in circulation and its anti-inflammatory properties, although further research is needed to elucidate its neuroprotective mechanisms. Recent advancements in delivery systems, particularly brain-targeting nanocarriers like polymersomes, micelles, and liposomes, have shown promise in enhancing curcumin’s bioavailability and therapeutic efficacy in animal models. Furthermore, the exploration of drug-laden scaffolds and dermal delivery may extend the pharmacological applications of curcumin. Studies reviewed here indicate that engineered dermal formulations and devices could serve as viable alternatives for neuroprotective treatments and to manage skin or musculoskeletal inflammation. This work highlights the need for carefully designed, long-term studies to better understand how curcumin and its bioactive metabolites work, their safety, and their effectiveness.
- Permeation studies of chlorpyrifos through skin and synthetic membranes to improve the in vitro dermal absorption assay of lipophilic compounds with ethanolic receptorsPublication . Marques da Silva, Dorinda; Franco, Margarida; Lagoa, Ricardo; Violante, CristianaThe in vitro percutaneous absorption assay is standardized, but the common use of 50 % ethanol in the receptor compartment for lipophilic compounds is questioned. In parallel, the demand for animal-free methodologies is driving the application of synthetic membranes without standardization guidelines. To address these issues, this study investigated the permeation of the lipophilic compound chlorpyrifos using different ethanol-containing receptor fluids with human and pig skin ex vivo, and silicone and STRAT-M® membranes. The results considered several factors, particularly chlorpyrifos solubility and the contact angles between skin models and receptor fluids. Original experimental approaches demonstrated that ethanol from the receptor rapidly crosses to the donor compartment increasing chlorpyrifos diffusivity. Compared to the described in vivo dermal absorption, human skin and STRAT-M® yielded the best predictive permeation parameters. However, high percentage of ethanol in the receptor fluid can lead to an overestimation of percutaneous absorption. Summing up, it is important to carefully determine the concentration of ethanol to be used in the receptor fluid of lipophilic compounds’ assays while further research with synthetic membranes is needed prior to their wider adoption.