D3.416 - PEG-CUR Reduces Oxidative Stress and Total Methylation Induced by Cigarette Smoke in Epithelial Cells: Development of PEG-Curcumin Loaded Fast-Dissolving Microneedle Patches

Exposure to cigarette smoke leads to an oxidant–antioxidant imbalance in the nasal epithelium. Antioxidant-based therapeutic approaches are therefore of increasing interest for mitigating cigarette smoke–induced oxidative stress. Curcumin (Cur) is a well-established antioxidant; however, its clinical applicability is limited by poor bioavailability and stability. PEGylation has been proposed as an effective strategy to improve the bioavailability of Cur. In parallel, next-generation drug delivery systems, such as microneedle-based platforms, offer translational potential for local antioxidant delivery. Accordingly, investigating the effects of Cur and PEGylated curcumin (PEG-Cur) in nasal epithelial cells, together with PEG-Cur-loaded microneedle patches, may provide valuable insights into antioxidant-based strategies against oxidative stress.

Characterization of synthesized PEG-Cur was confirmed by FT-IR, MALDI-TOF-MS, and ^¹H-NMR. RPMI 2650 nasal epithelial cells were treated with Cur/PEG-Cur (1–50 µM, 24–48 h) to determine optimal conditions, followed by exposure to cigarette smoke condensate (CSC) (0.5–200 µM, 3–48 h). Cell viability was assessed by MTT, LDH, and EtBr/Calcein-AM assays, and free radical levels by DCFH-DA. Gene expression (SEPP1, NCF2, SFTPD, CCL5, PTGS1) was analyzed by qPCR, and total methylation by ELISA. Microneedle patches were fabricated via micromolding. Double-layered arrays composed of PEG-Cur/PVA and PCL were characterized for morphology, mechanical and thermal properties, and dissolution. Skin penetration was evaluated ex vivo using murine skin and parafilm as an artificial skin model.

Preliminary experiments identified optimal conditions as 24 h with 5 µM for Cur/PEG-Cur and 24 h with 50–100 µg/mL for CSC. PEG-Cur treatment reduced cigarette smoke-induced oxidant levels by decreasing the expression of oxidant-related genes (NCF2 and CCL5) and increasing the expression of antioxidant-related genes (SEPP1 and SFTPD). Pre-treatment with Cur/PEG-Cur reduced the CSC-induced increase in total methylation. Morphological analyses confirmed the successful fabrication of conical microneedles. Ex vivo studies using mouse skin and Parafilm demonstrated effective penetration.

Pre-treatment with Cur/PEG-Cur alleviated cigarette smoke-induced oxidative stress and global DNA methylation. In addition, PEG-Cur-loaded microneedle patches demonstrated potential for enhancing transdermal drug delivery, highlighting a promising antioxidant-based supportive platform for the management of oxidative stress-related diseases.

This study was supported by TÜBİTAK (Project no: 321S161).