PEGylated curcumin for cigarette smoke-induced oxidative stress: From nasal epithelial cells to fast- dissolving microneedle patches
International Journal of Pharmaceutics, cilt.703, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 703
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.ijpharm.2026.127370
- Dergi Adı: International Journal of Pharmaceutics
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO)
- Anahtar Kelimeler: Antioxidants, Cigarette smoke, Epigenetic, Microneedles, PEG-Curcumin
- Hacettepe Üniversitesi Adresli: Evet
Özet
Oxidative stress induced by inhaled oxidants, particularly cigarette smoke, contributes to the development of several acute and chronic respiratory diseases through oxidative damage and epigenetic alterations. Curcumin (CUR), a well-characterized natural polyphenol with potent antioxidant and anti-inflammatory properties, is considered a promising agent for modulating oxidative stress-related signaling pathways and epigenetic mechanisms; however, its poor aqueous solubility and bioavailability limit its clinical application. Therefore, in the present study, PEGylated curcumin (PEG-CUR) was investigated as a modified CUR formulation for subsequent incorporation into a dissolving microneedle-based intranasal delivery system. Exposure to cigarette smoke condensate (CSC) resulted in significant alterations in the expression of oxidative stress-related genes (SEPP1, NCF2, SFTPD, CCL5, and PTGS1) in nasal epithelial cells. However, pretreatment with CUR and PEG-CUR mitigated these gene expression changes. Both treatments also reduced global DNA methylation, with PEG-CUR showing a more pronounced effect than CUR. Following the demonstration of the beneficial effects of PEG-CUR, we developed PEG-CUR-loaded dissolving microneedle patches (PEG-CUR-DMNPs) as a localized intranasal delivery platform designed to facilitate PEG-CUR delivery through rapid dissolution of the microneedle tips. The mechanical robustness and penetration capability of the patches were initially evaluated using Parafilm® and ex vivo rat dorsal skin models. To further confirm their appropriateness for intranasal use, PEG-CUR-DMNPs were subsequently tested on ex vivo sheep nasal mucosa to evaluate microneedle penetration and dissolution kinetics. Overall, these results indicate that PEG-CUR-DMNPs represent a promising approach for localized intranasal drug delivery targeting oxidative stress-related respiratory diseases.