Factorial design-guided optimization of liposome/lipoplex fabrication using microfluidic chip technology for anti-fibrotic wound healing
Journal of Drug Delivery Science and Technology, cilt.125, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 125
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.jddst.2026.108694
- Dergi Adı: Journal of Drug Delivery Science and Technology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE
- Anahtar Kelimeler: Burn, Factorial design, Lipoplex, Liposome, Microfluidics, miR-132, TGF-β3
- Hacettepe Üniversitesi Adresli: Evet
Özet
Although mortality rates in burn injuries have decreased, hypertrophic scar formation following burns reduces the quality of life and social participation of individuals. Scar formation can lead to secondary consequences such as neuropathic pain, surface irregularities, tissue stiffness, and disabling contractures. This study aimed to promote scarless healing and accelerate the healing process of burn wounds by reducing persistent inflammation through the anti-inflammatory effect of the miR-132 mimic (synthetic double-stranded miRNA-132) and directing angiogenesis in burn tissue through its pro-angiogenic effect; and by suppressing the scar tissue formation potential of TGF-β1 through the antifibrotic effect of TGF-β3. For targeted delivery while maintaining biological activity, TGF-β3 was encapsulated in DOTMA/DOPC/CHOL-based cationic liposome, while miR-132 was electrostatically complexed to form lipoplex formulations. To enhance transfection efficiency, the systems were PEGylation-treated and optimized with a particle size of 100–200 nm and a zeta potential equal to or greater than +40 mV. In vitro evaluations were conducted in mouse dermal fibroblast cell lines, where fibrosis was induced by TGF-β1, and the efficacy of the formulations in preventing fibrosis was determined at the gene and protein levels using real-time PCR and ELISA methods, respectively. In the in vitro fibrosis model, combined treatment optimized the COL1/COL3 ratio and generated a balanced anti-fibrotic response at collagen, MMP13, MMP9, RASA1, and cytokine levels. Overall, these results suggest that dual-acting liposomes/lipoplexes containing miR-132 and TGF-β3 demonstrate a promising in vitro approach for burn wound healing.