Metformin loaded cholesterol-lysine conjugate nanoparticles: A novel approach for protecting HDFs against UVB-induced senescence

• Published in: International journal of pharmaceutics 2020-08, Vol.586, p.119603-119603, Article 119603
• Main Authors: Nayeri Rad, Amirhossein, Shams, Golnaz, Safdarian, Mehdi, Khorsandi, Layasadat, Grillari, Johannes, Sharif Makhmalzadeh, Behzad
• Format: Article
• Language: English
• Subjects: Human dermal fibroblast; Metformin; Senescence; Solid lipid nanoparticles; Topical; UVB
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.119603

[Display omitted] •Lysine was conjugated with cholesterol to increase hydrogen bonding capacity and hydrophilicity of cholesterol.•Synthesized Cholesterol-Lysine conjugate was used as lipid in formation of Solid lipid nanoparticles to increase entrapment efficiency of metformin, which is a hydrophilic drug.•Solid lipid nanoparticles containing metformin showed zero order release profile with capability to cross epidermal barriers.•Solid lipid nanoparticles of metformin could attenuate senescence associated markers including p16 expression and SA- β-gal activity in UVB induced senescent HDFs. Cellular senescence is one of the hallmarks of aging. Since senescence of dermal fibroblasts has been reported in vivo, reduction of the deleterious effects of these cells, has been considered an important intervention to counteract skin aging. Promising anti-aging effect of metformin has been reported. However, permeation of metformin due to its high hydrophilicity through skin epidermal barriers is limited. In this study, solid lipid nanoparticles (SLNs) of metformin were designed with the newly synthesized cholesterol-lysine conjugate as lipid for topical delivery of metformin. Characterization of SLNs strongly confirmed the effect of cholesterol-lysine conjugate on increasing entrapment of metformin. The designed SLNs with particle size of 283 nm and spherical morphology represented controlled drug release up to 18 days. Fluorescent tracking of SLNs on mice skin samples showed an increase in epidermal penetration. SLNs containing metformin showed anti-senescence effects on UVB-induced senescence of human dermal fibroblasts, this effect was confirmed by senescence-associated β-galactosidase staining, RT q-PCR and cell cycle analyses. Furthermore, our drug-free SLNs showed anti-senescence effects, suggesting that they can be a suitable carrier for phytochemicals with anti-aging effect or other hydrophilic compounds which have constraints permeating skin.