On-demand photoresponsive liposomes-in-gel to prevent UV light-induced cellular damage

To achieve prolonged and on-demand sunscreen effects, liposomes containing a lipid with a photoresponsive azobenzene moiety (BisAzo-PC) were constructed and photoprotective effects were demonstrated on a fibroblast cell line. The synthesis of BisAzo-PC was confirmed by FTIR, LC–MS, and ¹H NMR. Photoresponsive and thermal properties of BisAzo-PC were studied, revealing a rapid UV-induced trans–cis isomerization and a slow cis–trans isomerisation. BisAzo-PC liposomes (∼120 nm, optimal size for dermal delivery) were prepared and loaded with both hydrophilic (benzophenone-4) and lipophilic (octocrylene) UV filters, achieving high entrapment efficiencies (24.8% and 99.9%) and loading capacities (12.2% and 9.9%, w/w), respectively. The liposomes demonstrated rapid UV filter release triggered by UV irradiation (365 nm), with an extended-release period of 6 hours. Liposomes incorporated into a hydroxypropyl methylcellulose (HPMC)–polyvinylpyrrolidone (PVP)-based bioadhesive hydrogel provided a universal sun protection factor (uSPF) value of 38.1 ± 1.1, exceeding that of a commercial sunscreen of 32.3 ± 0.1. The liposome-in-gel reproducibly protected fibroblasts from UV exposure and reduced intracellular reactive oxygen species (ROS) by 72% for up to 6 hours, accompanied by a 45% reduction of the lipid peroxidation marker malondialdehyde (MDA) and antioxidant enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). The results highlight the potential of photoresponsive liposomes-in-gel with extended photoprotective properties to be further translated into a long-acting sunscreen by addressing the main concerns of conventional sunscreens, reducing the need for frequent applications and the risk of systemic absorption of UV filters.