Since injection administration for diabetes is invasive, it is important to develop an effective transdermal method for insulin. However, transdermal delivery remains challenging owing to the strong barrier function of the stratum corneum (SC) of the skin. Here, we developed ionic liquid (IL)-in-oil microemulsion formulations (MEFs) for transdermal insulin delivery using choline–fatty acids ([Chl]­[FAs])comprising three different FAs (C18:0, C18:1, and C18:2)as biocompatible surface-active ILs (SAILs). The MEFs were successfully developed using [Chl]­[FAs] as surfactants, sorbitan monolaurate (Span-20) as a cosurfactant, choline propionate IL as an internal polar phase, and isopropyl myristate as a continuous oil phase. Ternary phase behavior, dynamic light scattering, and transmission electron microscopy studies revealed that MEFs were thermodynamically stable with nanoparticle size. The MEFs significantly enhanced the transdermal permeation of insulin via the intercellular route by compromising the tight lamellar structure of SC lipids through a fluidity-enhancing mechanism. In vivo transdermal administration of low insulin doses (50 IU/kg) to diabetic mice showed that MEFs reduced blood glucose levels (BGLs) significantly compared with a commercial surfactant-based formulation by increasing the bioavailability of insulin in the systemic circulation and sustained the insulin level for a much longer period (half-life > 24 h) than subcutaneous injection (half-life 1.32 h). When [Chl]­[C18:2] SAIL-based MEF was transdermally administered, it reduced the BGL by 56% of its initial value. The MEFs were biocompatible and nontoxic (cell viability > 90%). They remained stable at room temperature for 3 months and their biological activity was retained for 4 months at 4 °C. We believe SAIL-based MEFs will alter current approaches to insulin therapy and may be a potential transdermal nanocarrier for protein and peptide delivery.

Lipid-based biocompatible ionic liquids (LBILs) have attracted attention as carriers in transdermal drug delivery systems (TDDSs) because of their lipophilic character. In this study, we report the formulation of a peptide−LBIL complex microencapsulated in an oil phase as a potential carrier for the transdermal delivery of leuprolide acetate as a model hydrophilic peptide. The peptide−LBIL complexes were prepared via a water-in-oil emulsion composed of 1,2-dimyristoyl-sn-glycerol-3-ethyl-phosphatidylcholine (EDMPC), a fatty acid (stearic, oleic, and linoleic acid)-based LBIL, and cyclohexane followed by freeze-drying to remove the water and cyclohexane. Then, the peptide−LBIL complexes were nanodispersed and stabilized in isopropyl myristate (IPM) using sorbitol laurate (Span-20). Ionic-liquid-in-oil nanodispersions (IL/ O-NDs) were prepared with varying weight ratios of LBILs and Span-20 as the surfactant and the cosurfactant, respectively. Keeping the overall surfactant constant at 10 wt % in IPM, a 5:5 wt % ratio of surfactant (IL) and cosurfactant (Span-20) in the IL/O-NDs significantly (p < 0.0001) increased the physiochemical stability, drug-loading capacity, and drug encapsulation efficiency. The in vitro and in vivo peptide delivery across the skin was increased significantly (p < 0.0001) using IL/O-NDs, compared with non-ILtreated groups. Of all of the LBIL-based formulations, [EDMPC][Linoleate]/O-ND was considered the most preferable for a TDDS based on the pharmacokinetic parameters. The transdermal delivery flux with [EDMPC][Linoleate]/O-ND was increased 65-fold compared with the aqueous delivery vehicle. The IL/O-NDs were able to deform the lipid and protein arrangements of the skin layers to enhance the transdermal permeation of the peptide. In vitro and in vivo cytotoxicity studies of the IL/O-NDs revealed the biocompatibility of the LBIL-based formulations. These results indicated that IL/O-NDs are promising biocompatible carriers for lipid−peptide TDDSs.

Research on the role of reactive oxygen species (ROS) in the aging process has advanced significantly over the last two decades. In light of recent findings, ROS takes part in the aging process of cells along with contributing to various physiological signaling pathways. Antioxidants being cells' natural defense mechanism against ROS-mediated alteration, play an imperative role to maintain intracellular ROS homeostasis. Although the complete understanding of the ROS regulated aging process is yet to be fully comprehended, current insights into various sources of cellular ROS and their correlation with the aging process and age-related diseases are portrayed in this review. In addition, results on the effect of antioxidants on ROS homeostasis and the aging process as well as their advances in clinical trials are also discussed in detail. The future perspective in ROS-antioxidant dynamics on antiaging research is also marshaled to provide future directions for ROS-mediated antiaging research fields.

We report a new series of lipid-based biocompatible ionic liquids (LBILs) consisting of the long-chain phosphonium compound 1,2-dimyristoyl-sn-glycero-3-ethyl-phosphatidylcholine as the cation and the long-chain fatty acids stearic acid, oleic acid,...