Nano-drug delivery systems provide targeted solutions for addressing various drug delivery challenges, leveraging nanotechnology to enhance drug solubility and permeability. Liposomes, explored for several decades, face hurdles, especially in oral delivery. Bile-acid stabilized vesicles (bilosomes) are flexible lipid vesicles, composed of phospholipids or other surfactants, along with amphiphilic bile salts, and they show superior stability and pharmacokinetic behavior in comparison to conventional vesicular systems (liposomes and niosomes). Bilosomes enhance skin penetration, fluidize the stratum corneum, and improve drug stability. In oral applications, bilosomes overcome drawbacks, offering improved bioavailability, controlled release, and reduced side effects. Vaccines using bilosomes demonstrate efficacy, and bilosomes for intranasal, inhalation, ocular, and buccal applications enhance drug delivery, offering targeted, efficient, and controlled activities. Formulations vary based on active substances and optimization techniques, showcasing the versatility and potential of bilosomes across diverse drug delivery routes. Therefore, the aim of this comprehensive review was to critically explore the state-of-the-art of bilosomes in drug delivery and potential therapeutic applications.

Despite its beneficial pharmacological effects in the brain, partly by modulating inositol phosphate multikinase (IPMK) activity, the therapeutic use of quercetin is limited due to its poor solubility, low oral bioavailability, and low permeability through the blood–brain barrier (BBB). We aimed to identify quercetin analogues with improved BBB permeability and preserved binding affinities towards IPMK and to identify the molecular characteristics required for them to permeate the BBB. Binding affinities of quercetin analogues towards IPMK were determined by molecular docking. Principal component analysis (PCA) was applied to identify the molecular descriptors contributing to efficient permeation through the BBB. Among 34 quercetin analogues, 19 compounds were found to form more stable complexes with IPMK, and the vast majority were found to be more lipophilic than quercetin. Using two distinct in silico techniques, insufficient BBB permeation was determined for all quercetin analogues. However, using the PCA method, the descriptors related to intrinsic solubility and lipophilicity (logP) were identified as mainly responsible for clustering four quercetin analogues (trihydroxyflavones) with the highest BBB permeability. The application of PCA revealed that quercetin analogues could be classified with respect to their structural characteristics, which may be utilized in further analogue syntheses and lead optimization of BBB-penetrating IPMK modulators as neuroprotective agents.

Resveratrol exerts neuroprotective effects that are not only due to anti inflammatory and antioxidant activity but also by launched biogenesis via sirtuin-1 (SIRT1) protein that protects cells from oxidative stress. Resveratrol has low bioavailability due to low aqueous solubility and rapid metabolism. To improve the pharmacological profile, one of the strategies is the structural modification and selecting an analogue that would activate SIRT1 and improve pharmacokinetics. The aim was to examine the neuroprotective potential of resveratrol analogues through the analysis of the binding affinity to the sirtuin-1 receptor and with improved permeability through the blood-brain barrier. 15 of them have a higher affinity for the target. Four analogues are characterized by better properties including both higher permeability and higher binding affinity for SIRT1 compared to resveratrol. The selected compounds are assumed to have better bioavailability and CNS distribution, and further studies are proposed to confirm their effects and use as neuroprotective agents.