The aim of the present study is to evaluate the stability of DMPC:Pluronic F-127 and DPPC:Pluronic F-127 liposomes, both with and without incorporated quercetin. Quercetin belongs to the class of flavonoids and has shown antioxidant, antiviral, anti-inflammatory, anti-cancer, and antimicrobial activities. Dynamic light scattering, electrophoretic light scattering, and differential scanning calorimetry (DSC) were utilized to investigate the cooperative behavior between liposomal components and its effect on stability. All formulations were stored at 4 °C and 25 °C and studied over 42 days. Furthermore, the interaction of the final formulations with serum proteins was assessed to evaluate the potential of Pluronic F-127 as a stabilizer in these liposomal nanosystems. This study highlights the impact of DSC in preformulation evaluations by correlating thermal behavior with quercetin incorporation and variations in size and the polydispersity index. According to the results, quercetin increased the fluidity and stability of liposomal nanosystems, while Pluronic F-127 was not sufficient for effective steric stabilization. Additionally, DSC thermograms revealed the integration of Pluronic F-127 into lipid membranes and showed phase separation in the DMPC nanosystem. In conclusion, the results indicate that the DPPC:Pluronic F-127:quercetin nanosystem exhibited the desired physicochemical and thermotropic properties for the effective delivery of quercetin for pharmaceutical purposes.

Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, affect a wide variety of the population and pose significant challenges with progressive and irreversible neural cell loss. The limitations of brain-targeting therapies and the unclear molecular mechanisms driving neurodegeneration hamper the possibility of developing successful treatment options. Thus, nanoscale drug delivery platforms offer a promising solution. This paper explores and compares lipidic nanoparticles, extracellular vesicles (EVs), and hybrid liposomal–EV nanoplatforms as advanced approaches for targeted delivery to combat neurodegeneration. Lipidic nanoparticles are well-characterized platforms that allow multi-drug loading and scalable production. Conversely, EVs offer the ability of selectively targeting specific tissues and high biocompatibility. The combination of these two platforms in one could lead to promising results in the treatment of neurodegeneration. However, many issues, such as the regulatory framework, remain to be solved before these novel products are translated into clinical practice.

The aim of the present study is the development, physicochemical characterization, and in vitro cytotoxicity evaluation of both empty and quercetin-loaded HSPC (hydrogenated soy phosphatidylcholine) liposomes, GMO (glyceryl monooleate) liquid crystalline nanoparticles, and PHYT (phytantriol) liquid crystalline nanoparticles. Specifically, HSPC phospholipids were mixed with different non-ionic surfactant molecules (Tween 80 and/or Span 80) for liposomal formulations, whereas both GMO and PHYT lipids were mixed with Span 80 and Tween 80 as alternative stabilizers, as well as with Poloxamer P407 in different ratios for liquid crystalline formulations. Subsequently, their physicochemical properties, such as size, size distribution, and ζ-potential were assessed by the dynamic and electrophoretic light scattering (DLS/ELS) techniques in both aqueous and biological medium with serum proteins. The in vitro biological evaluation of the empty nanosystems was performed by using the MTT cell viability and proliferation assay. Finally, the entrapment efficiency of quercetin was calculated and the differences between the two different categories of lipidic nanoparticles were highlighted. According to the results, the incorporation of the non-ionic surfactants yields a successful stabilization and physicochemical stability of both liposomal and liquid crystalline nanoparticles. Moreover, in combination with an appropriate biosafety in vitro profile, increased encapsulation efficiency of quercetin was achieved. Overall, the addition of surfactants improved the nanosystem’s stealth properties. In conclusion, the results indicate that the physicochemical properties were strictly affected by the formulation parameters, such as the type of surfactant.

This study investigates the influence of phospholipid saturation by comparing hydrogenated soy phosphatidylcholine (HSPC) and egg yolk phosphatidylcholine (EPC) on the physicochemical characteristics, colloidal stability, drug release behavior and antioxidant activity of quercetin-loaded ceramide-containing liposomes for topical delivery. Liposomes composed of EPC:Cer:Que and HSPC:Cer:Que were prepared by thin-film hydration followed by sonication. The nanosystems were studied for particle size, polydispersity index, ζ-potential, and entrapment efficiency. Colloidal stability was evaluated under mechanical stress, accelerated aging, and long-term storage, while in vitro drug release, drug retention, and antioxidant activity were assessed under simulated skin conditions. Incorporation of ceramides into EPC bilayer reduced stability issues associated with unsaturated phospholipids and maintained a fluid structure, promoting drug release. Both formulations exhibited enhanced colloidal stability with EPC-based liposomes maintaining their properties at all conditions, whereas HSPC-based liposomes showed increased particle size following mechanical stress. HSPC-based liposomes demonstrated higher quercetin entrapment efficiency (63 ± 5%), improved retention over time (75% at 90 days), and a more sustained release (45% at 480 min). EPC-based ceramide-containing liposomes exhibited faster release (50% at 240 min), resulting in greater antioxidant activity as indicated by DPPH assay (0.474 ascorbic acid equivalents), while FRAP assay results were comparable for both formulations (0.012 Fe ²⁺ equivalents), indicating consistent ferric reducing potential after release. These findings highlight the significance of phospholipid composition in liposome behavior and provide insights into the design of stable and effective ceramide-containing nanosystems for topical delivery of poorly water-soluble compounds such as quercetin, with potential applications in managing photoaging, inflammation, and wound healing. Graphical Abstract

Cannabidiol (CBD) is a highly lipophilic molecule characterized by low oral bioavailability, primarily due to its limited solubility and extensive first-pass metabolism. This study aims to improve apparent solubility of cannabidiol through the development of liposomal and self-microemulsifying drug delivery systems (SMEDDS). Liposomes incorporating ω-3 fatty acids, and SMEDDS formulations were prepared and assessed regarding their hydrodynamic diameter, polydispersity index, and z-potential. Furthermore, tablets were developed from lyophilized powders and encapsulated into enteric-coated capsules to protect CBD from degradation in the acidic environment of the stomach, minimizing conversion to unwanted metabolites and ensuring greater stability. Both liposomes and SMEEDS formulations showed significantly faster dissolution rate (81 % for L1, 94 % for L2, 69 % for S1 and 66 % for S2) compared to 28 % of pure CBD tablet formulation within 720 min in simulated intestinal fluid conditions (pH = 6.8). Lyophilized formulations were evaluated by Scanning Electron Microscopy (SEM), and powder X-ray diffraction (XRPD) confirming the amorphous or molecularly dissolved state of CBD within the formulations. The overall antioxidant activity of CBD was retained after incorporation into liposomes and SMEDDS as measured by DPPH assay. Overall, these findings indicate that liposomes and SMEDDS are promising oral drug delivery systems for enhancing the solubility of CBD.