Exosomes are naturally derived information carriers that present interest as drug delivery systems. However, their vague cargo and isolation difficulties hinder their use in clinical practice. To overcome these limitations, we developed exosome-like nanoparticles, consisted of the main lipids of exosomes, using two distinct methods: thin-film hydration and 3D-printed microfluidics. Our novel microfluidic device, fabricated through digital light processing printing, demonstrated a favorable architecture to produce exosome-like nanoparticles. We compared these two techniques by analyzing the physicochemical characteristics (size, size distribution, and ζ-potential) of both unloaded and genistein-loaded exosome-like nanoparticles, using dynamic and electrophoretic light scattering. Our findings revealed that the presence of small lipophilic molecules, cholesterol and/or genistein, influenced the characteristics of the final formulations differently based on the development approach. Regardless of the initial differences of the formulations, all exosome-like nanoparticles, whether loaded with genistein or not, exhibited remarkable colloidal stability over time. Furthermore, an encapsulation efficiency of over 87% for genistein was achieved in all cases. Additionally, thermal analysis uncovered the presence of metastable phases within the membranes, which could impact the drug delivery efficiency. In summary, this study provides a comprehensive comparison between conventional and innovative methods for producing complex liposomal nanosystems, exemplified by exosome-like nanoparticles.

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.