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[Display omitted] • Novel PEGylated liposomes boost Idelalisib efficacy and lower toxicity. • Nanosized liposomes with prime entrapment and stability ready for preclinical tests. • Liposomal delivery augments Idelalisib's cytotoxicity in lymphoma B cells. • Idelalisib and nanotechnologies synergize for enhanced cancer therapy. New drugs and technologies are continuously developed to improve the efficacy and minimize the critical side effects of cancer treatments. The present investigation focuses on the development of a liposomal formulation for Idelalisib, a small-molecule kinase inhibitor approved for the treatment of lymphoid malignancies. Idelalisib is a potent and selective antitumor agent, but it is not indicated nor recommended for first-line treatment due to fatal and serious toxicities. Herein, liposomes are proposed as a delivery tool to improve the therapeutic profile of Idelalisib. Specifically, PEGylated liposomes were prepared, and their physicochemical and technological features were investigated. Light-scattering spectroscopy and cryo-transmission electron microscopy revealed nanosized unilamellar vesicles, which were proved to be stable in storage and in simulated biological fluids. The cytotoxicity of the liposome formulation was investigated in a human non-Hodgkin's lymphoma B cell line. Idelalisib was able to induce death of tumor cells if delivered by the nanocarrier system at increased efficacy. These findings suggest that combining Idelalisib and nanotechnologies may be a powerful strategy to increase the antitumor efficacy of the drug. [ABSTRACT FROM AUTHOR]

[Display omitted] Microfluidic mixing is recognized as a convenient method to produce liposomes for its scalability and reproducibility. Numerous studies have described the effect of process parameters such as flow rate ratios and total flow rate on size and size distribution of vesicles. In this work, we focused our attention on the effect of flow rate ratios on the encapsulation efficiency of liposomes, as we hypothesized that different amount of residual organic solvent could affect the retention of lipophilic drug molecules within the bilayer. In a further step, we investigated how the liposomes integrity and loading were impacted by different methods of solvent removal: direct dialysis and dilution & dialysis. Liposomes were prepared by rapidly mixing an ethanolic solution of lipids and a model drug with buffer in a herringbone micromixer, employing four different flow rate ratios (FRR, 4:1, 7:3, 3:2, 1:1). Quercetin, resveratrol and ascorbyl palmitate were used as model antioxidant drugs with different lipophilicity. Data showed that liposomes produced using lower flow rate ratios (i.e., with more residual ethanol) had lower encapsulation efficiencies as well as a more prominent loss of lipids from the bilayer following purification with direct dialysis. If the amount of residual ethanol was reduced to 5% (dilution & dialysis method), the lipids and drug leakage was prevented. Such effect was correlated with the drug aggregation propensity in different ethanol/water mixtures measured by molecular dynamics simulations. Overall, these results highlight the need to tailor the purification method basing on the molecular properties of the loaded drug to ensure high encapsulation and limit the waste of material. [ABSTRACT FROM AUTHOR]

[Display omitted] Vaccines based on protein antigens have numerous advantages over inactivated pathogens, including easier manufacturing and improved safety. However, purified antigens are weakly immunogenic, as they lack the spatial organization and the associated 'danger signals' of the pathogen. Formulating vaccines as nanoparticles enhances the recognition by antigen presenting cells, boosting the cell-mediated immune response. This study describes a nano-precipitation method to obtain stable protein nanoaggregates with uniform size distribution without using covalent cross-linkers. Nanoaggregates were formed via microfluidic mixing of ovalbumin (OVA) and lipids in the presence of high methanol concentrations. A purification protocol was set up to separate the nanoaggregates from OVA and liposomes, obtained as byproducts of the mixing. The nanoaggregates were characterized in terms of morphology, ζ-potential and protein content, and their interaction with immune cells was assessed in vitro. Antigen-specific T cell activation was over 6-fold higher for nanoaggregates compared to OVA, due in part to the enhanced uptake by immune cells. Lastly, a two-dose immunization with nanoaggregates in mice induced a significant increase in OVA-specific CD8+ T splenocytes compared to soluble OVA. Overall, this work presents for the first time the microfluidic production of lipid-stabilized protein nanoaggregates and provides a proof-of-concept of their potential for vaccination. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD), a small nonpsychoactive molecule derived from Cannabis sativa , exerts a variety of therapeutic actions, such as anti-inflammatory, antioxidant, and antibacterial. Epidiolex is the only FDA-approved medicine containing pure CBD as an oral solution for seizure-controlling therapy. Nevertheless, the oral bioavailability of CBD is challenging due to its physical-chemical properties such as low solubility in water and high first-pass metabolism. By contrast, inhaled CBD has shown faster absorption and higher plasma concentration. Nanosuspensions represent an optimal strategy to obtain an effective aerosolizable formulation of poorly soluble drugs. In this study, a CBD nanosuspension was produced using a bottom-up technique, namely, a solvent/antisolvent nanoprecipitation. The obtained system was thoroughly characterized in terms of dimensions and ζ potential, nanocrystal morphology, and solid-state properties. The formulation was composed of homogeneously dispersed nanocrystals of approximately 88 nm, with a faster dissolution profile compared with the raw drug and the coarse suspension. The nebulization tests carried out using a Next Generation Impactor (NGI, Apparatus E Ph. Eu) highlighted optimal aerodynamic properties with high values of fine particle fraction and MMAD < 5 μm. Finally, the safety of the nanomedicine was assessed on human pulmonary cells demonstrating excellent biocompatibility.