Exosomes are endosome-derived nanovesicles produced by healthy as well as diseased cells. Their proteic, lipidic and nucleic acid composition is related to the cell of origin, and by vehiculating bioactive molecules they are involved in cell-to-cell signaling, both in healthy and pathologic conditions. Being nano-sized, non-toxic, biocompatible, scarcely immunogenic, and possessing targeting ability and organotropism, exosomes have been proposed as nanocarriers for their potential application in diagnosis and therapy. Among the different techniques exploited for exosome isolation, the sequential ultracentrifugation/ultrafiltration method seems to be the gold standard; alternatively, commercially available kits for exosome selective precipitation from cell culture media are frequently employed. To load a drug or a detectable agent into exosomes, endogenous or exogenous loading approaches have been developed, while surface engineering procedures, such as click chemistry, hydrophobic insertion and exosome display technology, allow for obtaining actively targeted exosomes. This review reports on diagnostic or theranostic platforms based on exosomes or exosome-mimetic vesicles, highlighting the diverse preparation, loading and surface modification methods applied, and the results achieved so far.

Ellagic acid, a polyphenolic compound present in fruit and berries, has recently been the object of extensive research for its antioxidant activity, which might be useful for the prevention and treatment of cancer, cardiovascular pathologies, and neurodegenerative disorders. Its protective role justifies numerous attempts to include it in functional food preparations and in dietary supplements, and not only to limit the unpleasant collateral effects of chemotherapy. However, ellagic acid use as a chemopreventive agent has been debated because of its poor bioavailability associated with low solubility, limited permeability, first pass effect, and interindividual variability in gut microbial transformations. To overcome these drawbacks, various strategies for oral administration including solid dispersions, micro and nanoparticles, inclusion complexes, self-emulsifying systems, and polymorphs were proposed. Here, we listed an updated description of pursued micro and nanotechnological approaches focusing on the fabrication processes and the features of the obtained products, as well as on the positive results yielded by in vitro and in vivo studies in comparison to the raw material. The micro and nanosized formulations here described might be exploited for pharmaceutical delivery of this active, as well as for the production of nutritional supplements or for the enrichment of novel foods.

Boron neutron capture therapy is a low-invasive cancer therapy based on the neutron fission process that occurs upon thermal neutron irradiation of ¹⁰B-containing compounds; this process causes the release of alpha particles that selectively damage cancer cells. Although several clinical studies involving mercaptoundecahydro-closo-dodecaborate and the boronophenylalanine–fructose complex are currently ongoing, the success of this promising anticancer therapy is hampered by the lack of appropriate drug delivery systems to selectively carry therapeutic concentrations of boron atoms to cancer tissues, allowing prolonged boron retention therein and avoiding the damage of healthy tissues. To achieve these goals, numerous research groups have explored the possibility to formulate nanoparticulate systems for boron delivery. In this review. we report the newest developments on boron vehiculating drug delivery systems based on nanoparticles, distinguished on the basis of the type of carrier used, with a specific focus on the formulation aspects.

Children affected by chronic liver disease exhibit impaired neurocognitive development and growth due to the low absorption and digestion of nutrients. Furthermore, malnutrition is an adverse prognostic factor in liver transplantation as it is associated with an increase in morbidity and mortality. D-α-tocopheryl-polyethylene-glycol-succinate (TPGS) is currently administered per os as a vitamin E source to improve children’s survival and well-being; however, TPGS alone does not reverse spinocerebellar degeneration and lipid peroxidation. To potentiate the effects of TPGS, we loaded micelles with resveratrol (RES), a natural polyphenol, with antioxidant and antiinflammatory activities, which has demonstrated protective action in the liver. Firstly, we investigated the suitability of TPGS to encapsulate RES in micelles by means of a phase-solubility study, then RES-TPGS formulations were prepared via solvent casting and solvent diffusion evaporation methods. RES-TPGS colloidal dispersions showed small mean diameters (12 nm), low polydispersity, and quite neutral Zeta potentials. The formulations showed a sustained drug release and a good drug loading capacity, further confirmed by infrared spectroscopy and differential scanning calorimetry. RES-TPGSs exhibited unaltered antioxidant activity compared to pristine RES via the DPPH assay and a significant reduction in toxicity compared to empty TPGS on HaCaT cells. Thus, RES-TPGS micelles may overcome the challenges of current liver disease therapy by providing more protective effects thanks to the antioxidant activity of RES and by reducing the surfactant toxicity on normal cells.

All-trans-retinoic acid (ATRA) represents the first-choice treatment for several skin diseases, including epithelial skin cancer and acne. However, ATRA’s cutaneous side effects, like redness and peeling, and its high instability limit its efficacy. To address these drawbacks and to improve ATRA solubilization, we prepared ATRA-loaded micelles (ATRA-TPGSs), by its encapsulation in D-α-tocopheryl-polyethylene-glycol-succinate (TPGS). First, to explore the feasibility of the project, a solubility study based on the equilibrium method was performed; then, six ATRA-TPGS formulations were prepared by the solvent-casting method using different TPGS amounts. ATRA-TPGSs showed small sizes (11–20 nm), low polydispersity, slightly negative zeta potential, and proved good encapsulation efficiency, confirmed by a chemometric-assisted Fourier transform infrared spectroscopy (FTIR) investigation. ATRA-TPGS stability was also investigated to choose the most stable formulation. Using Carbopol^® 980 as gelling agent, ATRA-TPGS-loaded gels were obtained and analyzed for their rheological profiles. Ex vivo release studies from ATRA-TPGSs were performed by Franz cells, demonstrating a permeation after 24 h of 22 ± 4 µ cm⁻². ATRA-TPGSs showed enhanced cytotoxic effects on melanoma cells, suggesting that these formulations may represent a valid alternative to improve patient compliance and to achieve more efficacious therapeutic outcomes.

Metformin is an antidiabetic drug which possesses antiproliferative activity in cancer cells when administered at high doses, due to its unfavorable pharmacokinetics. The aim of this work was to develop a pharmacological tool for the release of metformin in proximity of the tumor, allowing high local concentrations, and to demonstrate the in vivo antitumor efficacy after a prolonged metformin exposition. A 1.2% w/w metformin thermoresponsive parenteral formulation based on poloxamers P407 and P124, injectable at room temperature and undergoing a sol-gel transition at body temperature, has been developed and optimized for rheological, thermal and release control properties; the formulation is easily scalable, and proved to be stable during a 1-month storage at 5 °C. Using NOD/SCID mice pseudo-orthotopically grafted with MDA-MB-231/luc⁺ human breast cancer cells, we report that multiple administrations of 100 mg of the optimized metformin formulation close to the tumor site cause tissue accumulation of the drug at levels significantly higher than those observed in plasma, and enough to exert antiproliferative and pro-apoptotic activities. Our results demonstrate that this formulation is endowed with good stability, tolerability, thermal and rheological properties, representing a novel tool to be pursued in further investigations for adjuvant cancer treatment.