Formulation Strategies to Improve Oral Bioavailability of Ellagic Acid

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

A new microdispersed albumin derivative potentially useful for radio-guided surgery of occult breast cancer lesions

This paper describes a new nuclear imaging agent, 2-(4-isothiocyanatobenzyl) 121,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid of human albumin (HAC), potentially suitable for application in the Radio-guided Occult Lesion Localization (ROLL) of non-palpable mammalian cancerous lesions, as a tool to overtake the short radio-signal half-life of the technetium-99m based radiopharmaceutical currently used. This conjugate is a microsized powder aggregate, water-insoluble between pH 3 and 8.5, obtained by conjugating the protein with the macrocyclic chelating agent DOTA through a one-pot reaction in aqueous medium. The product has been fully characterized and is stable to the thermal conditions adopted for labeling; after radiolabeling with longer half-life radionuclides such as 177 Lu or 111 In, it has shown radiochemical purity (RCP) >90% and resulted stable when stored in saline or plasma for 6 days at 37 \ub0C. A \u3bcPET/CT study, performed in vivo on adult female rats, showed that the radioactivity of HAC labeled with 64 Cu remained located in the mammary glands for at least 40 h, without diffusion or drainage in healthy tissues or in the lymphatic circulation. This new imaging agent might make the ROLL procedure more accessible, safe and flexible, promoting a significant time and cost reduction of this intervention. Moreover, HAC might also be used in other radio-guided surgical procedures in oncology

Neuroinflammation in Aged Brain: Impact of the Oral Administration of Ellagic Acid Microdispersion

The immune system and the central nervous system message each other to preserving central homeostasis. Both systems undergo changes during aging that determine central age-related defects. Ellagic acid (EA) is a natural product which is beneficial in both peripheral and central diseases, including aging. We analyzed the impact of the oral administration of a new oral ellagic acid micro-dispersion (EAm), that largely increased the EA solubility, in young and old mice. Oral EAm did not modify animal weight and behavioral skills in young and old mice, but significantly recovered changes in "ex-vivo, in vitro" parameters in old animals. Cortical noradrenaline exocytosis decreased in aged mice. EAm administration did not modify noradrenaline overflow in young animals, but recovered it in old mice. Furthermore, GFAP staining was increased in the cortex of aged mice, while IBA-1 and CD45 immunopositivities were unchanged when compared to young ones. EAm treatment significantly reduced CD45 signal in both young and old cortical lysates; it diminished GFAP immunopositivity in young mice, but failed to affect IBA-1 expression in both young and old animals. Finally, EAm treatment significantly reduced IL1beta expression in old mice. These results suggest that EAm is beneficial to aging and represents a nutraceutical ingredient for elders

Farmaci biotecnologici nel trattamento dell'Artrite Reumatoide: Aspetti farmacoeconomici nella gestione del paziente in remissione clinica

Le malattie reumatiche hanno un forte impatto sociale per l\u2019elevata incidenza, i costi economici e la riduzione della qualit\ue0 della vita delle persone afflitte da questa patologia, che raccoglie oltre 100 diverse malattie. L\u2019Organizzazione Mondiale della Sanit\ue0 (OMS) indica le malattie reumatiche come la prima causa di dolore e disabilit\ue0 in Europa e ricorda che queste, da sole, rappresentano la met\ue0 delle malattie croniche che colpiscono la popolazione al di sopra dei 65 anni. Alla luce di queste motivazioni, l\u2019OMS e l\u2019ONU hanno dedicato il decennio 2000/2010 alla prevenzione e al trattamento delle malattie muscolo-scheletriche e reumatiche (2000/2010 bone and joint decade o BJD). Le malattie considerate dalla BJD 2000-2010 sono quelle articolari (artrite reumatoide, artrosi, ecc), l\u2019osteoporosi, le lombalgie, le malattie della colonna vertebrale, i traumi degli arti, e le malattie muscoloscheletriche dei bambini. In questa testo sono raccolti e analizzati i principali farmaci biotecnologici utilizzati su una coorte di 105 pazienti affetti da artrite reumatoide in remissione ed l loro costo per il servizio sanitario confrontando la modalit\ue0 di terapia continua con quella discontinua

Exosomes and Extracellular Vesicles as Emerging Theranostic Platforms in Cancer Research

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

Constituents of Cupuliferae. XVII. Triterpene saponins and flavonoids from Quercus laurifolia Michx.

In addition to fourteen known glycosides from leaves of Quercus laurifolia Michx., a new acylated triterpene soponin has been isolated and identified as 3-O-galloyl-28-beta-D-glucopyranosyl diester of the 2alpha,3beta,19alpha,23-tetrahydroxyurs-12-ene-28-oic acid (1). The structure of the previously described alpha-D-glucopyranosyl ester of the 2alpha,3beta,19alpha,23-tetrahydroxyurs-12-ene-28-oic acid was revised to beta-D-glucopyranosyl ester of the 2alpha,3beta,19alpha,23-tetrahydroxyurs-12-ene-28-oic acid (2)