Anionic Methacrylate Copolymer Microparticles for the Delivery of Myo-Inositol Produced by Spray-Drying: In Vitro and In Vivo Bioavailability.

In this study, a new micro delivery system based on an anionic methacrylate copolymer, able to improve the biological response of myo-inositol by daily oral administration, was manufactured by spray-drying. It has an ideal dose form for oral administration, with an experimental drug loading (DL)% of 14% and a regulated particle size of less than 15 µm. The new formulation features an improvement on traditional formulations used as a chronic therapy for the treatment of polycystic ovary syndrome. The microparticles' release profile was studied and ex vivo porcine intestinal mucosa permeation experiments were performed to predict potential improvements in oral absorption. Batch n. 3, with the higher Eudragit/MI weight ratio (ratio = 6), showed the best-modified release profiles of the active ingredient, ensuring the lowest myo-inositol loss in an acidic environment. The in vivo evaluation of the myo-inositol micro delivery system was carried out in a rat animal model to demonstrate that the bioavailability of myo-inositol was increased when compared to the administration of the same dosage of the pure active ingredient. The AUC and Cmax of the loaded active molecule in the micro delivery system was improved by a minimum of 1.5 times when compared with the pure substance, administered with same dosage and route. Finally, the increase of myo-inositol levels in the ovary follicles was assessed to confirm that a daily administration of the new formulation improves myo-inositol concentration at the site of action, resulting in an improvement of about 1.25 times for the single administration and 1.66 times after 7 days of repeated administration when compared to pure MI.

Gastro-Resistant Microparticles Produced by Spray-Drying as Controlled Release Systems for Liposoluble Vitamins.

In the present study, gastro-resistant microparticles (MPs) were produced using the spray-drying technique as controlled-release systems for some model liposoluble vitamins, including retinyl-palmitate, retinyl-acetate, ß-carotene, cholecalciferol and α-tocopherol. The gastroprotective action of three different gastro-resistant excipients, the anionic methacrylic copolymer (Eudraguard®® Biotic, E1207), the cellulose acetate phthalate (CAP) and whey proteins (WPs), was compared. The latter was used to produce a novel delivery system manufactured with only food-derived components, such as milk, and showed several improvements over the two synthetic gastro-resistant agents. Scanning electron microscopy (SEM) images showed a quite homogeneous spherical shape of all microparticle batches, with an average diameter between 7 and 15 µm. FTIR analysis was used to evaluate the effective incorporation of vitamins within the microparticles and the absence of any degradation to the components of the formulation. The comparison graphs of differential scanning calorimetry (DSC) confirmed that the spray drying technique generates a solid in which the physical interactions between the excipients and the vitamins are very strong. Release studies showed a prominent pH-controlled release and partially a delayed-release profile. Ex vivo permeation studies of retinyl palmitate, retinyl acetate and α-tocopherol revealed greater transmucosal permeation capacity for microparticles produced with the WPs and milk.

Discovery of new heterocycles with activity against human neutrophile elastase based on a boron promoted one-pot assembly reaction.

Herein we demonstrate for the first time that a boron promoted one-pot assembly reaction may be used to discover novel enzyme inhibitors. Inhibitors for HNE were simply assembled in excellent yields, high diastereoselectivities and IC50 up to 1.10 µM, based on components like salicylaldehyde, aryl boronic acids and amino acids. The combination of synthetic, biochemical, analytical and theoretical studies allowed the identification of the 4-methoxy or the 4-diethyl amino substituent of the salicylaldehyde as the most important recognition moiety and the imine alkylation, lactone ring opening as key events in the mechanism of inhibition.

Four-component assembly of chiral N-B heterocycles with a natural product-like framework.

The dative N-B bond was used to simply assemble heterocycles with a skeleton akin to the 5-oxofuro[2,3-b]furan motif. Twenty-five new N-B heterocycles were prepared via a highly efficient one-pot four-component reaction in yields and diastereoselectivities up to 95% and >97%, respectively. Several reaction intermediates were discovered using electrospray ionization mass spectroscopy which set the basis for the mechanism elucidation using DFT calculations.