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, β-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.

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.

Background/Objectives: Salvia officinalis L. is widely used in food supplements, particularly those intended to support women’s health and alleviate menopausal vasomotor symptoms. However, the extent to which estrogen receptor signaling contributes to its reported clinical benefits remains unclear. Therefore, evaluating its potential endocrine activity is a key aspect of its toxicological characterization and overall safety assessment. The present study aimed to investigate the potential estrogenic effects of a standardized Italian Salvia officinalis L. extract (Salvira™), as well as its biological effects on estrogen-responsive breast cancer cells (MCF-7). Methods: In vitro enzymatic assays and estrogen receptor alpha (ERα) agonist- and antagonist-mode experiments were performed to assess its ability to modulate ERα signaling. Moreover, cell viability, proliferation, and clonogenic capacity were assessed in MCF-7 cells following exposure to increasing concentrations of the extract. Results: The extract did not exhibit estrogenic activity in all experimental dose–response assays. In MCF-7 cells, treatment with the sage extract did not produce an overall effect on cell viability or proliferative capacity. Moreover, no impairment of long-term clonogenic potential was observed at the tested concentrations. Conclusions: Under the experimental conditions investigated, the present findings suggest that the standardized Salvia officinalis L. extract showed no evidence of estrogenic activity and did not induce relevant ERα-mediated biological effects in estrogen-responsive MCF-7 cells. These findings contribute to the characterization of the endocrine safety profile of the extract, supporting its safe use as an ingredient in food supplements.

Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide and an endocannabinoid-related lipid that has been extensively studied for its analgesic, immunomodulatory, antimicrobial, and anti-inflammatory properties. It has demonstrated efficacy in various applications and is currently utilized as a nutraceutical for its antinociceptive, neuroprotective, and immunomodulatory effects, particularly in supporting brain and joint health and in mitigating inflammatory processes. Background/Objectives: Despite its significant therapeutic potential, the clinical effectiveness of PEA is limited by its poor water solubility and, consequently, low oral bioavailability. Additionally, degradation in the acidic gastrointestinal environment further compromises its absorption. To address these challenges, several technological strategies have been explored to improve its pharmacokinetic profile, including conventional micronization and ultra-micronization techniques. The objective of this study was to characterize a novel liposomal formulation based on PEA and evaluate its intestinal permeation and absorption. Methods: Comparative permeation studies of PEA were conducted using ex vivo models to evaluate its absorption characteristics across gastrointestinal mucosae. The experiments were performed in a Franz diffusion cell system using a porcine colon mucosa in two physiologically relevant media: Simulated Gastric Fluid (SGF) and Fasted State Simulated Intestinal Fluid (FaSSIF). Results: Liposomal PEA showed a more efficient and continuous release over time, reaching higher concentrations of PEA permeated through the membrane. Conclusions: Our findings demonstrate a significant improvement in PEA’s permeability and absorption in an ex vivo simulated gastrointestinal environment. Liposomal PEA appears to be more affine to biological membranes. These results suggest that liposomal PEA may represent a promising therapeutic strategy for managing chronic pain and inflammatory conditions such as chronic pelvic pain.