Development of pH-dependent systems for colon delivery of natural active ingredients is an attractive area of research in the field of nutraceutical products. This study was focused on Eudraguard® resins, that are methacrylate copolymers approved as “food grade” by European Commission and useful for the production of food supplements. In particular, Eudraguard® Biotic (EUG-B), characterized by a pH-dependent solubility and Eudraguard® Control (EUG-C), whose chemical properties support a prolonged release of the encapsulated compounds, were tested. To obtain EUG microparticles, different preparation techniques were tested, in order to optimize the preparation method and observe the effect upon drug encapsulation and specific colonic release. Unloaded microparticles were initially produced to evaluate the influence of polymer characteristics on the formulation process; subsequently microparticles loaded with quercetin (QUE) as a low solubility model drug were prepared. The characterization of microparticles in the solid-state (FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry) indicated that QUE was uniformly dispersed in a non-crystalline state in the polymeric network, without strong signs of chemical interactions. Finally, to assess the ability of EUG-C and EUG-B to control the drug release in the gastric environment, and to allow an increased release at a colonic level, suitable in vitro release tests were carried out by simulating the pH variations along the gastro-intestinal tract. Among the evaluated preparation methods, those in which an aqueous phase was not present, and in particular the emulsion-solvent evaporation method produced the best microparticle systems. The in vitro tests showed a limited drug release at a gastric level and a good specific colon release.

The greatest challenge associated with topical drug delivery for the treatment of diseases affecting the posterior segment of the eye is to overcome the poor bioavailability of the carried molecules. Nanomedicine offers the possibility to overcome obstacles related to physiological mechanisms and ocular barriers by exploiting different ocular routes. Functionalization of nanosystems by fluorescent probes could be a useful strategy to understand the pathway taken by nanocarriers into the ocular globe and to improve the desired targeting accuracy. The application of fluorescence to decorate nanocarrier surfaces or the encapsulation of fluorophore molecules makes the nanosystems a light probe useful in the landscape of diagnostics and theranostics. In this review, a state of the art on ocular routes of administration is reported, with a focus on pathways undertaken after topical application. Numerous studies are reported in the first section, confirming that the use of fluorescent within nanoparticles is already spread for tracking and biodistribution studies. The first section presents fluorescent molecules used for tracking nanosystems’ cellular internalization and permeation of ocular tissues; discussions on the classification of nanosystems according to their nature (lipid-based, polymer-based, metallic-based and protein-based) follows. The following sections are dedicated to diagnostic and theranostic uses, respectively, which represent an innovation in the ocular field obtained by combining dual goals in a single administration system. For its great potential, this application of fluorescent nanoparticles would experience a great development in the near future. Finally, a brief overview is dedicated to the use of fluorescent markers in clinical trials and the market in the ocular field.

Diosmin is a flavonoid with a great variety of biological activities including antioxidant and anti-inflammatory ones. Its cytoprotective effect in retinal pigment epithelium cells under high glucose conditions makes it a potential support in the treatment of diabetic retinopathy. Despite its benefits, poor solubility in water reduces its potential for therapeutic use, making it the biggest biopharmaceutical challenge. The design of diosmin-loaded nanocarriers for topical ophthalmic application represents a novelty that has not been yet explored. For this purpose, the response surface methodology (RSM) was used to optimize nanostructured lipid carriers (NLCs), compatible for ocular administration, to encapsulate diosmin and improve its physicochemical issues. NLCs were prepared by a simple and scalable technique: a melt emulsification method followed by ultrasonication. The experimental design was composed of four independent variables (solid lipid concentration, liquid lipid concentration, surfactant concentration and type of solid lipid). The effect of the factors was assessed on NLC size and PDI (responses) by analysis of variance (ANOVA). The optimized formulation was selected according to the desirability function (0.993). Diosmin at two different concentrations (80 and 160 µM) was encapsulated into NLCs. Drug-loaded nanocarriers (D-NLCs) were subjected to a physicochemical and technological investigation revealing a mean particle size of 83.58 ± 0.77 nm and 82.21 ± 1.12 nm, respectively for the D-NLC formulation prepared with diosmin at the concentration of 80 µM or 160 µM, and a net negative surface charge (−18.5 ± 0.60 and −18.0 ± 1.18, respectively for the two batches). The formulations were analyzed in terms of pH (6.5), viscosity, and adjusted for osmolarity, making them more compatible with the ocular environment. Subsequently, stability studies were carried out to assess D-NLC behavior under different storage conditions up to 60 days, indicating a good stability of NLC samples at room temperature. In vitro studies on ARPE-19 cells confirmed the cytocompatibility of NLCs with retinal epithelium. The effect of D-NLCs was also evaluated in vitro on a model of retinal inflammation, demonstrating the cytoprotective effect of D-NLCs at various concentrations. RSM was found to be a reliable model to optimize NLCs for diosmin encapsulation.

Background: Colon delivery systems are designed for the oral delivery of active compounds in the large intestine. Food-grade copolymers Eudraguard® Biotic (EUGB) and control (EUGC) have been investigated to develop colloidal systems loading natural active ingredients. Methods: In this study, we evaluated the degradation process of these matrices in simulated gastric, intestinal and colonic conditions. Microparticles made of EUGB and EUGC, alone or in combination, were loaded with the model compound resveratrol (RSV). A parallel study was performed on in vitro RSV release and SEM analysis of microparticles kept at different pH values. Results: All systems ensured a limited gastric release of RSV (below 20%), presenting only small pores on the surface of microparticles treated with simulated gastric fluid. EUGB microparticles showed the maximum release in simulated colon fluid (SCF), showing a complete dissolution of the microparticle matrix. The EUGC-based system allowed a prolonged release of RSV over time, and in SCF, it showed only partial degradation. Using mixed EUGB/EUGC matrices, a prolonged RSV release was observed along the intestinal tract. Conclusion: Overall, EUGB and EUGC copolymers were able to modulate and localize the release of entrapped cargo in the small intestine and colon. They could have interesting applications in treating bowel diseases synergistically with other therapeutic strategies.

The development of food-grade carriers based on EFSA and/or FDA-approved polymeric materials is an area of growing interest for the targeted delivery of bioactive compounds to the colon. Many nutraceuticals have shown promise in the local treatment of conditions that threaten quality of life, such as ulcerative colitis, Crohn’s disease, colorectal cancer, dysbiosis and other problems affecting the gut and colon. Nevertheless, their bioavailability is often limited due to poor solubility, rapid metabolism and low permeability, as well as undesirable local side effects. Encapsulation in carriers, which can protect the active ingredient from degradation and improve absorption and targeted administration in the colon, is one way to overcome these limitations. The technological characterization of these systems is important to assess their efficacy, safety and stability. In particular, morphology, size and surface properties influence their actions and interaction with the bio-phase. Meanwhile, encapsulation efficiency, profile and in vitro release kinetics are key parameters to assess the ability to reach the target site. This paper proposes a recent review of food-grade polymer-based systems for colorectal targeting of bioactive substances, focusing on their technological characterization and assessment of stability and biological activity, which are important in determining their full bench-to-bed potential.