The valorization of food wastes is a challenging opportunity for a green, sustainable, and competitive development of industry. Approximately 30 million m³ of olive mill wastewater (OMWW) are produced annually in the world as a by-product of the olive oil extraction process. In addition to being a serious environmental and economic issue because of their polluting load, OMWW can also represent a precious resource of high-added-value molecules such as polyphenols that show acclaimed antioxidant and anti-inflammatory activities and can find useful applications in the pharmaceutical industry. In particular, the possibility to develop novel nutraceutical ophthalmic formulations containing free radical scavengers would represent an important therapeutic opportunity for all inflammatory diseases of the ocular surface. In this work, different adsorbents were tested to selectively recover a fraction that is rich in polyphenols from OMWW. Afterward, cytotoxicity and antioxidant/anti-inflammatory activities of polyphenolic fraction were evaluated through in vitro tests. Our results showed that the fraction (0.01%) had no toxic effects and was able to protect cells against oxidant and inflammatory stimulus, reducing reactive oxygen species and TNF-α levels. Finally, a novel stable ophthalmic hydrogel containing a polyphenolic fraction (0.01%) was formulated and the technical and economic feasibility of the process at a pre-industrial level was investigated.

The use of iodine as antiseptic poses some issues related to its low water solubility and high volatility. Stable solid iodine-containing formulations are highly advisable and currently limited to the povidone-iodine complex. In this study, complexes of molecular iodine with 2-hydroxypropyl α-, β- and γ-cyclodextrins were considered water-soluble iodophors and prepared in a solid state by using three different methods (liquid-assisted grinding, co-evaporation and sealed heating). The obtained solids were evaluated for their iodine content and stability over time in different conditions using a fully validated UV method. The assessment of the actual formation of an inclusion complex in a solid state was carried out by thermal analysis, and the presence of iodine was further confirmed by SEM/EDX and XPS analyses. High levels of iodine content (8.3–10.8%) were obtained with all the tested cyclodextrins, and some influence was exerted by the employed preparation method. Potential use as solid iodophors can be envisaged for these iodine complexes, among which those with 2-hydroxypropyl-α-cyclodextrin were found the most stable, regardless of the preparation technique. The three prepared cyclodextrin–iodine complexes proved effective as bactericides against S. epidermidis.

This study endeavored to overcome the physiological barriers hindering optimal bioavailability in ophthalmic therapeutics by devising drug delivery platforms that allow therapeutically effective drug concentrations in ocular tissues for prolonged times. Thermosensitive drug delivery platforms were formulated by blending poloxamers (F68 and F127) with low-molecular-weight hyaluronic acid (HA) in various concentrations and loaded with hydrocortisone (HC). Among the formulations examined, only three were deemed suitable based on their desirable gelling properties at a temperature close to the eye’s surface conditions while also ensuring minimal gelation time for swift ocular application. Rheological analyses unveiled the ability of the formulations to develop gels at suitable temperatures, elucidating the gel-like characteristics around the physiological temperature essential for sustained drug release. The differential scanning calorimetry findings elucidated intricate hydrogel–water interactions, indicating that HA affects the water–polymer interactions within the gel by increasing the platform hydrophilicity. Also, in vitro drug release studies demonstrated significant hydrocortisone release within 8 h, governed by an anomalous transport mechanism, prompting further investigation for optimized release kinetics. The produced platforms offer promising prospects for efficacious ocular drug delivery, addressing pivotal challenges in ocular therapeutics and heralding future advancements in the domain.

Povidone iodine (PVPI) is an antiseptic widely used against a broad spectrum of pathogens. However, undesired side-effects are still associated with PVPI treatment due to the irritant effect of iodine. Reducing the concentration of a PVPI formulation could provide safer and more friendly formulations, for routine use and applications in very delicate organs such as the eye. However, managing the storage of a low-concentration solution of PVPI is challenging due to the high iodine volatility. In this study, we demonstrated that an amphiphilic p-sulfonato-calix[4]arene derivative forming micelles (SC4OC6) improves the stability of a 0.1% PVPI aqueous buffered solution. UV-vis and NMR spectra as well as dynamic and electrophoretic light scattering measurements showed that SC4OC6 establishes non-covalent supramolecular interactions with PVPI, resulting in the formation of nanoaggregates with a negatively charged surface. Isothermal titration calorimetry provided the aggregation parameters and evidenced that the formation of the supramolecular assembly is an enthalpically favored process. The interaction of SC4OC6 with PVPI enhances the iodine retention and stability of the solution without affecting the rapid and effective bactericidal activity of PVPI, as demonstrated by a time-killing assay with Staphylococcus epidermidis.

Iodine is a broad-spectrum antiseptic with the advantage of not inducing bacterial resistance, but its use is limited by volatility. This issue can be overcome by using "iodophors", which are molecular systems able to retain iodine and provide its sustained release. Cyclodextrins have proven effective in stabilizing iodine in solution through the formation of complexes, the preparation of which in solid form could offer additional benefits in terms of handling and storage. A series of cyclodextrins (CD) were tested for their ability to form solid complexes with iodine and it was found that the addition of potassium iodide in the solid-state preparation of the complexes significantly increases both iodine incorporation and long-term stability compared to the solids obtained without added potassium iodide. Dilute aqueous solutions of the obtained complexes were monitored for their iodine content in different conditions and excellent stability was observed in some cases. Furthermore, these cyclodextrin‑iodine complexes showed no cytotoxic effects on human corneal epithelial cells (HCE-2) while displayed very high antimicrobial (against Staphylococcus epidermis) and antiviral (against Human adenovirus 5) activities. These findings highlight the potential of cyclodextrins as a versatile platform for the development of solid iodophors as an alternative to the traditional povidone-iodide formulation.

Dr Aleo synthesised cyclodextrin-iodine complexes with diverse applications, including pharmaceuticals, agriculture, and materials science.