Breast cancer, with around 2 million new cases in 2019, is the second most common cancer worldwide and the second leading cause of cancer death among females. The aim of this work is to prepare a targeting nanoparticle through the conjugation of LinTT1 peptide, a specific molecule targeting p32 protein overexpressed by breast cancer and cancer associated cells, on liposomes' surface. This approach increases the cytotoxic effects of doxorubicin (DOX) and sorafenib (SRF) co-loaded in therapeutic liposomes on both 2D and 3D breast cancer cellular models. The liposome functionalization leads to a higher interaction with 3D breast cancer spheroids than bare ones. Moreover, interaction studies between LinTT1-functionalized liposomes and M2 primary human macrophages show an internalization of 50% of the total nanovesicles that interact with these cells, while the other 50% results only associated to cell surface. This finding suggests the possibility to use the amount of associated liposomes to enrich the hypoxic tumor area, exploiting the ability of M2 macrophages to accumulate in the central core of tumor mass. These promising results highlight the potential use of DOX and SRF co-loaded LinTT1-functionalized liposomes as nanomedicines for the treatment of breast cancer, especially in triple negative cancer cells.

Doxorubicin hydrochloride (DOX) is currently used to treat orthotropic and metastatic breast cancer. Because of its side effects, the use of DOX in cancer patients is sometimes limited; for this reason, several scientists tried designing drug delivery systems which can improve drug therapeutic efficacy and decrease its side effects. In this study, we designed, prepared, and physiochemically characterized nonionic surfactant vesicles (NSVs) which are obtained by self-assembling different combinations of hydrophilic (Tween 20) and hydrophobic (Span 20) surfactants, with cholesterol. DOX was loaded in NSVs using a passive and pH gradient remote loading procedure, which increased drug loading from ∼1 to ∼45%. NSVs were analyzed in terms of size, shape, size distribution, zeta potential, long-term stability, entrapment efficiency, and release kinetics, and nanocarriers having the best physiochemical parameters were selected for further in vitro tests. NSVs with and without DOX were stable and showed a sustained drug release up to 72 h. In vitro studies, with MCF-7 and MDA MB 468 cells, demonstrated that NSVs, containing Span 20, were better internalized in MCF-7 and MDA MB 468 cells than NSVs with Tween 20. NSVs increased the anticancer effect of DOX in MCF-7 and MDA MB 468 cells, and this effect is time and dose dependent. In vitro studies using metastatic and nonmetastatic breast cancer cells also demonstrated that NSVs, containing Span 20, had higher cytotoxicity than NSVs with Tween 20. The resulting data suggested that DOX-loaded NSVs could be a promising nanocarrier for the potential treatment of metastatic breast cancer.

Periodontal diseases are multifactorial disorders, mainly due to severe infections and inflammation which affect the tissues (i.e., gum and dental bone) that support and surround the teeth. These pathologies are characterized by bleeding gums, pain, bad breath and, in more severe forms, can lead to the detachment of gum from teeth, causing their loss. To date it is estimated that severe periodontal diseases affect around 10% of the population worldwide thus making necessary the development of effective treatments able to both reduce the infections and inflammation in injured sites and improve the regeneration of damaged tissues. In this scenario, the use of 3D scaffolds can play a pivotal role by providing an effective platform for drugs, nanosystems, growth factors, stem cells, etc., improving the effectiveness of therapies and reducing their systemic side effects. The aim of this review is to describe the recent progress in periodontal regeneration, highlighting the influence of materials’ properties used to realize three-dimensional (3D)-scaffolds, their bio-physical characteristics and their ability to provide a biocompatible platform able to embed nanosystems.

Bergamot essential oil (BEO) and Ammonium glycyrrhizinate (AG), naturally derived compounds, have remarkable anti-inflammatory properties, thus making them suitable candidates for the treatment of skin disorders. Despite this, their inadequate physicochemical properties strongly compromise their topical application. Ultradeformable nanocarriers containing both BEO and AG were used to allow their passage through the skin, thus maximizing their therapeutic activity. Physicochemical characterization studies were performed using Zetasizer Nano ZS and Turbiscan Lab^®. The dialysis method was used to investigate the release profile of the active compounds. In vivo studies were performed on human healthy volunteers through the X-Rite spectrophotometer. The nanosystems showed suitable features for topical cutaneous administration in terms of mean size, surface charge, size distribution, and long-term stability/storability. The co-delivery of BEO and AG in the deformable systems improved both the release profile kinetic of ammonium glycyrrhizinate and deformability properties of the resulting nanosystems. The topical cutaneous administration on human volunteers confirmed the efficacy of the nanosystems. In detail, BEO and AG-co-loaded ultradeformable vesicles showed a superior activity compared to that recorded from the ones containing AG as a single agent. These results are promising and strongly encourage a potential topical application of AG/BEO co-loaded nanocarriers for anti-inflammatory therapies.

Idebenone (IDE) is a powerful antioxidant that is potentially active towards cerebral diseases, but its low water solubility and fast first pass metabolism reduce its accumulation in the brain, making it ineffective. In this work, we developed cyclodextrin-based chitosan nanospheres (CS NPs) as potential carriers for nose-to-brain targeting of IDE. Sulfobutylether-β-cyclodextrin (SBE-β-CD) was used as a polyanion for chitosan (CS) and as a complexing agent for IDE, permitting its encapsulation into nanospheres (NPs) produced in an aqueous solution. Overloading NPs were obtained by adding the soluble IDE/hydroxypropyl-β-CD (IDE/HP-β-CD) inclusion complex into the CS or SBE-β-CD solutions. We obtained homogeneous CS NPs with a hydrodynamic radius of about 140 nm, positive zeta potential (about +28 mV), and good encapsulation efficiency and drug loading, particularly for overloaded NPs. A biphasic release of IDE, finished within 48 h, was observed from overloaded NPs, whilst non-overloaded CS NPs produced a prolonged release, without a burst effect. In vitro biological studies showed the ability of CS NPs to preserve the antioxidant activity of IDE on U373 culture cells. Furthermore, Fourier transform infrared spectroscopy (FT-IR) demonstrated the ability of CS NPs to interact with the excised bovine nasal mucosa, improving the permeation of the drug and potentially favoring its accumulation in the brain.