Nanoemulsions are pivotal carriers which are increasingly adopted as carriers for poorly soluble active molecules. This review provides a critical overview of 'green' nanoemulsions, which are systems based on renewable, biodegradable, and non-toxic components and/or using sustainable production techniques. We here focus on the role of food-grade oils (including poly-unsaturated fatty acid-rich sources) and green excipients, with special attention on the interfacial properties of biosurfactants such as proteins, polysaccharides, and small-molecule surfactants. This review provides a critical overview of the formulation principles, interfacial phenomena, and physicochemical stability of green nanoemulsions, with reference to topical and pharmaceutical applications. The performance of nanoemulsions as delivery systems for bioactive lipids, essential oils, vitamins, carotenoids, phenolic compounds, and conventional drugs is examined through representative case studies. Known limitations, including oxidative instability, compositional variability, and difficulties in large scale production, are analyzed along with future opportunities in multifunctional formulations and sustainable processing. Overall, green nanoemulsions emerge as promising next-generation platforms for safe, effective, and environmentally friendly drug delivery.

This study investigates the role of hyaluronic acid (HA) in modulating the structure-property relationships of an injectable composite drug delivery system (c-DDS) for ocular drug administration. The c-DDS was designed to behave as a viscous fluid at room temperature, enabling intravitreal injection, and to undergo in situ gelation at physiological ocular temperature. The system consists of a thermosensitive poloxamer-based hydrogel embedding biodegradable poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs). HA was incorporated within the hydrogel and as a surface coating on PLGA NPs to modulate the physicochemical properties of the system and control NP mobility. The hydrogels maintained their rheological properties up to four weeks, also following intravitreal injection through a fine-gauge needle and autoclave sterilization. Swelling and thermal analyses highlighted the contribution of each component to the overall behaviour of the system. Multiple particle tracking (MPT) analysis of NP diffusion within the hydrogels demonstrated a crucial role of HA in tuning NP mobility. In vitro studies using ARPE-19 cells confirmed the biocompatibility of the c-DDS and showed effective NPs internalization. Overall, this preliminary study lays a formulation framework for HA-modulated injectable composite hydrogels. This also upholds their further development as ocular delivery platforms for the loading of diverse therapeutic agents, ranging from hydrophilic to lipophilic and from low- to high-molecular weight, along with the subsequent evaluation of their biological implications.

Chronic wounds are marked by an extended healing period during which damaged tissues fail to undergo orderly and timely repair. Examples of chronic wounds encompass venous ulcers, pressure ulcers, and diabetic foot ulcers. The process of wound healing is complex and dynamic, relying on the interplay and response among various cells and mediators. In this study, four marketed wound dressing products based on cotton gauzes impregnated with different semisolid products (namely Betadine® 10%, Connettivina® Bio Plus Fitostimoline® Plus, and Non-Ad® gauzes) have been characterized for their physicochemical properties and ex vivo behaviors. More in detail, the pH and rheological features of semisolid formulations impregnating the gauzes were analyzed along with their ability to adhere to the gauzes. The most promising ones were selected and compared in ex vivo experiments on fresh pig skin. The pH measurements showed an acidic environment for all the tested solutions, albeit with variations in mean values, ranging from 2.66 to 4.50. The outcomes of rheological studies demonstrated that all the semisolid preparations impregnating the gauzes exhibited a pseudoplastic behavior, with significant differences in the pseudoplasticity index across the preparations, which is likely to influence their ability to adhere to the gauze. A rheological study in oscillatory mode revealed rheological behavior typical of a viscous solution only for the cream impregnating non-paraffin gauzes. The other products exhibited rheological behavior typical of a weak gel, which is expected to be advantageous as regards the capability of the semisolid preparation to create and maintain the space within the wound and to provide protection to the injured tissue. Results of ex vivo experiments demonstrated that Fitostimoline® Plus was more effective than Connettivina® Bio Plus in promoting both skin hydration and energy.

Natural resources, along with critical raw materials, are increasingly considered a focus for technological applications. Widely available and inexpensive natural resources, such as zeolite-rich geomaterials, possess minero-chemical characteristics that make them very useful in various technological applications, representing a strategic choice with a strong green connotation. In this research, the possibility of recycling waste powders from quarrying operations of zeolite-rich tuffs in technological applications for the construction sector and drug delivery was investigated.Waste powders collected from quarries operating on the Sorano Formation (Tuscany - Italy), were used for a preliminary characterization, performed to evaluate zeolite content and potential pollution deriving from industrial processing.Thereafter, the specific technological characterization was carried out to define the waste attitude to represent a promising candidate raw material for Lightweight Expanded Aggregates (LEA) production, partial substitution component with pozzolanic activity in cement formulations, carrier for active pharmaceutical molecules.Experimental results, obtained following European normative, proved that was possible to produce waste-based LEA with comparable features with those reported for currently marketed products, that waste powders exhibited pozzolanic activity evidencing the possible use as addition for blended cements and, finally, the use of a cationic surfactant determined a surface-modification of natural zeolites (contained in waste samples) which encouraged for an early loading trial of active pharmaceutical molecules.This research can be safely extended to other quarry waste, with similar mineralogical and chemical composition, leading to a strong contribution in the waste management of this sector.

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.

Despite its potential against several carcinomas, the pharmacological efficacy of silibinin (SLB) is hampered by poor solubility, absorption, and oral bioavailability. To face these issues, we developed polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) coated with hydrophilic polyethene oxide (PEO) for controlled and targeted SLB delivery. NPs were produced at two different SLB loadings and presented a spherical shape with smooth surfaces and stable size in water and cell culture medium. The encapsulation efficiencies were found to be >84%, and thermal analysis revealed that the SLB was present in an amorphous state within the NPs. In vitro SLB release experiments revealed that at the lowest SLB loading, desorption of the active molecule from the surface or nanoporosities of the NPs mainly dictates release. In contrast, at the highest SLB loading, diffusion primarily regulates release, with negligible contributions from other mechanisms. Cell experiments showed that, compared with the free drug, SLB loaded in the produced NPs significantly increased the bioactivity against H1299, H1975, and H358 cells.

Background:Circulating Tumor Cells (CTCs) represent a small, heterogeneous population that comprise the minority of cells able to develop metastasis. To trap and characterize CTCs with metastatic attitude, a CXCL12-loaded hyaluronic-gel (CLG) was developed. CXCR4+cells with invasive capability would infiltrate CLG. Methods:Human colon, renal, lung and ovarian cancer cells (HT29, A498, H460 and OVCAR8 respectively) were seeded on 150 μl Empty Gels (EG) or 300 ng/ml CXCL12 loaded gel (CLG) and allowed to infiltrate for 16 h. Gels were then digested and fixed with 2 % FA-HAse for human cancer cell enumeration or digested with HAse and cancer cells recovered. CLG-recovered cells migrated toward CXCL12 and were tested for colonies/spheres formation. Moreover, CXCR4, E-Cadherin and Vimentin expression was assessed through flow cytometry and RT-PCR. The clinical trial "TRAP4MET" recruited 48 metastatic/advanced cancer patients (8 OC, 8 LC, 8 GBM, 8 EC, 8 RCC and 8 EC). 10 cc whole blood were devoted to PBMCs extraction (7 cc) and ScreenCell™ filters (3 cc) CTCs evaluation. Ficoll-isolated patient's PBMCs were seeded over CLG and allowed to infiltrate for 16 h; gels were digested and fixed with 2 % FA-HAse, cells stained and DAPI+/CD45-/pan-CK + cells enumerated as CTCs. Results:Human cancer cells infiltrate CLG more efficiently than EG (CLG/EG ratio 1.25 for HT29/1.58 for A498/1.71 for H460 and 2.83 for OVCAR8). CLG-recovered HT29 cells display hybrid-mesenchymal features [low E-cadherin (40 %) and high vimentin (235 %) as compared to HT29], CXCR4 two-fold higher than HT29, efficiently migrate toward CXCL12 (two-fold higher than HT29) and developed higher number of colonies (171 ± 21 for HT29-CLG vs 131 ± 8 colonies for HT29)/larger spheres (spheroid area: 26561 ± 6142 μm2 for HT29-CLG vs 20297 ± 7238 for HT29). In TRAP4MET clinical trial, CLG-CTCs were isolated in 8/8 patients with OC, 6/8 with LC, 6/8 with CRC, 8/8 with EC, 8/8 with RCC cancer and 5/8 with GBM. Interestingly, in OC, LC and GBM, CLG isolated higher number of CTCs as compared to the conventional ScreenCell™ (CLG/SC ratio = 1.88 for OC, 2.47 for LC and 11.89 for GBM). Bland and Altman blot analysis and Passing and Bablok regression analysis showed concordance between the methodological approaches but indicate that SC and CLG are not superimposable suggesting that the two systems select cells with different features. Conclusion:CLG might represent a new and easy tool to isolate invasive CTCs in multiple cancers such as OC, LC and GBM at today orphan of reliable methods to consistently detect CTCs.

This study aimed to examine the impact of different surface properties of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (P NPs) and PLGA-Poloxamer nanoparticles (PP NPs) on their in vivo biodistribution. For this purpose, NPs were formulated via nanoprecipitation and loaded with diphenylhexatriene (DPH), a fluorescent dye. The obtained NPs underwent comprehensive characterization, encompassing their morphology, technological attributes, DPH release rate, and thermodynamic properties. The produced NPs were then administered to wild-type mice via intraperitoneal injection, and, at scheduled time intervals, the animals were euthanized. Blood samples, as well as the liver, lungs, and kidneys, were extracted for histological examination and biodistribution analysis. The findings of this investigation revealed that the presence of poloxamers led to smaller NP sizes and induced partial crystallinity in the NPs. The biodistribution and histological results from in vivo experiments evidenced that both, P and PP NPs, exhibited comparable concentrations in the bloodstream, while P NPs could not be detected in the other organs examined. Conversely, PP NPs were primarily sequestered by the lungs and, to a lesser extent, by the kidneys. Future research endeavors will focus on investigating the behavior of drug-loaded NPs in pathological animal models.

Chemical and enzymatic in vivo degradation of antimicrobial peptides represents a major challenge for their therapeutic use to treat bacterial infections. In this work, anionic polysaccharides were investigated for their ability to increase the chemical stability and achieve sustained release of such peptides. The investigated for-mulations comprised a combination of antimicrobial peptides (vancomycin (VAN) and daptomycin (DAP)) and anionic polysaccharides (xanthan gum (XA), hyaluronic acid (HA), propylene glycol alginate (PGA) and alginic acid (ALG)). VAN dissolved in buffer of pH 7.4 and incubated at 37 degrees C showed first order degradation kinetics with a reaction rate constant k(obs) of 5.5 x 10(-2) day(-1) corresponding with a half-life of 13.9 days. However, once VAN was present in a XA, HA or PGA-based hydrogel, kobs decreased to (2.1-2.3) x 10(-2) day(-1) while kobs was not affected in an alginate hydrogel and a dextran solution (5.4 x 10(-2) and 4.4 x 10(-2) day(-1)). Under the same conditions, XA and PGA also effectively decreased kobs for DAP (5.6 x 10(-2) day(-1)), whereas ALG had no effect and HA even increased the degradation rate. These results demonstrate that the investigated polysaccharides (except ALG for both peptides and HA for DAP) slowed down the degradation of VAN and DAP. DSC analysis was used to investigate on polysaccharide ability to bind water molecules. Rheological analysis highlighted that the polysaccharides containing VAN displayed an increase in G' of their formulations, pointing that the peptides interaction act as crosslinker of the polymer chains. The obtained results suggest that the mechanism of stabi-lization of VAN and DAP against hydrolytic degradation is conferred by electrostatic interactions between the ionizable amine groups of the drugs and the anionic carboxylate groups of the polysaccharides. This, in turn, results in a close proximity of the drugs to the polysaccharide chain, where the water molecules have a lower mobility and, therefore, a lower thermodynamic activity.

The widespread use of synthetic plastics, as well as the waste produced at the end of their life cycle, poses serious environmental issues. In this context, bio-based plastics, i.e., natural polymers produced from renewable resources, represent a promising alternative to petroleum-based materials. One potential source of biopolymers is waste from the food industry, the use of which also provides a sustainable and eco-friendly solution to waste management. Thus, the aim of this work concerns the extraction of polysaccharide fractions from lemon, tomato and fennel waste. Characterizing the chemical–physical and thermodynamic properties of these polysaccharides is an essential step in evaluating their potential applications. Hence, the solubility of the extracted polysaccharides in different solvents, including water and organic solvents, was determined since it is an important parameter that determines their properties and applications. Also, acid-base titration was carried out, along with thermoanalytical tests through differential scanning calorimetry. Finally, the electrospinning of waste polysaccharides was investigated to explore the feasibility of obtaining polysaccharide-based membranes. Indeed, electrospun fibers are a promising structure/system via which it is possible to apply waste polysaccharides in packaging or well-being applications. Thanks to processing feasibility, it is possible to electrospin waste polysaccharides by combining them with different materials to obtain porous 3D membranes made of nanosized fibers.

Hydrocortisone (HC) is widely utilized in the pharmaceutical field for various administration routes, including oral, parenteral, and topical routes. However, its application in ocular disease treatment as a solution is limited due to its poor aqueous solubility. To address this limitation, in this study we aimed to investigate different types of cyclodextrins (CDs) to identify the most effective CD for improving the inherent solubility of HC. Results from scanning electron microscopy, rheology and differential scanning calorimetry (DSC) demonstrated the formation of inclusion complexes, while isothermal titration calorimetry (ITC) investigations accurately determined the thermodynamic parameters associated with the formation of complexes between HC and HP beta CD or beta CD, at 25 and 37(degrees)C. Additionally, phase solubility studies in PBS buffer at 37(degrees)C confirmed the formation of stable inclusion complexes. Collectively, results indicated that HP beta CD was the most effective CD in enhancing the intrinsic solubility of HCs in PBS highlighting its potential for improving the solubility and formulation of HCbased pharmaceutical products.

Nanoparticles (NPs) coated with hyaluronic acid (HA) seem to be increasingly promising for targeted therapy due to HA chemical versatility, which allows them to bind drugs of different natures, and their affinity with the transmembrane receptor CD-44, overexpressed in tumor cells. However, an essential aspect for clinical use of NPs is formulation stability over time. For these reasons, analytical techniques capable of characterizing their physico-chemical properties are needed. In this work, poly(lactide-co-glycolide) (PLGA) NPs with an average diameter of 100-150 nm, coated with a few 10 s of nm of HA, were synthesized. For stability characterization, two complementary investigative techniques were used: Dynamic Light Scattering (DLS) and Surface-Enhanced Raman Scattering (SERS) spectroscopy. The first technique provided information on size, polidispersity index, and zeta-potential, and the second provided a deeper insight on the NP surface chemicals, allowing distinguishing of HA-coated NPs from uncoated ones. Furthermore, in order to estimate formulation stability over time, NPs were measured and monitored for two weeks. SERS results showed a progressive decrease in the signal associated with HA, which, however, is not detectable by the DLS measurements.

The treatment of posterior eye segment diseases throughintravitrealinjection requires repeated injections of an active molecule, whichmay be associated with serious side effects and poor patient compliance.One brilliant strategy to overcome these issues is the use of drug-loadedmicroparticles for sustained release, aiming at reducing the frequencyof injections. Therefore, the aim of this work was to assess the safetyfeatures of poly(lactic-co-glycolic acid) (PLGA)-based, hyaluronicacid-decorated microparticles loaded with palmitoylethanolamide (PEA),citicoline (CIT), or glial-cell-derived neurotrophic factor (GDNF).Microparticles were prepared by double emulsion-solvent evaporationand fully characterized for their technological features. Microparticlespossessed a satisfactory safety profile in vitro onhuman retinal pigment epithelial (ARPE-19) cells. Interestingly, theadministration of free GDNF led to a loss of cell viability, whileGDNF sustained release displayed a positive effect in that regard. In vivo results confirmed the safety profile of both emptyand loaded microparticles. Overall, the outcomes suggest that theproduced microparticles are promising for improving the local administrationof neuroprotective molecules. Further studies will be devoted to assessthe therapeutic ability of microparticles.

Polymeric microparticles (MPs) designed for the intravitreal administration of therapeutic proteins result in a prolonged half-life in the vitreous and can delay or discourage the onset of adverse effects inevitably related to this route of administration. Hence, here we designed MPs composed of a polymeric blend based on poly(lactic-co-glycolic) acid and poloxamers, externally decorated with hyaluronic acid. The MPs are intended for intravitreal administration of bovine serum albumin. In detail, a systematic formulative study aiming to shed light on the complex relationship between protein release rate and MP degradation rate was carried out by means of calorimetric and gel permeation chromatography analyses. We found out that poloxamer addition caused a compact MP matrix, which led to a slight modification of the degradation kinetics and a reduction in the initial BSA initial release, which is of the utmost importance to ensure a relatively regular BSA release. It must also be underlined that for acid-labile molecules such as proteins, the poloxamer's presence induced complex and hardly predictable effects on MP degradation/protein release, due to the dynamic balance between the time-evolving hydrophilicity of MPs and the influence of poloxamers themselves on the PLGA degradation rate.

Here we aimed to correlate different molecular weights of hyaluronic acid (HA), 200, 800 and 1437 kDa, used to decorate poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs), to their cell uptakes. NP internalization kinetics in CD44-overexpressing breast carcinoma cells were quantified, using healthy fibroblast cells as reference. Actually, NP uptake and selectivity by tumor cells were maximized for NPs HA 800 kDa, while being minimum for NPs HA1400 kDa. This unexpected result could be explained considering that the interaction between NPs and tumor cells is dictated by rearrangement and conformation of that segment of HA chain that actually protrudes from the NPs. Overall, results obtained in this work point at how HA molecular weight, is pivotal project parameter in NP formulation to promote active targeting in the CD44 overexpressing cancer cells.

Transcription factors (TFs) have a remarkable role in the homeostasis of the organisms and there is a growing interest in how they recognize and interact with specific DNA sequences. TFs recognize DNA using a variety of structural motifs. Among those, the ribbon-helix-helix (RHH) proteins, exemplified by the MetJ and ARC repressors, form dimers that insert antiparallel β-sheets into the major groove of DNA. A great chemical challenge consists of using the principles of DNA recognition by TFs to design minimized peptides that maintain the DNA affinity and specificity characteristics of the natural counterparts. In this context, a peptide mimic of an antiparallel β-sheet is very attractive since it can be obtained by a single peptide chain folding in a β-hairpin structure and can be as short as 14 amino acids or less. Herein, we designed eight linear and two cyclic dodeca-peptides endowed with β-hairpins. Their DNA binding properties have been investigated using fluorescence spectroscopy together with the conformational analysis through circular dichroism and solution NMR. We found that one of our peptides, peptide 6, is able to bind DNA, albeit without sequence selectivity. Notably, it shows a topological selectivity for the major groove of the DNA which is the interaction site of ARC and many other DNA-binding proteins. Moreover, we found that a type I' β-hairpin folding pattern is a favorite peptide structure for interaction with the B-DNA major groove. Peptide 6 is a valuable lead compound for the development of novel analogs with sequence selectivity.

The biomedical applications of physically entangled polymeric hydrogels are generally limited due to their weak mechanical properties, rapid swelling and dissolution in physiologically relevant environment. Chemical crosslinking helps stabilizing hydrogel structure and enhancing mechanical properties, thereby allowing a higher stability in phisiological environment. In this context, it is known that the mechanical properties of the hydrogel are affected by both the molecular weight (MW) of the starting polymer and the concentration of the crosslinker. Here, our aim was to assess the influence of polymer MW and concentration in the precursor solution on the mechanical features of the final hydrogel and their influence on cells-material interaction. In detail, 3D synthetic matrices based on poly(ethylene glycol) diacrylate (PEGDA) at two molecular weights (PEG 700 and PEG 3400) and at three different concentrations (10, 20, 40 w/v %), which were photopolymerized using darocour as an initiator, were studied. Then, infrared and swelling analyses, along with a comprehensive mechanical characterization of the obtained hydrogels (i.e. oscillatory shear and confined compression tests), were performed. Finally, to evaluate the influence of the mechanical features on the biological behaviour, the hydrogels were characterized in terms of cell adhesion percentage and cell viability after functionalizing the substrates with RGD peptide at three different concentrations. Results have demonstrated that both the Young's modulus (E) in compression and the elastic modulus (G') in shear of the hydrogels increase with increasing polymer precursor concentration. E decreased as MW increased, and the differences are more relevant for more concentrated hydrogels. On the contrary, G' appears to increase with increasing PEGDA MW and in particular for the lowest polymer precursor concentration. The biological results have demonstrated that cells cultured for longer times seem to prefer PEG 3400 hydrogels with a larger mesh size structure that posses higher viscoelastic properties in shear.

The purpose of this study was to produce poly(DL-lactic-co-glycolic acid) (PLGA) - based microparticles (MPs), externally decorated with hyaluronic acid (HA). The MPs are intended for intravitreal injections in the treatment of posterior eye segment and have been designed to prolong the release of growth factors into the vitreous body, therefore aiming to increase the time interval between two consecutive injections. The MPs, prepared by a modified double emulsion-solvent evaporation technique and loaded with bovine serum albumins (BSA) and ciliary neurotrophic factor (CNTF), were spherical, with a diameter around 70 μm and a >90% encapsulation efficiency. Energy Dispersive Spectroscopy (EDS) outcomes indicated that HA presence in the external aqueous phase of the emulsion did affect the surface properties of MPs. Moreover, poloxamers drastically slowed down MP degradation properties which are, in turn, closely related to their ability to prolong drug release. This is promising for the envisaged application of the produced MPs. Further work will be devoted to optimizing MP formulation with respect to the envisaged intravitreal route of administration.

Quercetin (QCT) is a flavonoid possessing many activities, such as neuro-/cardioprotective, anti-inflammatory and anticancer, but its pharmacological application is severely curtailed by its low water solubility and in vivo bioavailability. The formation of a QCT–hydroxypropyl-β-cyclodextrin (HPβCD) host–guest complex is promising to improve QCT therapeutic potential. Therefore, here the heat effects of HPβCD solutions with QCT solutions in water–ethanol solvents at different concentrations were studied by calorimetric titration, and the stability of molecular complexes was assessed by UV–Vis spectrophotometry. Calorimetric titrations revealed the formation of a QCT/HPβCD host–guest complex with a stoichiometric ratio of 1:1 in X(EtOH) = 0.00, 0.05 and 0.10 molar fractions of solvents at pH = 7.0 and pH = 8.1. Thermodynamic parameters of the complex formation reaction (lgK; ΔrH; TΔrS) were obtained in these experimental conditions. Differently, no complex formation was noticed in water–ethanol mixed solvent when ethanol volume fraction exceeded 0.2 at neutral and alkaline pH, as well as a volume fraction higher than 0.1 at acidic pH. Furthermore, the results of differential scanning calorimetry tests run on dried HPβCD after dissolution in hydroalcoholic solutions indicated that ethanol and water compete for the complexation within the hydrophobic cavity of HPβCD. This explains the decreased QCT complexation efficacy in the presence of ethanol beyond 0.1 or 0.2 volume fraction.

Development of distant metastasis relies on interactions between cancer and stromal cells. CXCL12, also known as stromal-derived factor 1α (SDF-1α), is a major chemokine constitutively secreted in bone marrow, lymph nodes, liver and lung, playing a critical role in the migration and seeding of neoplastic cells. CXCL12 activates the CXCR4 receptor that is overexpressed in several human cancer cells. Recent evidence reveals that tumors induce pre-metastatic niches in target organ producing tumor-derived factors. Pre-metastatic niches represent a tumor growth-favoring microenvironment in absence of cancer cells. A commercially available dermal filler, hyaluronic acid (HA) -based gel, loaded with CXCL12 (CLG) reproduced a “fake” pre-metastatic niche. In vitro, B16-hCXCR4-GFP, human cxcr4 expressing murine melanoma cells efficiently migrated toward CLG. In vivo, CLGs and empty gels (EGs) were subcutaneously injected into C57BL/6 mice and 5 days later B16-hCXCR4-GFP cells were intravenously inoculated. CLGs were able to recruit a significantly higher number of B16-hCXCR4-GFP cells as compared to EGs, with reduced lung metastasis in mice carrying CLG. CLG were infiltrated by higher number of CD45-positive leukocytes, mainly neutrophils CD11b+Ly6G+ cells, myeloid CD11b+Ly6G- and macrophages F4/80. CLG recovered cells recapitulated the features of B16-hCXCR4-GFP (epithelial, melanin rich, MELAN A/ S100/ c-Kit/CXCR4 pos; α-SMA neg). Thus a HA-based dermal filler loaded with CXCL12 can attract and trap CXCR4+tumor cells. The CLG trapped cells can be recovered and biologically characterized. As a corollary, a reduction in CXCR4 dependent lung metastasis was detected.