Aim: Quercetin (Q1) is a flavonoid widely present in plants and endowed with several pharmacological properties mostly due to its antioxidant potential. Q1 shows anticancer activity and could be useful in cancer prevention. On the other hand, Q1 is poorly soluble in water and unstable in physiological systems, and its bioavailability is very low. Methods: A small set of Q1 derivatives (Q2–Q9) has been synthesized following opportunely modified chemical procedures previously reported. Anticancer activity has been evaluated by MTT assay. Human Topoisomerases inhibition has been performed by direct enzymatic assays. Apoptosis has been evaluated by TUNEL assay. ROS production and scavenging activity have been determined by immunofluorescence. Results: The anticancer profile of a small library of Q1 analogues, in which the OH groups were all or partially replaced with hydrophobic functional groups, has been evaluated. Two of the studied compounds demonstrated an interesting cytotoxic profile in two breast canc...

Meta-tetra(hydroxyphenyl)chlorin (mTHPC) is one of the most potent second generation photosensitizers, clinically used for photodynamic therapy (PDT) of head and neck squamous cell carcinomas. However, improvements are still required concerning its present formulation (i.e. Foscan®, a solution of mTHPC in ethanol/propylene glycol (40:60 w/w)), as mTHPC has the tendency to aggregate in aqueous media, e.g. biological fluids, and it has limited tumor specificity. In the present study, polymeric micelles with three different diameters (17, 24 and 45 nm) based on benzyl-poly(ɛ-caprolactone)-b-poly(ethylene glycol) (PCLn-PEG; n=9, 15 or 23) were prepared with mTHPC loadings ranging from 0.5 to 10 wt% using a film hydration method as advanced nanoformulations for this photosensitizer. To favor the uptake of the micelles by cancer cells that over-express the epidermal growth factor receptor (EGFR), the micelles were decorated with an EGFR targeted nanobody (named EGa1) through maleimide-thiol chemistry. The enhanced binding of the EGFR targeted micelles at 4 ℃ to EGFR over-expressing A431 cells, compared to low EGFR expressing HeLa cells, confirmed the specificity of the micelles. In addition, an enhanced uptake of mTHPC loaded micelles by A431 cells was observed when these were decorated with EGa1 nanobody, compared to non-targeted micelles. Both binding and uptake of targeted micelles were blocked by an excess of free EGa1 nanobody, demonstrating that these processes occur through EGFR. In line with this, mTHPC-loaded in EGa1-conjugated PCL23-PEG (EGa1-P23) micelles demonstrated 4 times higher photocytotoxicity on A431 cells, compared to micelles lacking the nanobody. Importantly, EGa1-P23 micelles also showed selective PDT against A431 cells compared to the low EGFR-expressing HeLa cells. Finally, an in vivo pharmacokinetic study shows that after iv injection, mTHPC incorporated in the P23 micelles displayed prolonged blood circulation kinetics, compared to free mTHPC, independently of the presence of EGa1. Thus, these results make these micelles a promising nanomedicine formulation for selective therapy.

The aim of the present work was the preparation of a magnetic hydrogel for guided release of sunitinib malate (SUM), an anticancer drug. Precipitation polymerization method has been employed in order to synthesize the hydrogel, using methacrylic acid (MAA), ethylene glycol dimethacrylate (EGDMA), glycidyl methacrylate (GMA) and 2,2′-azobisisobutyronitrile (AIBN) as monomer, cross-linker, pro-hydrophilic monomer and initiator, respectively. To confer magnetic responsiveness, particles of magnetite have been encapsulated during the polymerization process, followed by epoxide ring opening on the nanospheres' surface, in order to obtain a restricted access material (RAM) with low protein adsorption ability and improved biocompatibility. The successful introduction of magnetite has been confirmed through FT-IR and TG analyses, while protein adsorbing tests have been conducted to verify the RAM features. Furthermore, swelling properties have been evaluated before and after epoxide ring opening. Finally, in vitro tests have been performed to evaluate the release profile and cytotoxic effect on ARO, WRO, HeLa and MCF-7 cell lines.

The aim of the present study was the development of a “smart bandage” for the topical administration of diclofenac, in the treatment of localized painful and inflammatory conditions, incorporating Molecularly Imprinted Polymers (MIPs) for the controlled release of this anti-inflammatory drug. For this purpose, MIP spherical particles were synthesized by precipitation polymerization, loaded with the therapeutic agent and incorporated into the bandage surface. Batch adsorption binding studies were performed to investigate the adsorption isotherms and kinetics and the selective recognition abilities of the synthesized MIP. In vitro diffusion studies were also carried out using Franz cells and the obtained results were reported as percentage of the diffused dose, cumulative amount of diffused drug, steady-state drug flux and permeability coefficient. Moreover, the biocompatibility of the developed device was evaluated using the EPISKIN™ model. The Scatchard analysis indicated that the prepared MIP is characterized by the presence of specific binding sites for diclofenac, which are not present in the corresponding non-imprinted polymer, and the obtained results confirmed both the ability of the prepared bandage to prolong the drug release and the absence of skin irritation reactions. Therefore, these results support the potential application of the developed “smart bandage” as topical device for diclofenac sustained release.