A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth.

Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer.

Molecularly Imprinted Microrods via Mesophase Polymerization.

The aim of the present research work was the synthesis of molecularly imprinted polymers (MIPs) with a rod-like geometry via "mesophase polymerization". The ternary lyotropic system consisting of sodium dodecyl sulfate (SDS), water, and decanol was chosen to prepare a hexagonal mesophase to direct the morphology of the synthesized imprinted polymers using theophylline, methacrylic acid, and ethylene glycol dimethacrylate as a drug model template, a functional monomer, and a crosslinker, respectively. The obtained molecularly imprinted microrods (MIMs) were assessed by performing binding experiments and in vitro release studies, and the obtained results highlighted good selective recognition abilities and sustained release properties. In conclusion, the adopted synthetic strategy involving a lyotropic mesophase system allows for the preparation of effective MIPs characterized by a rod-like morphology.

Synthesis and Antitumor Activity of New Group 3 Metallocene Complexes.

The quest for alternative drugs with respect to the well-known cis-platin and its derivatives, which are still used in more than 50% of the treatment regimens for patients suffering from cancer, is highly needed. In this context, organometallic compounds, which are defined as metal complexes containing at least one direct covalent metal-carbon bond, have recently been found to be promising anticancer drug candidates. A series of new metallocene complexes with scandium, yttrium, and neodymium have been prepared and characterized. Some of these compounds show a very interesting anti-proliferative activity in triple negative breast cancer cell line (MDA.MB231) and the non-hormone sensitive prostate cancer cell line (DU145). Moreover, the interaction of some of them with biological membranes, evaluated using liposomes as bio-membrane mimetic model systems, seems to be relevant. The biological activity of these compounds, particularly those based on yttrium, already effective at low concentrations on both cancer cell lines, should be taken into account with regard to new therapeutic approaches in anticancer therapy.

N-alkyl carbazole derivatives as new tools for Alzheimer's disease: preliminary studies.

Alzheimer's disease (AD) is a progressive and age-related neurodegenerative disorder affecting brain cells and is the most common form of "dementia", because of the cognitive detriment which takes place. Neuronal disruption represents its major feature, due to the cytosolic accumulation of amyloid ß-peptide (Aß) which leads to senile plaques formation and intracellular neurofibrillary tangles. Many studies have focused on the design and therapeutic use of new molecules able to inhibit Aß aggregation. In this context, we evaluated the ability of two recently synthesized series of N-alkyl carbazole derivatives to increase the Aß soluble forms, through molecular docking simulations and in vitro experiments. Our data evidenced that two carbazole derivatives, the most active, adopt distinct binding modes involving key residues for Aß fibrillization. They exhibit a good interfering activity on Aß aggregation in mouse (N2a) cells, stably expressing wild-type human amyloid precursor protein (APP) 695. These preliminary results are promising and we are confident that the N-alkyl carbazole derivatives may encourage next future studies needed for enlarging the knowledge about the AD disease approach.

3D-Printed Alginate/Pectin-Based Patches Loaded with Olive Leaf Extracts for Wound Healing Applications: Development, Characterization and In Vitro Evaluation of Biological Properties.

Traditional wound dressings may lack suitability for diverse wound types and individual patient requirements. In this context, this study aimed to innovate wound care by developing a 3D-printed patch using alginate and pectin and incorporating Olive Leaf Extract (OLE) as an active ingredient. Different polymer-to-plasticizer ratios were systematically examined to formulate a printable ink with optimal viscosity. The resultant film, enriched with OLE, exhibited a substantial polyphenolic content of 13.15 ± 0.41 mg CAE/g, showcasing significant antioxidant and anti-inflammatory properties. Notably, the film demonstrated potent scavenging abilities against DPPH, ABTS, and NO radicals, with IC50 values of 0.66 ± 0.07, 0.47 ± 0.04, and 2.02 ± 0.14 mg/mL, respectively. In vitro release and diffusion studies were carried out and the release profiles revealed an almost complete release of polyphenols from the patch within 48 h. Additionally, the fabricated film exhibited the capacity to enhance cell motility and accelerate wound healing, evidenced by increased collagen I expression in BJ fibroblast cells. Structural assessments affirmed the ability of the patch to absorb exudates and maintain the optimal moisture balance, while biocompatibility studies underscored its suitability for biomedical applications. These compelling findings endorse the potential application of the developed film in advanced wound care, with the prospect of tailoring patches to individual patient needs.

Biological activity of 3-chloro-azetidin-2-one derivatives having interesting antiproliferative activity on human breast cancer cell lines.

Resveratrol (3,4',5 tri-hydroxystilbene), a natural plant polyphenol, has gained interest as a non-toxic agent capable of inducing tumor cell death in a variety of cancer types. However, therapeutic application of these beneficial effects remains very limited due to its short biological half-life, labile properties, rapid metabolism and elimination. Different studies were undertaken to obtain synthetic analogs of resveratrol with major bioavailability and anticancer activity. We have synthesized a series 3-chloro-azetidin-2-one derivatives, in which an azetidinone nucleus connects two aromatic rings. Aim of the present study was to investigate the effects of these new 3-chloro-azetidin-2-one resveratrol derivatives on human breast cancer cell lines proliferation. Our results indicate that some azetidin-based resveratrol derivatives may become new potent alternative tools for the treatment of human breast cancer.

Flavonoids preservation and release by methacrylic acid-grafted (N-vinyl-pyrrolidone).

CONTEXT: Flavonoids preservation and release. OBJECTIVE: Synthesis of a polymeric material able to prevent thermal and photo degradation of a flavonoid model compound, such as (+)-catechin, and suitable for a controlled/sustained delivery of this molecule in gastro-intestinal simulating fluids. MATERIALS AND METHODS: Methacrylic acid (MAA) was grafted onto poly(N-vinyl-pyrrolidone) (PVP) by a free radical grafting procedure involving a single-step reaction at room temperature. For this purpose, hydrogen peroxide/ascorbic acid redox pair was employed as water-soluble and biocompatible initiator system. RESULTS AND DISCUSSION: FT-IR spectra confirmed the insertion of MAA onto the polymeric chain. Stability studies, performed under various conditions, such as freeze-thaw cycles, exposure to strong light, thermal stability studies under constant humidity and with light protection at different temperatures, showed the preservative properties of the polymeric material towards flavonoids. Furthermore, the biocompatibility was highlighted by Hen's Egg Test-Chorioallantoic Membrane assay and in vitro release studies demonstrated the possibility to employ PVP-MAA copolymer as a device for gastro-intestinal release of flavonoids. CONCLUSION: The coupling of good preservative properties together with biocompatibility and the usefulness as carrier in controlled release make this kind of material very interesting from an industrial point of view for different applications in food, pharmaceutical, and cosmetic fields.

Polysaccharide-Based Hydrogels and Their Application as Drug Delivery Systems in Cancer Treatment: A Review.

Hydrogels are three-dimensional crosslinked structures with physicochemical properties similar to the extracellular matrix (ECM). By changing the hydrogel's material type, crosslinking, molecular weight, chemical surface, and functionalization, it is possible to mimic the mechanical properties of native tissues. Hydrogels are currently used in the biomedical and pharmaceutical fields for drug delivery systems, wound dressings, tissue engineering, and contact lenses. Lately, research has been focused on hydrogels from natural sources. Polysaccharides have drawn attention in recent years as a promising material for biological applications, due to their biocompatibility, biodegradability, non-toxicity, and excellent mechanical properties. Polysaccharide-based hydrogels can be used as drug delivery systems for the efficient release of various types of cancer therapeutics, enhancing the therapeutic efficacy and minimizing potential side effects. This review summarizes hydrogels' classification, properties, and synthesis methods. Furthermore, it also covers several important natural polysaccharides (chitosan, alginate, hyaluronic acid, cellulose, and carrageenan) widely used as hydrogels for drug delivery and, in particular, their application in cancer treatment.

Natural and Synthetic Polymeric Biomaterials for Application in Wound Management.

Biomaterials are at the forefront of the future, finding a variety of applications in the biomedical field, especially in wound healing, thanks to their biocompatible and biodegradable properties. Wounds spontaneously try to heal through a series of interconnected processes involving several initiators and mediators such as cytokines, macrophages, and fibroblasts. The combination of biopolymers with wound healing properties may provide opportunities to synthesize matrices that stimulate and trigger target cell responses crucial to the healing process. This review outlines the optimal management and care required for wound treatment with a special focus on biopolymers, drug-delivery systems, and nanotechnologies used for enhanced wound healing applications. Researchers have utilized a range of techniques to produce wound dressings, leading to products with different characteristics. Each method comes with its unique strengths and limitations, which are important to consider. The future trajectory in wound dressing advancement should prioritize economical and eco-friendly methodologies, along with improving the efficacy of constituent materials. The aim of this work is to give researchers the possibility to evaluate the proper materials for wound dressing preparation and to better understand the optimal synthesis conditions as well as the most effective bioactive molecules to load.

Dextran-catechin conjugate: a potential treatment against the pancreatic ductal adenocarcinoma.

PURPOSE: A polysaccharide-flavonoid conjugate was developend and proposed for the treatment of pancreatic ductal adenocarcinoma (PDAC). METHODS: The conjugate was synthesized by free radical grafting reaction between catechin and dextran. The chemical characterization of the conjugate was obtained by UV-Vis, 1H-NMR, FT-IR and GPC analyses, while the functionalization degree was determined by the Folin-Ciocalteu assay. The biological activity of the catechin-dextran conjugate was tested on two different cell lines derived from human pancreatic cancer (MIA PaCa-2 and PL45 cells), and the toxicity towards human pancreatic nestin-expressing cells evaluated. RESULTS: Both the cancer cell lines are killed when exposed to the conjugate, and undergo apoptosis after the incubation with catechin-dextran which resulted more effective in killing pancreatic tumor cells compared to the catechin alone. Moreover, our experimental data indicate that the conjugate was less cytotoxic to human pancreatic nestin-expressing cells which are considered a good model of non-neoplastic pancreatic cells. CONCLUSION: The suitability of newly synthesized Dextran-Catechin conjugate in the treatment of PDAC was proved confirming the high potential application of the proposed macromolecula system in the cancer therapy.

Starch-quercetin conjugate by radical grafting: synthesis and biological characterization.

A novel flavonoid-polysaccharide conjugate was synthesized by free radical grafting of quercetin on starch. The covalent insertion of quercetin in the polymeric chain was confirmed by FT-IR, DSC and fluorescence analyses, while an estimation of the amount of quercetin bound per g of polymer was obtained by the Folin-Ciocalteu assay. The conjugate shows improved UV stability and retains the antioxidant properties of free quercetin, such as scavenging activity towards free radicals (DPPH and peroxynitrite); inhibition of the free radical formation (peroxidation of linoleic acid) and total antioxidant activity. The conjugate also prevented drug degradation and shows potential health functionality in the treatment of Alzheimer disease, diabetes and as skin-whitening agent.

The Evolution of Molecular Recognition: From Antibodies to Molecularly Imprinted Polymers (MIPs) as Artificial Counterpart.

Molecular recognition is a useful property shared by various molecules, such as antibodies, aptamers and molecularly imprinted polymers (MIPs). It allows these molecules to be potentially involved in many applications including biological and pharmaceutical research, diagnostics, theranostics, therapy and drug delivery. Antibodies, naturally produced by plasma cells, have been exploited for this purpose, but they present noticeable drawbacks, above all production cost and time. Therefore, several research studies for similar applications have been carried out about MIPs and the main studies are reported in this review. MIPs, indeed, are more versatile and cost-effective than conventional antibodies, but the lack of toxicity studies and their scarce use for practical applications, make it that further investigations on this kind of molecules need to be conducted.

Synthesis and evaluation of wound healing properties of hydro-diab hydrogel loaded with green-synthetized AGNPS: in vitro and in ex vivo studies.

In diabetic patients, the presence of neuropathy, peripheral vascular diseases and ischemia, leads to the formation of foot ulcerations with a higher risk of infection because the normal response to bacterial infection is missing. In the aim to control and treat diabetic foot ulcerations (DFUs), wound dressings that are able to absorb exudate, to prevent infections, and to promote wound healing are needed. For this reason, the aim of the present research was to synthetize a biocompatible hydrogel (called HyDrO-DiAb) composed of carboxymethylcellulose loaded with silver nanoparticles (AgNPs) for the treatment of diabetic foot ulcers. In this study, AgNPs were obtained by a green synthesis and, then, were dissolved in a CMC hydrogel that, after a freeze drying process, becomes a flexible and porous structure. The in vitro and in ex vivo wound healing activity of the obtained HyDrO-DiAb hydrogel was evaluated.

Barrier effect and wound healing activity of the medical device REF-FTP78 in the treatment of gastroesophageal reflux disease.

REF-FTP78 is a class IIb medical device present on the market with different trade names and developed for the treatment of gastroesophageal reflux disease (GERD). This medical device is based on polysaccharides from Aloe Barbadensis and fucoidans from brown seaweeds, such as Undaria pinnatifida and Fucus vesiculosus, and aims to exert a protective effect on the esophageal mucosa against the noxious components of refluxate. The present study reports on the efficacy of REF-FTP78 devoting a particular attention to the barrier effect and wound healing properties, combined with antioxidant and anti-inflammatory activities. Film-forming properties and barrier effect were investigated on in vitro reconstructed human esophageal epithelium, through TEER measurement and evaluation of caffeine and Lucifer yellow permeability, and in an ex vivo swine model of esophageal mucosa damage. Antioxidant and anti-inflammatory properties were evaluated in terms of scavenging activity towards DPPH, ABTS and NO radicals and a wound healing assay was carried out to study the influence of the product on cell migration. The obtained results highlighted a significant barrier effect, with a reduction in caffeine penetration equal to 65.3%, the ability to both repair and prevent the damage caused by an acid insult, confirmed by a good transepithelial resistance for the tissue treated with the tested item, and the capacity to promote wound healing. Furthermore, the tested product showed good antioxidant and anti-inflammatory properties in the performed radical scavenging assays. These findings support the use of REF-FTP78 in the treatment of GERD.

Design and development of plastic antibodies against SARS-CoV-2 RBD based on molecularly imprinted polymers that inhibit in vitro virus infection.

The present research study reports the development of plastic antibodies based on Molecularly Imprinted Polymers (MIPs) capable of selectively binding a portion of the novel coronavirus SARS-CoV-2 spike protein. Indeed, molecular imprinting represents a very promising and attractive technology for the synthesis of MIPs characterized by specific recognition abilities for a target molecule. Given these characteristics, MIPs can be considered tailor-made synthetic antibodies obtained by a templating process. After in silico analysis, imprinted nanoparticles were synthesized by inverse microemulsion polymerization and their ability to prevent the interaction between ACE2 and the receptor-binding domain of SARS-CoV-2 was investigated. Of relevance, the developed synthetic antibodies are capable of significantly inhibiting virus replication in Vero cell culture, suggesting their potential application in the treatment, prevention and diagnosis of SARS-CoV-2 infection.

Gastro-intestinal sustained release of phytic acid by molecularly imprinted microparticles.

In this work, the possibility to employ molecularly imprinted polymers as base excipients for controlled drug delivery devices was demonstrated. As template molecule, our attention was focused on phytic acid, a water soluble antioxidant compound. The possibility to raise a controlled/sustained release of an antioxidant agent is very useful from an application point of view; in recent years, indeed, biomedical applications of antioxidants have greatly grown because the link between human diseases and oxidative stress were proved. Polymers were synthesized using methacrylic acid as functional monomer and N,N'-Ethylenebis(acrylamide) as crosslinker. After the evaluation of the imprinting efficiency of the synthesized materials by binding experiments in which the percentage of phytic acid bounded by the molecularly imprinted polymers was found to be remarkably higher compared to the non-imprinted ones, MIP were tested as a controlled release device for the antioxidant in gastrointestinal simulating fluids.

Molecularly Imprinted Polymers (MIPs) as Theranostic Systems for Sunitinib Controlled Release and Self-Monitoring in Cancer Therapy.

Cytotoxic agents that are used conventionally in cancer therapy present limitations that affect their efficacy and safety profile, leading to serious adverse effects. In the aim to overcome these drawbacks, different approaches have been investigated and, among them, theranostics is attracting interest. This new field of medicine combines diagnosis with targeted therapy; therefore, the aim of this study was the preparation and characterization of Molecularly Imprinted Polymers (MIPs) selective for the anticancer drug Sunitinib (SUT) for the development of a novel theranostic system that is able to integrate the drug controlled release ability of MIPs with Rhodamine 6G as a fluorescent marker. MIPs were synthesized by precipitation polymerization and then functionalized with Rhodamine 6G by radical grafting. The obtained polymeric particles were characterized in terms of particles size and distribution, ξ-potential and fluorescent, and hydrophilic properties. Moreover, adsorption isotherms and kinetics and in vitro release properties were also investigated. The obtained binding data confirmed the selective recognition properties of MIP, revealing that SUT adsorption better fitted the Langmuir model, while the adsorption process followed the pseudo-first order kinetic model. Finally, the in vitro release studies highlighted the SUT controlled release behavior of MIP, which was well fitted with the Ritger-Peppas kinetic model. Therefore, the synthesized fluorescent MIP represents a promising material for the development of a theranostic platform for Sunitinib controlled release and self-monitoring in cancer therapy.

Controlled Release of 5-FU from Chi-DHA Nanoparticles Synthetized with Ionic Gelation Technique: Evaluation of Release Profile Kinetics and Cytotoxicity Effect.

The ionic gelation technique allows us to obtain nanoparticles able to function as carriers for hydrophobic anticancer drugs, such as 5-fluoruracil (5-FU). In this study, reticulated chitosan- docosahexaenoic acid (Chi-DHAr) nanoparticles were synthesized by using a chemical reaction between amine groups of chitosan (Chi) and carboxylic acids of docosahexaenoic acid (DHA) and the presence of a link between Chi and DHA was confirmed by FT-IR, while the size and morphology of the obtained Chi-DHAr nanoparticles was evaluated with dynamic light scattering (DLS) and scanning electron microscopy (SEM), respectively. Drug-loading content (DLC) and drug-loading efficiency (DLE) of 5-FU in Chi-DHAr nanoparticles were 33.74 ± 0.19% and 7.9 ± 0.26%, respectively, while in the non-functionalized nanoparticles (Chir + 5FU), DLC, and DLE were in the ranges of 23.73 ± 0.14%, 5.62%, and 0.23%, respectively. The in vitro release profile, performed in phosphate buffer saline (PBS, pH 7.4) at 37 °C, indicated that the synthetized Chi-DHAr nanoparticles provided a sustained release of 5-FU. Based on the obtained regression coefficient value (R2), the first order kinetic model provided the best fit for both Chir and Chi-DHAr nanoparticles. Finally, cytotoxicity studies of chitosan, 5-FU, Chir, Chir + 5-FU, Chi-DHAr, and Chi-DHAr + 5-FU nanoparticles were conducted. Overall, Chi-DHAr nanoparticles proved to be much more biocompatible than Chir nanoparticles while retaining the ability to release the drug with high efficiency, especially towards specific types of cancerous cells.

Cardiac and Metabolic Impact of Functional Foods with Antioxidant Properties Based on Whey Derived Proteins Enriched with Hemp Seed Oil.

The impaired ability to feed properly, evident in oncologic, elderly, and dysphagic patients, may result in malnutrition and sarcopenia. Increasing the consumption of dietary proteins by functional foods and enriching their composition by adding beneficial nutrients may represent an adjuvant therapy. We aimed to evaluate the safety and the positive effects of a standard diet (SD) supplemented with whey-derived protein puddings (WDPP), with appropriate rheological properties, and hemp seed oil (HSO), rich in polyphenols. Rats were assigned to SD, WDPP, WDPP plus hemp seed oil (HSOP), and HSO supplemented diets for eight weeks. "Anthropometric", metabolic, and biochemical variables, oxidative stress, tissue injury, liver histology, and cardiac susceptibility to ischemia/reperfusion were analyzed. All the supplementations did not induce significant changes in biochemical and metabolic variables, also in relation to glucose tolerance, and livers did not undergo morphological alteration and injury. An improvement of cardiac post-ischemic function in the Langendorff perfused heart model and a reduction of infarct size were observed in WDPP and HSOP groups, thanks to their antioxidant effects and the activation of Akt- and AMPK-dependent protective pathways. Data suggest that (i) functional foods enriched with WDPP and HSOP may be used to approach malnutrition and sarcopenia successfully under disabling conditions, also conferring cardioprotection, and that (ii) adequate rheological properties could positively impact dysphagia-related problems.

Synthesis of antioxidant polymers by grafting of gallic acid and catechin on gelatin.

A novel, simple, and cheap method to synthesize antioxidant-protein conjugates by grafting reaction was developed employing a hydrogen peroxide-ascorbic acid pair as radical initiator system. Our challenge was to covalently bind molecules with tested antioxidant activity, as gallic acid (GA) and catechin (CT) to a biomacromolecule, as gelatin, extensively used in the pharmaceutical, cosmetic, and food industry. In this way, two gelatin conjugates, bearing GA and CT covalently bounded to a side chain of protein, were synthesized. Calorimetric, UV-vis, and fluorescence analyses were performed to verify the covalent bond between antioxidant molecules and gelatin, and the antioxidant activity of conjugates was compared to that of a control polymer submitted to the same reaction conditions without antioxidant molecule. The ability of synthesized materials to inhibit 2,2'-diphenyl-1-picrylhydrazyl, hydroxyl radicals, and linoneic acid peroxidation was determined and, to well characterized antioxidant properties of grafted biomacromolecules, disposable phenolic equivalents and total antioxidant activity were calculated. The conjugates showed a good antioxidant activity, confirming the efficiency of the synthetic strategy proposed in this paper. The results clearly showed that antioxidant moieties covalently bounded to a natural polymer allow to introduce in the macromolecule peculiar features for specific industrial applications.