Nanogel-antimiR-31 conjugates affect colon cancer cells behaviour

Soft and flexible nanogels, produced by electron beam (e-beam) irradiation of poly(N-vinyl pyrrolidone) and acrylic acid, were evaluated as delivery devices of the inhibitor of miR-31, a small RNA molecule with an important role in colorectal cancer (CRC) progression. The nanogel carriers developed possess both carboxyl and primary amino groups; the former were activated to react with the primary amino group present in the purposely-functionalised AntimiR-31. Very high conjugation reaction yields were attained, as well as a remarkable colloidal and storage stability of the conjugates. The ability of these nanoconstructs to be internalized by cells and the specific interaction of conjugated …

Nose-to-brain delivery of insulin enhanced by radiation-engineered nanogels

Recent evidences suggest thet insulin delivery to the brain can be an important pharmacological therapy for some neurodegenerative pathologies, including Alzheimer disease (AD)

On the mechanism of radiation synthesis of nanogels

Radiation-engineered poly(N-vinyl pyrrolidone) nanogels are very interesting biocompatible nanocarriers for i.v. administration of therapeutics and contrast agents for bioimaging among other applications. Nanogels are usually produced upon irradiation of dilute aqueous polymer solutions. Under these conditions, the polymer radicals formed primarily react via intramolecular radical-radical combination forming intramolecular crosslinks. The manufacturing process is fast and effective and grants excellent control of particle size and simultaneous sterilization of the formed nanogels. Interestingly, primary amino groups and carboxyl groups, useful for (bio)conjugation, are also formed in a dose…

Radiation synthesis of nanogels as therapeutic agent vectors

Nanogels (NGs) are physically or chemically crosslinked polymer networks and are promising candidates in the development of therapeutic agent vectors. In fact, thanks to their tunable size and properties, they offer unique advantages, including a large and flexible surface for multivalent bio-conjugation, an internal 3D aqueous environment for incorporation and protection of (bio)molecular drugs, stimuliresponsiveness to achieve temporal and/or site control of the release function and biocompatibility. In order to develop effective NGs-based biomedical devices an inexpensive, robust and versatile synthetic methodology is required. In this perspective, we have produced NGs with high yields a…

Numerical simulations of the kinetics of pulsed electron beam induced synthesis of nanogels in dilute aqueous polymer solutions

Nanogel can be produced by irradiation of dilute aqueous polymer solutions. The nanogels are formed primarily through intramolecular radical-radical crosslinking reactions between two polymer radical sites.

Agarose/κ-carrageenan-based hydrogel film enriched with natural plant extracts for the treatment of cutaneous wounds.

Abstract Hydrogels for complex and chronic wound dressings must be conformable, absorb and retain wound exudates and maintain hydration. They can incorporate and release bioactive molecules that can accelerate the healing process. Wound dressings have to be in contact with the wound and epidermis, even for long periods, without causing adverse effects. Hydrogel dressing formulations based on biopolymers derived from terrestrial or marine flora can be relatively inexpensive and well tolerated. In the present article hydrogel films composed by agarose (1.0 wt%), κ-carrageenan at three different concentrations (0.5, 1.0 and 1.5 wt%) and glycerol (3.0 wt%) were prepared without recourse to cros…

Conjugation strategies of insulin to nanogels: new hope for nanogels Alzheimer's disease therapy?

Xyloglucan-based hydrogel film for wound dressing: Structure and biological properties relationships

Crosslinked xyloglucan-poly(vinyl alcohol) based hydrogel films have been synthetized and characterized for wound healing applications. Polyvinyl alcohol (PVA) and glycerol (Gro) were added to have an optimal combination of softness, conformability and resilience. Physical hydrogel have been transformed into permanent covalent hydrogels by reaction with glutaraldehyde (GA). Chemical and physical properties of the films have been analyzed by different technique. Moreover, biocompatibility of a selected formulation was assessed in vitro by investigating different aspects, such as cell viability, oxidative stress, mitochondrial dysfunction and specific stress biomarkers. Partial adhesiveness w…

Insulin Nanogels: a New Strategy for the Treatment of Alzheimer’s Disease

A growing body of evidence shows that Insulin, Insulin Receptor (IR) and IR signaling are involved in brain cognitive functions and their dysfunction is implicated in Alzheimer’s disease (AD) degeneration. Thus, administration of insulin could be a strategy for AD treatment. For this aim we have designed, synthesized and characterized a nanogel system (NG) to deliver insulin to the brain, as a tool for the development of a new therapy for AD. A carboxyl-functionalized poly(N-vinyl pyrrolidone) nanogel system produced by ionizing radiation was chosen as substrate for the covalent attachment of insulin or fluorescent molecules relevant for its characterization. Biocompatibility of the naked c…

Nose-to-brain delivery of insulin enhanced by a nanogel carrier.

Recent evidences suggest that insulin delivery to the brain can be an important pharmacological therapy for some neurodegenerative pathologies, including Alzheimer disease (AD). Due to the presence of the Blood Brain Barrier, a suitable carrier and an appropriate route of administration are required to increase the efficacy and safety of the treatment. Here, poly(N-vinyl pyrrolidone)-based nanogels (NG), synthetized by e-beam irradiation, alone and with covalently attached insulin (NG-In) were characterized for biocompatibility and brain delivery features in a mouse model. Preliminarily, the biodistribution of the "empty" nanocarrier after intraperitoneal (i.p.) injection was investigated b…

The role of molecular oxygen in the formation of radiation-engineered multifunctional nanogels

Abstract Nanogels are very promising biomedical nanodevices. The classic “radiation chemistry-based” approach to synthetize nanogels consists in the irradiation with pulsed electron beams of dilute, N2O-saturated, aqueous solutions of water-soluble polymers of the “crosslinking type”. Nanogels with controlled size and properties are produced in a single irradiation step with no recourse to initiators, organic solvents and surfactants. This paper combines experimental syntheses, performed with two e-beam irradiation setups and dose-ranges, starting from poly(N-vinyl pyrrolidone) solutions of various concentrations, both in N2O-saturated and air-saturated initial conditions, with the numerica…

Multifunctional nanogels from e-beam irradiation of PVP aqueous solutions, only

Nanogels (NGs) are 3D networks of crosslinked hydrophilic polymers with nanoscalar dimensions. Due to their structure and physico-chemical properties, they are a promising nanomaterial platform for site-specific drug delivery and diagnostic nanodevices.

NANOGELS AS USEFUL TOOL FOR ALZHEIMER’S DISEASE THERAPY

CONJUGATION STRATEGIES OF INSULIN TO NANOGELS AND BIOLOGICAL ACTIVITY TESTS

Ionizing radiation-engineered nanogels as insulin nanocarriers for the development of a new strategy for the treatment of Alzheimer's disease

A growing body of evidence shows the protective role of insulin in Alzheimer's disease (AD). A nanogel system (NG) to deliver insulin to the brain, as a tool for the development of a new therapy for Alzheimer's Disease (AD), is designed and synthetized. A carboxyl-functionalized poly(N-vinyl pyrrolidone) nanogel system produced by ionizing radiation is chosen as substrate for the covalent attachment of insulin or fluorescent molecules relevant for its characterization. Biocompatibility and hemocompatibility of the naked carrier is demonstrated. The insulin conjugated to the NG (NG-In) is protected by protease degradation and able to bind to insulin receptor (IR), as demonstrated by immunofl…

Radiation engineered polymer nanocarriers for a new generation of nanoparticles based tumor specific radiopharmaceuticals

High energy radiation processing for the synthesis of insulin nanocarriers for the development of a new strategy for the treatment of Alzheimer's Disease

Nanogels are nanoscalar polymeric networks, characterized by a dynamic internal structure and a flexible adaptive shape. When they are used as drug carriers, their flexibility and shape changing ability can facilitate the bypass of biological barriers, ensure protection of the payload and enable interaction of any attached ligand with its receptors. Poly(N-vinyl pyrrolidone)-co-acrylic acid nanogels (NGs) have been produced by ebeam irradiation of diluted aqueous solutions of a water-soluble polymer in the presence of a small amount of acrylic acid. In particular, industrial accelerators and the typical set-ups and doses applied for sterilization have been used. [1, 2] Particle size, molecu…

Neuroprotective effect of a new Insulin-Nanogel system

Nanogels (NGs) have a great potential in the development of “smart” nanocarriers for (bio)molecular drugs and contrast agent for bioimaging. They are formed by physically or chemically crosslinked polymer networks, characterized by a large and flexible surface available for multivalent bioconjugations. NGs can be produced with high yields and through-puts by pulsed electron-beam irradiation of dilute aqueous solutions of water-soluble biocompatible polymers. In this work, a carboxyl functionalized nanogel system (NG), generated by pulsed e-beam irradiation of a semi-dilute poly(N-vinyl pyrrolidone) (PVP) aqueous solution in the presence of acrylic acid, with an average diameter in the 60-70…

New insights on the mechanism of PVP nanogels radiation synthesis

In this work, the H2O2 build-up for several system compositions and irradiation conditions was investigated, by using the Ghormley triiodide method. Interestingly, the application of the method has revealed the occurrence of two concurrent reactions, the expected one responsible for the I3 - production (by reaction with the H2O2 formed upon irradiation) and one that is responsible for I3 - consumption. Both the concentrations of I3 - -forming and I3 - -consuming species are dose-dependent and polymer concentration-dependent. The kinetic study of the two reactions and some further experiments carried out with model molecules will be described. We believe that the results of this study can of…

Ionizing radiation synthesis of multifunctional nanogels for biomedical applications

Nanogels (NGs) are nanosized three-dimensional networks of crosslinked hydrophilic polymers. Their tunable chemical structure, physico-chemical properties and potential biocompatibility make them interesting substrates for the synthesis of “nanodevices” with therapeutic and/or diagnostic functions. In this PhD project, NGs were synthesized through pulsed e-beam irradiation of Poly-N-(Vinyl-Pyrrolidone) (PVP) aqueous solutions. The manufacturing process is fast and straightforward; it does not require the employment of organic solvents, surfactants, initiators or catalyst and guarantees high yields of the desired product. In dilute aqueous polymer solutions, ionizing radiation is mainly abso…

Radiation-engineered multifunctional nanogels: a versatile platform with theranostic capabilities for cancer

Under a rational desing, combining biologically active molecules, ligand to specific cell receptors and fluorescent, radioactive or paramagnetic labels into a single nano-object can bride the unique properties of the individual components and impruve conventional sensing, imaging and therapeutic efficaces.

Radiation Engineering of Xyloglucan Hydrogels

Xyloglucans (XGs) are interesting substrates for the production of scaffolds for tissue engineering, drug delivery depots and hydrogel dressings, thanks to their ability to gel in appropriate conditions, such as in the presence of hydro-alcoholic solvents or by addition of sugar molecules. Due to their natural source, they are characterized by high average molecular weights and broad molecular weight distributions. High energy irradiation is a suitable tool to reduce polysaccharides molecular weight without a dramatic alteration of the polymer chemical structure and gelation ability. In this work, the effect of the radiation dose on the molecular weight of a XG derived from Tamarind seeds i…

Insulin Nanogel as New Strategy for the Treatment of Alzheimer’s Disease

A growing body of evidence shows that Insulin, Insulin Receptor (IR) and IR signaling are involved in brain cognitive functions and their dysfunction is implicated in neuronal degeneration associated with Alzheimer's disease (AD). Thus, the administration of insulin to the brain could be a strategy for the prevention and treatment of AD disease. With this aim, we have designed, synthesized and characterized a nanogel system (NG) that can be used as substrate for the conjugation of insulin and/or fluorescent molecules relevant for their characterization. In particular, a carboxyl-functionalized poly(N-vinyl pyrrolidone) nanogel system, has been produced by ionizing radiation starting from th…

Gadolinium-chelating nanogels as MR contrast agents specifically targeting tumor cells

Aims and objectives Methods and materials Results Conclusion Personal information References

Synthetic and natural polymer nanoparticles as bio-imaging and therapeutic agent vectors

Water Extract of Cryphaea heteromalla (Hedw.) D. Mohr Bryophyte as a Natural Powerful Source of Biologically Active Compounds

Bryophytes comprise of the mosses, liverworts, and hornworts. Cryphaea heteromalla, (Hedw.) D. Mohr, is a non-vascular lower plant belonging to mosses group. To the date, the most chemically characterized species belong to the liverworts, while only 3.2% and 8.8% of the species belonging to the mosses and hornworts, respectively, have been investigated. In this work, we present Folin–Ciocalteu and oxygen radical absorbance capacity (ORAC) data related to crude extracts of C. heteromalla obtained by three di erent extraction solvents: pure water (WT), methanol:water (80:20 v/v) (MET), and ethanol:water (80:20 v/v) (ETH). The water extract proved to be the best solvent showing the highest con…

Synthesis and characterization of a new insulin conjugated nanogel for biomedical application

Insulin, a metabolic hormone involved in glucose metabolism, plays also a neuroprotective role in the central nervous system being able to revert the cytotoxic processes induced by Aβ42,a peptide involved in Alzheimer's disease. To reach the brain insulin have to across the BBB therefore an additional delivery strategy results to be necessary. For these aim we performed an insulin conjugated nanogels (NGs-In). Nanogels (NGs) have a great potential in the development of “smart” nanocarriers for (bio)molecular drugs and contrast agent for bioimaging. They are formed by physically or chemically crosslinked polymer networks, characterized by a large and flexible surface available for multivalen…

Sintesi di nanogeli per la veicolazione di insulina al cervello: una strategia per il trattamento della malattia di Alzheimer

I nanogeli sono nanoparticelle polimeriche reticolate idrofile. La struttura polimerica del nanogelo permette la coniugazione di molecole che possano esplicare azioni terapeutiche, diagnostiche e di indirizzamento attivo su siti bersaglio. Le caratteristiche di flessibilità e conformabilità del nanogelo, e delle sue maglie, ne favoriscono l’attraversamento delle barriere biologiche, l’interazione di eventuali ligandi esposti sulla superfice con i recettori target, un’azione protettiva nei confronti del principio attivo incorporato. L’irraggiamento con radiazioni ionizzanti di soluzioni acquose di polimeri è una metodologia sintetica interamente “water-based”, che garantisce rese elevate e c…

Insulin-nanogels: preliminary study in mouse for the treatment of Alzheimer's disease

A growing body of evidence shows that Insulin, Insulin Receptor (IR) and IR signalling are involved in brain cognitive functions and their dysfunction is implicated in Alzheimer’s disease (AD). Thus, administration of insulin could be a strategy for AD treatment. For this aim we have designed, synthesized and characterized a nanogel system (NG) that has been conjugated to insulin molecules (NG-In) (1) as new therapeutic approach against AD. In our preclinical studies in mice, intraperitoneal injection of fluorescent-labeled NG has allowed to determine the biodistribution of NG vs time in the whole body and its clearance through the kidneys and bladder. Furthermore, we have observed that mic…

Understanding generation of multifunctional nanogels in chemical-free e-beam irradation synthesis

Radiation engineered nanogels are the core of very promising theranostic nanodevoces. They can be produced starting from aqueous solutions of chemically inert polymers by pulsed e-beam irradiation.