SELF-ASSEMBLING POLY(HYDROXYETHYL ASPARTAMIDE)-GRAFT POLYMETHACRYLATE COPOLYMERS OBTAINED BY ATOM TRANSFER RADICAL POLYMERIZATION

Nuovi derivati poliaspartammidici per la veicolazione di proteine della terapia antitumorale

A new hyaluronic acid pH sensitive derivative obtained by ATRP for potential oral administration of proteins

Atom transfer radical polymerization (ATRP) has been successfully employed to obtain a new derivative of hyaluronic acid (HA) able to change its solubility as a function of external pH and then to be potentially useful for intestinal release of bioactive molecules, included enzymes and proteins. In particular, a macroinitiator has been prepared by linking 2-bromo-2-methypropionic acid (BMP) to the amino groups of ethylenediamino derivative of tetrabutyl ammonium salt of HA (HA-TBA-EDA). This macroinititor, named HA-TBA-EDA-BMP has been used for the ATRP of sodium methacrylate (MANa) using a complex of Cu(I) and 2,2'-bipyridyl (Byp) as a catalyst. The resulting copolymer, named HA-EDA-BMP-MA…

PEG-benzofulvene copolymer hydrogels for antibody delivery.

A new amphiphilic copolymer have been synthesized starting from the hydrosoluble polyaspartylhydrazide (PAHy) polymer, by grafting both hydrophilic PEG(2000) chains and hydrophobic palmitic acid (C(16)) moieties on polymer backbone, and the structure of obtained PAHy-PEG(2000)-C(16) copolymer have been characterized by 2D (1)H/(13)C NMR experiments. PAHy-PEG(2000)-C(16) copolymer showed the ability of self-assembling in aqueous media giving a core-shell structure and resulted potentially useful for encapsulating and dissolving hydrophobic drug. The formation of micellar core-shell structure has been investigated by 2D (1)H NMR NOESY experiments. The presence of cross-peaks for protons of C(…

TABLET DI ACIDO IALURONICO FUNZIONALIZZATO CON CATENE IDROFOBICHE PER IL RILASCIO LOCOREGIONALE DI PACLITAXEL

BIOCOMPATIBLE POLYCATIONS FOR GENE DELIVERY

HYALURONIC ACID-graft-ELASTIN BASED SCAFFOLDS FOR POTENTIAL TISSUE ENGINEERING APPLICATIONS

NEW SELF-ASSEMBLING POLYASPARTYLHYDRAZIDE COPOLYMER MICELLES FOR ANTICANCER DRUG DELIVERY.

A new amphiphilic copolymer have been synthesized starting from the hydrosoluble polyaspartylhydrazide (PAHy) polymer, by grafting both hydrophilic PEG(2000) chains and hydrophobic palmitic acid (C(16)) moieties on polymer backbone, and the structure of obtained PAHy-PEG(2000)-C(16) copolymer have been characterized by 2D (1)H/(13)C NMR experiments. PAHy-PEG(2000)-C(16) copolymer showed the ability of self-assembling in aqueous media giving a core-shell structure and resulted potentially useful for encapsulating and dissolving hydrophobic drug. The formation of micellar core-shell structure has been investigated by 2D (1)H NMR NOESY experiments. The presence of cross-peaks for protons of C(…

Dexamethasone dipropionate loaded nanoparticles of α-elastin-g-PLGA for potential treatment of restenosis.

A graft copolymer of α-elastin with poly(lactic-co-glycolic) acid (PLGA) has been synthesized and successfully employed to produce nanoparticles. Exploiting the known biological activity of α-elastin to promote the maintenance of smooth muscle cells (SMCs) contractile phenotype and the antiproliferative effect of glucocorticoids, the aim of this research was to produce drug-loaded nanoparticles suitable for potential treatment of restenosis. In particular, nanoparticles of α-elastin-g-PLGA with a mean size of 200 nm have been produced and loaded with dexamethasone dipropionate (10% w/w), chosen as a model drug that inhibits proliferation of vascular SMCs. These nanoparticles are able to pro…

Inulin derivatives obtained via enhanced microwave synthesis as potential drug delivery system.

Injectable in situ forming microgels of hyaluronic acid-g-polylactic acid for methylprednisolone release

Abstract A hydrophobic derivative of hyaluronic acid (HA), obtained by grafting polylactic acid (PLA) to the polysaccharide, has been exploited to produce injectable in situ forming microgels. First of all, self assembling properties of HA-g-PLA copolymer have been evaluated by determining the critical aggregation concentration (CAC) value, then this copolymer has been dissolved in a mixture water/NMP 5:2 v/v with a concentration greater than CAC. When solutions at 1% or 2% w/v were injected into Dulbecco phosphate buffer solution (DPBS) pH 7.4, microgels promptly are formed. Their stability in DPBS pH 7.4 in the absence or in the presence of hyaluronidase and cell compatibility have been e…

SYNTHESIS AND PHYSICO-CHEMICAL CHARACTERIZATION OF NEW PHEA-GRAFT COPOLYMERS OBTAINED BY ARTP

Medicated hydrogels of hyaluronic acid derivatives for use in orthopedic field

Polyaspartamide-graft- Polymethacrylate Nanoparticles for Doxorubicin Delivery

A new PHEA-IB-PMANa + copolymer has been synthesized and its pH-induced self-assembly has been investigated in an aqueous medium. PHEA-IB-PMANa + formed nanoparticles with diameters from 25 to 50 nm upon protonation of the carboxylic acid moieties dislocated along the grafted polymethacrylate sodium salt side chains. The physico-chemical characterization of the nanoparticles was performed using light scattering, zeta-potential measurements, SEM, and AFM. Doxorubicin-loaded nanoparticles were prepared and drug release profiles were evaluated under conditions mimicking physiological media. A biological characterization was carried out by testing the cytotoxicity on Caco-2 cells, and cellular …

In situ forming hydrogels of hyaluronic acid and inulin derivatives for cartilage regeneration.

An in situ forming hydrogel obtained by crosslinking of amino functionalized hyaluronic acid derivatives with divinylsulfone functionalized inulin (INU-DV) has been here designed and characterized. In particular two hyaluronic acid derivatives bearing respectively a pendant ethylenediamino (EDA) portion (HA-EDA) and both EDA and octadecyl pendant groups (HA-EDA-C18) were crosslinked through an azo-Michael reaction with INU-DV. Gelation time and consumption of DV portions have been evaluated on hydrogel obtained using HA-EDA and HA-EDA-C18 derivatives with a concentration of 3% w/v and a ratio 80/20 w/w respect to the crosslinker INU-DV. The presence of pendant C18 chains improves mechanical…

Medicated hydrogels of hyaluronic acid derivatives for use in orthopedic field.

Physical hydrogels have been obtained from hyaluronic acid derivatized with polylactic acid in the presence or in the absence of polyethylene glycol chains. They have been extemporarily loaded with antibacterial agents, such as vancomycin and tobramycin. These medicated hydrogels have been used to coat titanium disks (chosen as simple model of orthopedic prosthesis) and in vitro studies in simulated physiological fluid have been performed as a function of time and for different drug loading and polymer concentration values. Sterilization process performed on the hydrogels does not change their rheological behavior and release properties as well as the chemical structure of starting copolyme…

PHEA-graft-polybutylmethacrylate copolymer microparticles for delivery of hydrophobic drugs.

Abstract Polymeric microparticles encapsulating two model hydrophobic drugs, beclomethasone dipropionate (BDP) and flutamide (FLU) were prepared by using the high pressure homogenization-solvent evaporation method starting from a oil-in-water emulsion. For the preparation of polymeric microparticles a α,β-poly(N-2-hydroxyethyl)- d , l -aspartamide (PHEA) graft copolymer with comb like structure was properly synthesized via grafting from atom transfer radical polymerization (ATRP) technique, by using two subsequent synthetic steps. In the first step a polymeric multifunctional macroinitiator was obtained by the conjugation of a proper number of 2-bromoisobutyryl bromide (BIB) residues to the…

Construction and evaluation of sponge scaffolds from hyaluronic acid derivatives for potential cartilage regeneration

A two or one pot synthesis has been used for the reaction of hyaluronic acid (HA) with octadecylamine (C-18) and hydrazine (Hy). In both cases, the chemical derivatization involved primary hydroxyl groups of hyaluronic acid and not its carboxyl groups, whose presence is important for receptor interaction. In this way, Hy-HA-C-18 derivatives have been obtained with appropriate hydrophobic and hydrophilic character. Their ability to form homogeneous physical hydrogels has been evaluated as well as the possibility to obtain porous sponges through salt leaching technology. Sponges showing the highest porosity, potentially compatible with cell entrapment, have been characterized with regard to t…

ANTICANCER RELEASING FILMS AND POROUS SCAFFOLDS BASED ON PHYSICALLY ASSEMBLED HYALURONIC ACID DERIVATIVES

Polyaspartamide-graft-polymethacrylate nanoparticles for doxorubicin delivery

BIODEGRADABLE POLYASPARTAMIDE-GRAFT-POLYESTER COPOLYMER FOR VASCULAR REGENERATION

HYDROGELS OF HYALURONIC ACID-GRAFT-alfa-ELASTIN AS EXTRACELLULAR MATRIX SUBSTITUTES

PREPARATION AND CHARACTERIZATION OF NEW PHEA-GRAFT-POLYMETHACRYLATE NANOPARTICLES.

NEW PHEA COPOLYMERS BEARING GRAFT POLYMETHACRYLIC ACID CHAINS AS CARRIER FOR ENDOSTATIN

New Self-Assembling Polyaspartamide-Based Brush Copolymers Obtained by Atom Transfer Radical Polymerization

A simple and efficient method for the synthesis of polyaspartamide-based brush copolymers using Atom Transfer Radical Polymerization (ATRP) is here presented. The syntheses were performed by using two subsequent steps. In the first step the macroinitiator was obtained by the conjugation of a proper number of 2-bromoisobutyryl bromide (BIB) residues to the R, -poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) side chains, obtaining the PHEA-BIB copolymer. PHEA-BIB copolymer was used as “multi-functional macroinitiator” for the polymerization via ATRP of hydrophilic methacrylic monomers, such as methacrylic acid (MA), obtaining PHEA-IB-poly(MA) copolymer, sodium methacrylate (MANa+), obtaining PH…

BIOCOMPATIBLE PHEA-SPERMINE COPOLYMERS FOR GENE DELIVERY