The Experts below are selected from a list of 135 Experts worldwide ranked by ideXlab platform

Gaetano Giammona - One of the best experts on this subject based on the ideXlab platform.

  • Polyaminoacid doxorubicin prodrug micelles as highly selective therapeutics for targeted cancer therapy
    RSC Advances, 2016
    Co-Authors: Nicolo Mauro, Simona Campora, Giorgia Adamo, Cinzia Scialabba, Giulio Ghersi, Gaetano Giammona
    Abstract:

    An amphiphilic copolymer carrying high-dose doxorubicin (21% on a weight basis), PHEA–EDA–P,C–Doxo, was prepared by coupling doxorubicin with a biocompatible Polyaminoacid through a pH-sensitive spacer. Additional derivatization with 4-pentynoic acid endows it with self-assembling properties by means of π–π stacking. These micelles can be triggered to promptly release drug in lysosomes (∼40% in 12 h) through pH-dependent micelle hydrolysis after uptake. In vitro tests on co-cultures of cancer (MDA-MB 231) and normal (HB-2) breast cells proved that the conjugate was selectively internalized into the former rather than normal cells, exploiting the caveolae-dependent endocytosis pathway, explaining the selective cytotoxic effect toward cancer cells. Intracellular trafficking study of MDA-MB 231 showed that the delivery of the endocytosed drug occurs through the direct fusion of caveosomes with late lysosomes, triggering a massive release in the cytoplasm, bringing about cell death. Dose-effectiveness and mechanistic data indicate that PHEA–EDA–P,C–Doxo is endowed with a distinctive combination of selectivity and pharmacological potency (EC50 13 μM, Emax = 77% and EC50 > 25 μM, Emax = 21% for cancer and healthy cells respectively) that makes it an excellent candidate for future preclinical studies.

  • mechanical characterization of polysaccharide Polyaminoacid hydrogels as potential scaffolds for tissue regeneration
    Macromolecular Research, 2011
    Co-Authors: Pietro Matricardi, Giovanna Pitarresi, Fabio Salvatore Palumbo, Gaetano Giammona, Chiara Di Meo, Antonella Albanese, Tommasina Coviello, Claudia Cencetti, Calogero Fiorica
    Abstract:

    The mechanical properties of hydrogel scaffolds based on hyaluronic acid (HA) that were chemically crosslinked with α,β-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)-D,L-aspartamide (PHEA-EDA) were investigated. Variation of these properties as a function of three different PHEA-EDA amounts used to crosslink HA has been related to the reaction efficiency evaluated using a colorimetric assay. Moreover, the amount of unreacted amino groups that was still present in the hydrogels was related to the attachment behavior of human dermal fibroblasts to the hydrogel surface. The mechanical data and biological results suggest the suitability of the investigated hydrogels as scaffolds for the regeneration of soft tissues such as skin. Open image in new window

  • polysaccharide Polyaminoacid composite scaffolds for modified dna release
    International Journal of Pharmaceutics, 2009
    Co-Authors: Giovanna Pitarresi, Rossella Calabrese, Fabio Salvatore Palumbo, Mariano Licciardi, Gaetano Giammona
    Abstract:

    Abstract In this work composite polymeric films or sponges, based on hyaluronic acid (HA) covalently crosslinked with α,β-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)- d , l -aspartamide (PE), have been prepared and characterized as local gene delivery systems. In particular, HA/PE scaffolds have been loaded with PE/DNA interpolyelectrolyte complexes, employing PE as a macromolecular crosslinker for HA and as a non-viral vector for DNA. In vitro studies showed that HA/PE films and sponges have high compatibility with human dermal fibroblasts and they give a sustained DNA release, whose trend can be easily tailored by varying the crosslinking ratio between HA and PE. Electrophoresis analysis and transfection studies on B16-F10 cells revealed that DNA is released as a complex with PE and it retains its bioactivity.

  • scaffolds based on hyaluronan crosslinked with a Polyaminoacid novel candidates for tissue engineering application
    Journal of Biomedical Materials Research Part A, 2008
    Co-Authors: Giovanna Pitarresi, Fabio Salvatore Palumbo, Gennara Cavallaro, S. Fare', Gaetano Giammona
    Abstract:

    New porous scaffolds, with a suitable hydrolytic and enzymatic degradation, useful for tissue engineering applications have been obtained by a carbodiimide mediated reaction between hyaluronan (HA) and a synthetic polymer with a Polyaminoacid structure such as α,β-polyaspartylhydrazide (PAHy). Scaffolds with a different molar ratio between PAHy repeating units and HA repeating units have been prepared and characterized from a chemical and physicochemical point of view. Tests of indirect and direct cytotoxicity, cell adhesion, and spreading on these biomaterials have been performed by using murine L929 fibroblasts. The new biomaterials showed a good cell compatibility and ability to allow cell migration into the scaffolds as well as spreading on their surface. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008

  • Photocrosslinking of dextran and polyaspartamide derivatives: A combination suitable for colon-specific drug delivery
    'Elsevier BV', 2007
    Co-Authors: Giovanna Pitarresi, Fabio Salvatore Palumbo, Delia Mandracchia, Maria Antonietta Casadei, Patrizia Paolicelli, Gaetano Giammona
    Abstract:

    The aim of this study was to prepare and characterize novel hydrogels with polysaccharide-Polyaminoacid structure, able to undergo an enzymatic hydrolysis in the colon and potentially useful for treating inflammatory bowel diseases (1131)). Starting materials were methacrylated dextran (DEX-MA) and methacrylated alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHM). These polymers were photocrosslinked by exposure of their aqueous solutions at 313 nm without photoinitiators. Different samples, shaped as microparticles, were obtained as a function of polymer concentration and irradiation time. FT-IR analysis confirmed the occurrence of a co-crosslinking between DEX-MA and PHM in all experimental conditions. Size analysis evidenced a narrow particle distribution and swelling studies, performed in twice-distilled water and simulated gastrointestinal fluids, showed a good affinity of these hydrogels towards the aqueous medium. DEX-MA/PHM based hydrogels undergo a negligible chemical hydrolysis, whereas they are partially degraded by dextranase. In vitro biological assays showed cell compatibility of these samples. Beclomethasone dipropionate (BDP), a drug recently proposed for the treatment of 1131) was entrapped into a DEX-MA/PHM based hydrogel and its release was evaluated in the absence or in the presence of dextranase. Obtained release profiles suggest the potential use of BDP loaded DEX-MA/PHM based hydrogels for the treatment of IBD. (c) 2007 Elsevier B.V. All rights reserved

Giammona G. - One of the best experts on this subject based on the ideXlab platform.

  • A facile way to build up branched high functional Polyaminoacids with tunable physicochemical and biological properties
    'Elsevier BV', 2016
    Co-Authors: Mauro N., Fiorica C., Varvara' P., Di Prima G., Giammona G.
    Abstract:

    Here, for the first time, branched Polyaminoacids bearing \u3b1-amino acids as side functions, namely PAA-co-AA and PGA-co-AA, are prepared by heterophase ring opening of polysuccinimide (PSI) with l-arginine or glycine in aqueous environment and at controlled pH. The modulation of the pH of the reaction leads to high-molecular-weight copolymers with tunable functionalization and, as consequence, with tailor-made physicochemical properties. Furthermore, a branched Polyaminoacid carrying a preformed bioactive peptide (l-trileucine) and l-arginine as side pendants, named PATA-co-AA, was synthesized via a similar pathway thus leading to complex biomimetic materials potentially exploitable in several biomedical fields. Acid-base titrations, circular dichroism studies and spectrofluorimetric analysis show that the physicochemical behavior of this class of bioinspired copolymers can be predicted considering the starting features of the selected building blocks, implying that a careful choice of functional amino acids or peptides provides good chance for obtaining macromolecule libraries with selected properties

  • Polyaminoacid\u2013doxorubicin prodrug micelles as highly selective therapeutics for targeted cancer therapy
    'Royal Society of Chemistry (RSC)', 2016
    Co-Authors: Mauro N., Ghersi G., Campora S., Adamo G., Scialabba C., Giammona G.
    Abstract:

    An amphiphilic copolymer carrying high-dose doxorubicin (21% on a weight basis), PHEA\u2013EDA\u2013P,C\u2013Doxo, was prepared by coupling doxorubicin with a biocompatible Polyaminoacid through a pH-sensitive spacer. Additional derivatization with 4-pentynoic acid endows it with self-assembling properties by means of \u3c0\u2013\u3c0 stacking. These micelles can be triggered to promptly release drug in lysosomes ( 3c40% in 12 h) through pH-dependent micelle hydrolysis after uptake. In vitro tests on co-cultures of cancer (MDA-MB 231) and normal (HB-2) breast cells proved that the conjugate was selectively internalized into the former rather than normal cells, exploiting the caveolae-dependent endocytosis pathway, explaining the selective cytotoxic effect toward cancer cells. Intracellular trafficking study of MDA-MB 231 showed that the delivery of the endocytosed drug occurs through the direct fusion of caveosomes with late lysosomes, triggering a massive release in the cytoplasm, bringing about cell death. Dose-effectiveness and mechanistic data indicate that PHEA\u2013EDA\u2013P,C\u2013Doxo is endowed with a distinctive combination of selectivity and pharmacological potency (EC50 13 \u3bcM, Emax = 77% and EC50 > 25 \u3bcM, Emax = 21% for cancer and healthy cells respectively) that makes it an excellent candidate for future preclinical studies

  • POLYMERIC FLUORESCENT NANOPARTICLES BASED ON A POLYASPARTAMIDE FOR IMAGING APPLICATIONS: EVALUATION OF GALACTOSE TARGETING ON HEPG2 CELL INTERNALIZATION
    2014
    Co-Authors: Ef Craparo, Licciardi M., Giammona G., Cavallaro G., Sardo C, Conigliaro A, De Leo G, Alessandro R
    Abstract:

    In the field of nanomedicine, the use of polymeric fluorescent nanoparticles for in vitro and in vivo imaging is a promising application in order to evaluate passive as well as active targeting strategies [1]. In this work, the synthesis of an amphiphilic galactosylated polylactide-Polyaminoacid copolymer bearing rhodamine (RhB) moieties and its use for the preparation of polymeric fluorescent nanoparticles for potential in vitro and in vivo imaging applications are described. To do this, firstly, a fluorescent derivative of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) was obtained by chemical reaction of PHEA with RhB. Then, a galactosylated derivative of polyethylene glycol, the O-(2-aminoethyl)-O’-galactosyl polyethylene glycol (GAL-PEG-NH2) was obtained by a reductive amination of lactose with primary amine function of poly(ethylene glycol)bis(amine) (H2N-PEG-NH2) in the presence of sodium cyanoborohydride. The fluorescent galactosylated polylactide-Polyaminoacid conjugate was obtained by chemical reaction of PHEA-RhB with polylactic acid (PLA), and subsequent reaction with GAL-PEG-NH2, obtaining PHEA-RhB-PLA-PEG-GAL copolymer [2]. Starting from this copolymer, liver-targeted fluorescent nanoparticles, were successfully prepared by high pressure homogenization– solvent evaporation method [2]. Fluorescenti nanoparticles have nanoscaled size and spherical shape as showed by Dinamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM) analyses. Moreover, thanks to the fluorescence given by covalently-linked RhB, by confocal microscopy studies it was demonstrated that these nanoparticles bearing GAL moieties interact with HepG2 cells that are positive for the asialoglycoprotein receptor (ASGP-R), while these do not interact with HeLa cells that are negative for the same receptor, demonstrating the contributor of ASGPR to the internalization process. [1] Vollrath A, S. Schubert, U.S. Schubert, Fluorescence imaging of cancer tissue based on metal-free polimeric nanopaticles - A review, J Mat Chem. 1, 1994 (2013). [2] E.F. Craparo, G. Teresi, M.C. Ognibene, M.P. Casaletto, M.L. Bondì, G. Cavallaro. J Nanoparticle Res. 12, 2629 (2010)

  • Galactosylated Micelles for a Ribavirin Prodrug Targeting to Hepatocytes
    'American Chemical Society (ACS)', 2013
    Co-Authors: Craparo E., Giammona G., Pitarresi G., Triolo D., Cavallaro G.
    Abstract:

    Polymeric micelles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors, that is, ASGPR, were prepared starting from a galactosylated polylactide-Polyaminoacid conjugate. This latter was obtained by chemical reaction of \u3b1,\u3b2-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-DL-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, obtaining PHEA-EDA-PLAGAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, that is, RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. Liver-targeted RBV tripalmitate-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometric size. By in vitro experiments, the specificity of RBV tripalmitate-loaded PHEA-EDA-PLA-GAL micelles toward HepG2 was demonstrated by using a competitive inhibition assay in the presence of free GAL. This finding raises hope in terms of future micelles-based liver-targeted drug delivery strategy for the hepatitis C treatment

  • A Fibrillar Biodegradable Scaffold for Blood Vessels Tissue Engineering
    country:IT, 2012
    Co-Authors: Fiorica C., Giammona G., Pitarresi G., Rigogliuso S., Palumbo F., Ghersi G.
    Abstract:

    In recent years there has been a growing interest for the development of tubular scaffolds employed to assist the replacement of small blood vessels. Materials designed for this purpose need to be biodegradable, have good mechanical properties and improve cell adhesion, proliferation and differentiation. To obtain biomaterials with these properties, electrospinning seems to be one of the most useful technique. Several biodegradable synthetic polymers or constituents of the extracellular matrix (ECM) have been electrospun showing optimal mechanical properties and biodegradability. However, such polymers are lacking in versatile chemical structure affordable to immobilize growth factors or chemokines. The glycosaminoglycan heparin is able to bind several growth factors like vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and, when grafted onto the scaffold surface it is able to attract cells thus improving their proliferation and differentiation. Aim of this research was the production and the preliminary in vitro biological characterization of a new biodegradable material, obtained by electrospun a Polyaminoacid-graft-polyester copolymer. The electrospun biomaterial has been successfully grafted with heparin exploiting the better chemical reactivity of the Polyaminoacid portions of the graft copolymer. Then its morphology has been investigated by scanning electron microscopy (SEM) and the potential biodegradability of the material has been studied until 60 days. Preliminary biological data in vitro, on human endothelial cells, show a good compatibility of the scaffold obtained by electrospinning, with regard to cell adhesion and proliferation. Experiments are in progress to evaluate the effects of heparin on cell differentiation

Giovanna Pitarresi - One of the best experts on this subject based on the ideXlab platform.

  • mechanical characterization of polysaccharide Polyaminoacid hydrogels as potential scaffolds for tissue regeneration
    Macromolecular Research, 2011
    Co-Authors: Pietro Matricardi, Giovanna Pitarresi, Fabio Salvatore Palumbo, Gaetano Giammona, Chiara Di Meo, Antonella Albanese, Tommasina Coviello, Claudia Cencetti, Calogero Fiorica
    Abstract:

    The mechanical properties of hydrogel scaffolds based on hyaluronic acid (HA) that were chemically crosslinked with α,β-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)-D,L-aspartamide (PHEA-EDA) were investigated. Variation of these properties as a function of three different PHEA-EDA amounts used to crosslink HA has been related to the reaction efficiency evaluated using a colorimetric assay. Moreover, the amount of unreacted amino groups that was still present in the hydrogels was related to the attachment behavior of human dermal fibroblasts to the hydrogel surface. The mechanical data and biological results suggest the suitability of the investigated hydrogels as scaffolds for the regeneration of soft tissues such as skin. Open image in new window

  • polysaccharide Polyaminoacid composite scaffolds for modified dna release
    International Journal of Pharmaceutics, 2009
    Co-Authors: Giovanna Pitarresi, Rossella Calabrese, Fabio Salvatore Palumbo, Mariano Licciardi, Gaetano Giammona
    Abstract:

    Abstract In this work composite polymeric films or sponges, based on hyaluronic acid (HA) covalently crosslinked with α,β-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)- d , l -aspartamide (PE), have been prepared and characterized as local gene delivery systems. In particular, HA/PE scaffolds have been loaded with PE/DNA interpolyelectrolyte complexes, employing PE as a macromolecular crosslinker for HA and as a non-viral vector for DNA. In vitro studies showed that HA/PE films and sponges have high compatibility with human dermal fibroblasts and they give a sustained DNA release, whose trend can be easily tailored by varying the crosslinking ratio between HA and PE. Electrophoresis analysis and transfection studies on B16-F10 cells revealed that DNA is released as a complex with PE and it retains its bioactivity.

  • scaffolds based on hyaluronan crosslinked with a Polyaminoacid novel candidates for tissue engineering application
    Journal of Biomedical Materials Research Part A, 2008
    Co-Authors: Giovanna Pitarresi, Fabio Salvatore Palumbo, Gennara Cavallaro, S. Fare', Gaetano Giammona
    Abstract:

    New porous scaffolds, with a suitable hydrolytic and enzymatic degradation, useful for tissue engineering applications have been obtained by a carbodiimide mediated reaction between hyaluronan (HA) and a synthetic polymer with a Polyaminoacid structure such as α,β-polyaspartylhydrazide (PAHy). Scaffolds with a different molar ratio between PAHy repeating units and HA repeating units have been prepared and characterized from a chemical and physicochemical point of view. Tests of indirect and direct cytotoxicity, cell adhesion, and spreading on these biomaterials have been performed by using murine L929 fibroblasts. The new biomaterials showed a good cell compatibility and ability to allow cell migration into the scaffolds as well as spreading on their surface. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008

  • a new biodegradable and biocompatible hydrogel with Polyaminoacid structure
    International Journal of Pharmaceutics, 2007
    Co-Authors: Giovanna Pitarresi, Filippo Saiano, Gennara Cavallaro, Delia Mandracchia, Fabio Salvatore Palumbo
    Abstract:

    The preparation and physicochemical and biological characterization of a novel Polyaminoacid hydrogel have been reported. The alpha,beta-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) has been used as a starting polymer for a derivatization reaction with methacrylic anhydride (MA) to give rise to the methacrylate derivative named PHM. Photocrosslinking of PHM has been performed in aqueous solution at 313 nm and in the absence of toxic initiators. PHM-based hydrogel has been characterized by scanning electron microscopy, X-ray diffractometry, swelling measurements in aqueous media; the degradation of PHM-based hydrogel has been evaluated as a function of time in the absence or in the presence of esterase. Besides, the biocompatibility of this hydrogel and of its degradation products has been evaluated by performing in vitro assays on human chronic myelogenous leukaemia cells (K-562), chosen as a model cell line. Finally, ATR-FTIR measurements have showed that interaction between PHM-based hydrogel and each of four plasma proteins (albumin, gamma-globulin, transferrin and fibrinogen) does not cause change in protein conformation thus supporting its potential use as a material to prepare parenteral drug delivery systems.

  • Photocrosslinking of dextran and polyaspartamide derivatives: A combination suitable for colon-specific drug delivery
    'Elsevier BV', 2007
    Co-Authors: Giovanna Pitarresi, Fabio Salvatore Palumbo, Delia Mandracchia, Maria Antonietta Casadei, Patrizia Paolicelli, Gaetano Giammona
    Abstract:

    The aim of this study was to prepare and characterize novel hydrogels with polysaccharide-Polyaminoacid structure, able to undergo an enzymatic hydrolysis in the colon and potentially useful for treating inflammatory bowel diseases (1131)). Starting materials were methacrylated dextran (DEX-MA) and methacrylated alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHM). These polymers were photocrosslinked by exposure of their aqueous solutions at 313 nm without photoinitiators. Different samples, shaped as microparticles, were obtained as a function of polymer concentration and irradiation time. FT-IR analysis confirmed the occurrence of a co-crosslinking between DEX-MA and PHM in all experimental conditions. Size analysis evidenced a narrow particle distribution and swelling studies, performed in twice-distilled water and simulated gastrointestinal fluids, showed a good affinity of these hydrogels towards the aqueous medium. DEX-MA/PHM based hydrogels undergo a negligible chemical hydrolysis, whereas they are partially degraded by dextranase. In vitro biological assays showed cell compatibility of these samples. Beclomethasone dipropionate (BDP), a drug recently proposed for the treatment of 1131) was entrapped into a DEX-MA/PHM based hydrogel and its release was evaluated in the absence or in the presence of dextranase. Obtained release profiles suggest the potential use of BDP loaded DEX-MA/PHM based hydrogels for the treatment of IBD. (c) 2007 Elsevier B.V. All rights reserved

Fabio Salvatore Palumbo - One of the best experts on this subject based on the ideXlab platform.

  • mechanical characterization of polysaccharide Polyaminoacid hydrogels as potential scaffolds for tissue regeneration
    Macromolecular Research, 2011
    Co-Authors: Pietro Matricardi, Giovanna Pitarresi, Fabio Salvatore Palumbo, Gaetano Giammona, Chiara Di Meo, Antonella Albanese, Tommasina Coviello, Claudia Cencetti, Calogero Fiorica
    Abstract:

    The mechanical properties of hydrogel scaffolds based on hyaluronic acid (HA) that were chemically crosslinked with α,β-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)-D,L-aspartamide (PHEA-EDA) were investigated. Variation of these properties as a function of three different PHEA-EDA amounts used to crosslink HA has been related to the reaction efficiency evaluated using a colorimetric assay. Moreover, the amount of unreacted amino groups that was still present in the hydrogels was related to the attachment behavior of human dermal fibroblasts to the hydrogel surface. The mechanical data and biological results suggest the suitability of the investigated hydrogels as scaffolds for the regeneration of soft tissues such as skin. Open image in new window

  • polysaccharide Polyaminoacid composite scaffolds for modified dna release
    International Journal of Pharmaceutics, 2009
    Co-Authors: Giovanna Pitarresi, Rossella Calabrese, Fabio Salvatore Palumbo, Mariano Licciardi, Gaetano Giammona
    Abstract:

    Abstract In this work composite polymeric films or sponges, based on hyaluronic acid (HA) covalently crosslinked with α,β-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)- d , l -aspartamide (PE), have been prepared and characterized as local gene delivery systems. In particular, HA/PE scaffolds have been loaded with PE/DNA interpolyelectrolyte complexes, employing PE as a macromolecular crosslinker for HA and as a non-viral vector for DNA. In vitro studies showed that HA/PE films and sponges have high compatibility with human dermal fibroblasts and they give a sustained DNA release, whose trend can be easily tailored by varying the crosslinking ratio between HA and PE. Electrophoresis analysis and transfection studies on B16-F10 cells revealed that DNA is released as a complex with PE and it retains its bioactivity.

  • scaffolds based on hyaluronan crosslinked with a Polyaminoacid novel candidates for tissue engineering application
    Journal of Biomedical Materials Research Part A, 2008
    Co-Authors: Giovanna Pitarresi, Fabio Salvatore Palumbo, Gennara Cavallaro, S. Fare', Gaetano Giammona
    Abstract:

    New porous scaffolds, with a suitable hydrolytic and enzymatic degradation, useful for tissue engineering applications have been obtained by a carbodiimide mediated reaction between hyaluronan (HA) and a synthetic polymer with a Polyaminoacid structure such as α,β-polyaspartylhydrazide (PAHy). Scaffolds with a different molar ratio between PAHy repeating units and HA repeating units have been prepared and characterized from a chemical and physicochemical point of view. Tests of indirect and direct cytotoxicity, cell adhesion, and spreading on these biomaterials have been performed by using murine L929 fibroblasts. The new biomaterials showed a good cell compatibility and ability to allow cell migration into the scaffolds as well as spreading on their surface. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008

  • a new biodegradable and biocompatible hydrogel with Polyaminoacid structure
    International Journal of Pharmaceutics, 2007
    Co-Authors: Giovanna Pitarresi, Filippo Saiano, Gennara Cavallaro, Delia Mandracchia, Fabio Salvatore Palumbo
    Abstract:

    The preparation and physicochemical and biological characterization of a novel Polyaminoacid hydrogel have been reported. The alpha,beta-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) has been used as a starting polymer for a derivatization reaction with methacrylic anhydride (MA) to give rise to the methacrylate derivative named PHM. Photocrosslinking of PHM has been performed in aqueous solution at 313 nm and in the absence of toxic initiators. PHM-based hydrogel has been characterized by scanning electron microscopy, X-ray diffractometry, swelling measurements in aqueous media; the degradation of PHM-based hydrogel has been evaluated as a function of time in the absence or in the presence of esterase. Besides, the biocompatibility of this hydrogel and of its degradation products has been evaluated by performing in vitro assays on human chronic myelogenous leukaemia cells (K-562), chosen as a model cell line. Finally, ATR-FTIR measurements have showed that interaction between PHM-based hydrogel and each of four plasma proteins (albumin, gamma-globulin, transferrin and fibrinogen) does not cause change in protein conformation thus supporting its potential use as a material to prepare parenteral drug delivery systems.

  • Photocrosslinking of dextran and polyaspartamide derivatives: A combination suitable for colon-specific drug delivery
    'Elsevier BV', 2007
    Co-Authors: Giovanna Pitarresi, Fabio Salvatore Palumbo, Delia Mandracchia, Maria Antonietta Casadei, Patrizia Paolicelli, Gaetano Giammona
    Abstract:

    The aim of this study was to prepare and characterize novel hydrogels with polysaccharide-Polyaminoacid structure, able to undergo an enzymatic hydrolysis in the colon and potentially useful for treating inflammatory bowel diseases (1131)). Starting materials were methacrylated dextran (DEX-MA) and methacrylated alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHM). These polymers were photocrosslinked by exposure of their aqueous solutions at 313 nm without photoinitiators. Different samples, shaped as microparticles, were obtained as a function of polymer concentration and irradiation time. FT-IR analysis confirmed the occurrence of a co-crosslinking between DEX-MA and PHM in all experimental conditions. Size analysis evidenced a narrow particle distribution and swelling studies, performed in twice-distilled water and simulated gastrointestinal fluids, showed a good affinity of these hydrogels towards the aqueous medium. DEX-MA/PHM based hydrogels undergo a negligible chemical hydrolysis, whereas they are partially degraded by dextranase. In vitro biological assays showed cell compatibility of these samples. Beclomethasone dipropionate (BDP), a drug recently proposed for the treatment of 1131) was entrapped into a DEX-MA/PHM based hydrogel and its release was evaluated in the absence or in the presence of dextranase. Obtained release profiles suggest the potential use of BDP loaded DEX-MA/PHM based hydrogels for the treatment of IBD. (c) 2007 Elsevier B.V. All rights reserved

Cavallaro G. - One of the best experts on this subject based on the ideXlab platform.

  • GALACTOSE-DECORATED POLYMERIC CARRIERS FOR HEPATOCYTE-SELECTIVE DRUG TARGETING
    2015
    Co-Authors: Craparo E., Cavallaro G.
    Abstract:

    In this paper, the current available strategies to realize galactose-decorated nanostructured polymeric systems are summarized. These carriers are designed in order to obtain targeted drug delivery to hepatocytes via galactose (GAL) moieties, i.e., for the treatment of viral hepatitis or liver cancer that are the greater causes of global disability and mortality. Usually, the main followed strategy to obtain galactosylated polymeric carriers is to use galactosylated copolymers. The chemical modifications of preformed polymers with sugar-containing reagents is followed for obtaining lactosaminated human albumin, galactosylated phospholipid-Polyaminoacid and polylactide (PLA)- Polyaminoacid conjugates obtained from \u3b1,\u3b2-poly(N-2- hydroxyethyl)-D,L-aspartamide (PHEA) or lactosaminated carboxymethyl chitosan (CMC). Galactosylated polymers are also obtained via the polymerization of GALbearing monomers, that is for obtaining galactosylated polycarbonates. Finally, the surface galactosylation of preformed polymeric carriers is an alternative strategy that can be used to obtain a GAL-decorated system, that is for obtaining dendrimers based on polyamidoamine (PAMAM)-GAL conjugates

  • POLYMERIC FLUORESCENT NANOPARTICLES BASED ON A POLYASPARTAMIDE FOR IMAGING APPLICATIONS: EVALUATION OF GALACTOSE TARGETING ON HEPG2 CELL INTERNALIZATION
    2014
    Co-Authors: Ef Craparo, Licciardi M., Giammona G., Cavallaro G., Sardo C, Conigliaro A, De Leo G, Alessandro R
    Abstract:

    In the field of nanomedicine, the use of polymeric fluorescent nanoparticles for in vitro and in vivo imaging is a promising application in order to evaluate passive as well as active targeting strategies [1]. In this work, the synthesis of an amphiphilic galactosylated polylactide-Polyaminoacid copolymer bearing rhodamine (RhB) moieties and its use for the preparation of polymeric fluorescent nanoparticles for potential in vitro and in vivo imaging applications are described. To do this, firstly, a fluorescent derivative of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) was obtained by chemical reaction of PHEA with RhB. Then, a galactosylated derivative of polyethylene glycol, the O-(2-aminoethyl)-O’-galactosyl polyethylene glycol (GAL-PEG-NH2) was obtained by a reductive amination of lactose with primary amine function of poly(ethylene glycol)bis(amine) (H2N-PEG-NH2) in the presence of sodium cyanoborohydride. The fluorescent galactosylated polylactide-Polyaminoacid conjugate was obtained by chemical reaction of PHEA-RhB with polylactic acid (PLA), and subsequent reaction with GAL-PEG-NH2, obtaining PHEA-RhB-PLA-PEG-GAL copolymer [2]. Starting from this copolymer, liver-targeted fluorescent nanoparticles, were successfully prepared by high pressure homogenization– solvent evaporation method [2]. Fluorescenti nanoparticles have nanoscaled size and spherical shape as showed by Dinamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM) analyses. Moreover, thanks to the fluorescence given by covalently-linked RhB, by confocal microscopy studies it was demonstrated that these nanoparticles bearing GAL moieties interact with HepG2 cells that are positive for the asialoglycoprotein receptor (ASGP-R), while these do not interact with HeLa cells that are negative for the same receptor, demonstrating the contributor of ASGPR to the internalization process. [1] Vollrath A, S. Schubert, U.S. Schubert, Fluorescence imaging of cancer tissue based on metal-free polimeric nanopaticles - A review, J Mat Chem. 1, 1994 (2013). [2] E.F. Craparo, G. Teresi, M.C. Ognibene, M.P. Casaletto, M.L. Bondì, G. Cavallaro. J Nanoparticle Res. 12, 2629 (2010)

  • Galactosylated Micelles for a Ribavirin Prodrug Targeting to Hepatocytes
    'American Chemical Society (ACS)', 2013
    Co-Authors: Craparo E., Giammona G., Pitarresi G., Triolo D., Cavallaro G.
    Abstract:

    Polymeric micelles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors, that is, ASGPR, were prepared starting from a galactosylated polylactide-Polyaminoacid conjugate. This latter was obtained by chemical reaction of \u3b1,\u3b2-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-DL-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, obtaining PHEA-EDA-PLAGAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, that is, RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. Liver-targeted RBV tripalmitate-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometric size. By in vitro experiments, the specificity of RBV tripalmitate-loaded PHEA-EDA-PLA-GAL micelles toward HepG2 was demonstrated by using a competitive inhibition assay in the presence of free GAL. This finding raises hope in terms of future micelles-based liver-targeted drug delivery strategy for the hepatitis C treatment

  • NOVEL COMPOSED GALACTOSYLATED NANODEVICES CONTAINING A RIBAVIRIN PRODRUG AS HEPATIC CELL-TARGETED CARRIERS FOR HCV TREATMENT
    2013
    Co-Authors: Craparo E., Licciardi M., Teresi G., Bondi' M., Cavallaro G.
    Abstract:

    In this paper, we describe the preparation of liver-targeted nanoparticles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors in the liver (i.e., ASGPR in hepatocytes). These particles were obtained starting from a galactosylated phospholipid-Polyaminoacid conjugate. This latter was obtained by chemical reaction of ALPHA, BETA -poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-DL-aspartamide (PHEA-EDA) with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl) sodium salt (DPPE), and subsequent reaction with lactose, obtaining PHEA-EDA-DPPE-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, i.e., RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. RBV tripalmitate-loaded nanoparticles were obtained starting from PHEA-EDA-DPPE-GAL copolymer by using the dialysis method. These particles showed spherical shape and nanometric size. By in vitro experiments the absence of haemolytic activity of RBV tripalmitate-loaded PHEA-EDA-DPPE-GAL nanoparticles and their specificity toward HepG2 were demonstrated by using a competitive inhibition assay in the presence of free GAL and assessing nanoparticle uptake in the presence of free GAL and/or non-galactosylated nanoparticles. This finding raises hope in terms of future nanoparticle-based liver-targeted drug delivery strategy for the hepatitis C treatment

  • COLLOIDAL VECTORS WITH Polyaminoacid STRUCTURE FOR ORAL RELEASE OF PEPTIDES AND PROTEINS AND METHOD FOR THEIR PRODUCTION
    2008
    Co-Authors: Licciardi M., Giammona G., Cavallaro G., Pitarresi G.
    Abstract:

    The present invention concerns colloidal vectors with Polyaminoacid structure for oral release of peptides and proteins and a method for their production. Specifically, the invention concerns systems for the release of active substances, specifically peptides and proteins, by means of their incorporation in nanoparticles, nano-aggregates or complexes based on properly derivatized synthetic Polyaminoacids. These polymeric systems are proposed to release peptide drugs or proteins from oral dosage forms in an effective manner, besides increasing the physicochemical stability of proteins in liquid or solid pharmaceutical dosage forms