Publications by authors named "Maria Grazia Cascone"

18 Publications

  • Page 1 of 1

Targeting Cancer Cells Overexpressing Folate Receptors with New Terpolymer-Based Nanocapsules: Toward a Novel Targeted DNA Delivery System for Cancer Therapy.

Biomedicines 2021 Sep 21;9(9). Epub 2021 Sep 21.

Department of Civil and Industrial Engineering, University of Pisa, 56122 Pisa, Italy.

Chemotherapeutics represent the standard treatment for a wide range of cancers. However, these agents also affect healthy cells, thus leading to severe off-target effects. Given the non-selectivity of the commonly used drugs, any increase in the selective tumor tissue uptake would represent a significant improvement in cancer therapy. Recently, the use of gene therapy to completely remove the lesion and avoid the toxicity of chemotherapeutics has become a tendency in oncotherapy. Ideally, the genetic material must be safely transferred from the site of administration to the target cells, without involving healthy tissues. This can be achieved by encapsulating genes into non-viral carriers and modifying their surface with ligands with high selectivity and affinity for a relevant receptor on the target cells. Hence, in this work we evaluate the use of terpolymer-based nanocapsules for the targeted delivery of DNA toward cancer cells. The surface of the nanocapsules is decorated with folic acid to actively target the folate receptors overexpressed on a variety of cancer cells. The nanocapsules demonstrate a good ability of encapsulating and releasing DNA. Moreover, the presence of the targeting moieties on the surface of the nanocapsules favors cell uptake, opening up the possibility of more effective therapies.
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http://dx.doi.org/10.3390/biomedicines9091275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471118PMC
September 2021

Development of Biomimetic Alginate/Gelatin/Elastin Sponges with Recognition Properties toward Bioactive Peptides for Cardiac Tissue Engineering.

Biomimetics (Basel) 2020 Dec 11;5(4). Epub 2020 Dec 11.

Department of Civil and Industrial Engineering, University of Pisa, Largo Lucio Lazzarino, 56126 Pisa, Italy.

In recent years, there has been an increasing interest toward the covalent binding of bioactive peptides from extracellular matrix proteins on scaffolds as a promising functionalization strategy in the development of biomimetic matrices for tissue engineering. A totally new approach for scaffold functionalization with peptides is based on Molecular Imprinting technology. In this work, imprinted particles with recognition properties toward laminin and fibronectin bioactive moieties were synthetized and used for the functionalization of biomimetic sponges, which were based on a blend of alginate, gelatin, and elastin. Functionalized sponges underwent a complete morphological, physicochemical, mechanical, functional, and biological characterization. Micrographs of functionalized sponges showed a highly porous structure and a quite homogeneous distribution of imprinted particles on their surface. Infrared and thermal analyses pointed out the presence of interactions between blend components. Biodegradation and mechanical properties appeared adequate for the aimed application. The results of recognition tests showed that the deposition on sponges did not alter the specific recognition and binding behavior of imprinted particles. In vitro biological characterization with cardiac progenitor cells showed that early cell adherence was promoted. In vivo analysis showed that developed scaffolds improved cardiac progenitor cell adhesion and differentiation toward myocardial phenotypes.
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http://dx.doi.org/10.3390/biomimetics5040067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768388PMC
December 2020

Adaptation to ionizing radiation of higher plants: From environmental radioactivity to chernobyl disaster.

J Environ Radioact 2020 Oct 10;222:106375. Epub 2020 Aug 10.

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy. Electronic address:

The purpose of this work is to highlight the effects of ionizing radiation on the genetic material in higher plants by assessing both adaptive processes as well as the evolution of plant species. The effects that the ionizing radiation has on greenery following a nuclear accident, was examined by taking the Chernobyl Nuclear Power Plant disaster as a case study. The genetic and evolutionary effects that ionizing radiation had on plants after the Chernobyl accident were highlighted. The response of biota to Chernobyl irradiation was a complex interaction among radiation dose, dose rate, temporal and spatial variation, varying radiation sensitivities of the different plants' species, and indirect effects from other events. Ionizing radiation causes water radiolysis, generating highly reactive oxygen species (ROS). ROS induce the rapid activation of detoxifying enzymes. DeoxyriboNucleic Acid (DNA) is the object of an attack by both, the hydroxyl ions and the radiation itself, thus triggering a mechanism both direct and indirect. The effects on DNA are harmful to the organism and the long-term development of the species. Dose-dependent aberrations in chromosomes are often observed after irradiation. Although multiple DNA repair mechanisms exist, double-strand breaks (DSBs or DNA-DSBs) are often subject to errors. Plants DSBs repair mechanisms mainly involve homologous and non-homologous dependent systems, the latter especially causing a loss of genetic information. Repeated ionizing radiation (acute or chronic) ensures that plants adapt, demonstrating radioresistance. An adaptive response has been suggested for this phenomenon. As a result, ionizing radiation influences the genetic structure, especially during chronic irradiation, reducing genetic variability. This reduction may be associated with the fact that particular plant species are more subject to chronic stress, confirming the adaptive theory. Therefore, the genomic effects of ionizing radiation demonstrate their likely involvement in the evolution of plant species.
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http://dx.doi.org/10.1016/j.jenvrad.2020.106375DOI Listing
October 2020

IGF-1 loaded injectable microspheres for potential repair of the infarcted myocardium.

J Biomater Appl 2021 02 9;35(7):762-775. Epub 2020 Aug 9.

Department of Medicine and Surgery, University of Parma, Parma, Italy.

The use of injectable scaffolds to repair the infarcted heart is receiving great interest. Thermosensitive polymers, polymerization, cross-linking, and self-assembling peptides are the most investigated approaches to obtain injectability.Aim of the present work was the preparation and characterization of a novel bioactive scaffold, in form of injectable microspheres, for cardiac repair. Gellan/gelatin microspheres were prepared by a water-in-oil emulsion and loaded by adsorption with Insulin-like growth factor 1 to promote tissue regeneration. Obtained microspheres underwent morphological, physicochemical and biological characterization, including cell culture tests in static and dynamic conditions and tests. Morphological analysis of the microspheres showed a spherical shape, a microporous surface and an average diameter of 66 ± 17µm (under dry conditions) and 123 ± 24 µm (under wet conditions). Chemical Imaging analysis pointed out a homogeneous distribution of gellan, gelatin and Insulin-like growth factor-1 within the microsphere matrix. cell culture tests showed that the microspheres promoted rat cardiac progenitor cells adhesion, and cluster formation. After dynamic suspension culture within an impeller-free bioreactor, cells still adhered to microspheres, spreading their cytoplasm over microsphere surface. Intramyocardial administration of microspheres in a cryoinjury rat model attenuated chamber dilatation, myocardial damage and fibrosis and improved cell homing.Overall, the findings of this study confirm that the produced microspheres display morphological, physicochemical, functional and biological properties potentially adequate for future applications as injectable scaffold for cardiac tissue engineering.
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http://dx.doi.org/10.1177/0885328220948501DOI Listing
February 2021

Development and characterization of a suturable biomimetic patch for cardiac applications.

J Mater Sci Mater Med 2019 Nov 14;30(11):126. Epub 2019 Nov 14.

Department of Civil and Industrial Engineering (DICI), University of Pisa, Largo Lucio Lazzarino, 56126, Pisa, Italy.

3D scaffolds used to repair damaged tissues should be able to mimic both composition and functions of natural extracellular matrix, which is mainly composed of polysaccharides and proteins. In our previous research new biomimetic sponges, based on blends of alginate with gelatin, were produced and characterized for myocardial tissue engineering applications. It was observed that these scaffolds can potentially function as a promising cardiac extracellular matrix substitute, but a reinforcement is required to improve their suturing properties. Aim of the present work was the development of a suturable biomimetic patch by the inclusion of a synthetic mesh within an alginate/gelatin scaffold. The mesh, produced by dry spinning, was made of eight superimposed layers of polycaprolactone microfibers, each one rotated of 45° with respect to the adjacent one. Reinforced scaffolds were obtained through the use of a mold, specially designed to place the fibrous mesh exactly in the center of the sponge. Both the reinforcement mesh and the reinforced scaffold were characterized. A perfect integration between the mesh and the sponge was observed. The fibrous mesh reduced the capacity of the sponge to absorb water, but the degree of hydrophilicity of the material was still comparable with that of natural cardiac tissue. The reinforced system showed a suitable stability in aqueous environment and it resulted much more resistant to suturing than not reinforced scaffold and even than human arteries. Polycaprolactone mesh was not cytotoxic and the reinforced scaffold was able to support cardiomyocytes adhesion and proliferation. Overall, the obtained results confirmed that the choice to modify the alginate/gelatin sponges through the insertion of an appropriate reinforcement system turned out to be correct in view of their potential use in myocardial tissue engineering.
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http://dx.doi.org/10.1007/s10856-019-6327-6DOI Listing
November 2019

Influence of injectable microparticle size on cardiac progenitor cell response.

J Appl Biomater Funct Mater 2018 Oct 5;16(4):241-251. Epub 2018 Jul 5.

2 Department of Medicine and Surgery, University of Parma, Parma, Italy.

Introduction: Injectable scaffolds are emerging as a promising strategy in the field of myocardial tissue engineering. Among injectable scaffolds, microparticles have been poorly investigated. The goal of this study was the development of novel gelatin/gellan microparticles that could be used as an injectable scaffold to repair the infarcted myocardium. In particular, the effect of particle size on cardiac progenitor cell response was investigated.

Methods: Particles were produced by a water-in-oil emulsion method. Phosphatidylcholine was used as a surfactant. Particles with different diameter ranges (125-300 µm and 350-450 µm) were fabricated using two different surfactant concentrations. Morphological, physicochemical, and functional characterizations were carried out. Cardiac progenitor cell adhesion and growth on microparticles were tested both in static and dynamic suspension culture conditions.

Results: Morphological analysis of the produced particles showed a spherical shape and porous surface. The hydrophilicity of particle matrix and the presence of intermolecular interactions between gellan and gelatin were pointed out by the physicochemical characterization. A weight loss of 75 ± 5 % after 90 days of hydrolytic degradation was observed. Injectability through a narrow needle (26 G) and persistence of the microparticles at the injection site were preliminarily verified by ex vivo test. In vitro cell culture tests showed a preservation of rat cardiac progenitor biologic properties and indicated a preferential cell adherence to microparticles with a smaller size.

Conclusion: Overall, the obtained results indicate that the produced gelatin/gellan microparticles could be potentially employed as injectable scaffolds for myocardial regeneration.
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http://dx.doi.org/10.1177/2280800018782844DOI Listing
October 2018

Protein/polysaccharide-based scaffolds mimicking native extracellular matrix for cardiac tissue engineering applications.

J Biomed Mater Res A 2018 03 20;106(3):769-781. Epub 2017 Nov 20.

Department of Civil and Industrial Engineering, University of Pisa, Largo Lucio Lazzarino, Pisa, 56126, Italy.

Tissue engineering has emerged as a viable approach to treat disease or repair damage in tissues and organs. One of the key elements for the success of tissue engineering is the use of a scaffold serving as artificial extracellular matrix (ECM). The ECM hosts the cells and improves their survival, proliferation, and differentiation, enabling the formation of new tissue. Here, we propose the development of a class of protein/polysaccharide-based porous scaffolds for use as ECM substitutes in cardiac tissue engineering. Scaffolds based on blends of a protein component, collagen or gelatin, with a polysaccharide component, alginate, were produced by freeze-drying and subsequent ionic and chemical crosslinking. Their morphological, physicochemical, and mechanical properties were determined and compared with those of natural porcine myocardium. We demonstrated that our scaffolds possessed highly porous and interconnected structures, and the chemical homogeneity of the natural ECM was well reproduced in both types of scaffolds. Furthermore, the alginate/gelatin (AG) scaffolds better mimicked the native tissue in terms of interactions between components and protein secondary structure, and in terms of swelling behavior. The AG scaffolds also showed superior mechanical properties for the desired application and supported better adhesion, growth, and differentiation of myoblasts under static conditions. The AG scaffolds were subsequently used for culturing neonatal rat cardiomyocytes, where high viability of the resulting cardiac constructs was observed under dynamic flow culture in a microfluidic bioreactor. We therefore propose our protein/polysaccharide scaffolds as a viable ECM substitute for applications in cardiac tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 769-781, 2018.
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http://dx.doi.org/10.1002/jbm.a.36272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845858PMC
March 2018

Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review.

J R Soc Interface 2015 Jul;12(108):20150254

The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.
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http://dx.doi.org/10.1098/rsif.2015.0254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528590PMC
July 2015

Gelatin/PLLA sponge-like scaffolds allow proliferation and osteogenic differentiation of human mesenchymal stromal cells.

Macromol Biosci 2008 Sep;8(9):819-26

Department of Human Morphology and Applied Biology, Section of Histology and General Embryology, University of Pisa, 56126 Pisa, Italy.

Tissue engineering has the potential to supply constructs capable of restoring the normal function of native tissue following injury. Poly(L-lactic acid) (PLLA) scaffolds are amongst the most commonly used biodegradable polymers in tissue engineering and previous studies performed on ovine fibroblasts have showed that addition of gelatin creates a favorable hydrophilic microenvironment for the growth of these cells. The attractiveness of using mesenchymal stromal cells (MSCs) in tissue regeneration is that they are able to differentiate into several lines including osteoblasts. In this study, we investigated the ability of gelatin/PLLA sponges to support the adhesion, proliferation, and osteogenic differentiation of human MSCs isolated from the bone marrow of four donors. [Figure: see text].
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http://dx.doi.org/10.1002/mabi.200700331DOI Listing
September 2008

Urease loaded alginate microspheres for blood purification.

J Microencapsul 2008 Dec;25(8):569-76

CRIM Lab, Center for Research In Microengineering, Scuola Superiore Sant'Anna, Viale Rinaldo Piaggio, 34-56025 Pontedera (PI), Italy.

In this paper a device, based on urease-loaded microspheres, is presented. The first task of this work was the optimization of a procedure for the alginate microspheres realization, having a radius as close as possible to the optimal one necessary to achieve the maximum enzyme exploitation. This optimal radius was calculated theoretically through a mathematical model which describes the concentration of substrate (urea) inside the microspheres on the assumption of a diffusion-reaction mechanism. The enzyme-loaded microspheres were successfully tested in a prototypal device aimed at the depletion of urea from a circulating fluid simulating blood flow: the results showed that urea concentration in the circulating fluid drops down to less than 25% of the initial value after 5 h.
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http://dx.doi.org/10.1080/02652040802081227DOI Listing
December 2008

Interaction of human gingival fibroblasts with PVA/gelatine sponges.

Micron 2008 Jul 10;39(5):569-79. Epub 2007 Jul 10.

Department of Human Morphology and Applied Biology, Medical Histology and Embriology Section, Faculty of Medicine, University of Pisa, Italy.

Tissue engineering scaffolds should be able to reproduce optimal microenvironments in order to support cell attachment, three-dimensional growth, migration and, regarding fibroblasts, must also promote extracellular matrix production. Various bioactive molecules are employed in the preparation of spongy scaffolds to obtain biomimetic matrices by either surface-coating or introducing them into the bulk composition of the biomaterial. The biomimetic properties of a spongy matrix composed of PVA combined with the natural component gelatine were evaluated by culturing human gingival fibroblasts on the scaffold. Cell adhesion, morphology and distribution within the scaffold were assessed by histology and electron microscopy; viability and metabolic activity as well as extracellular matrix production were analyzed by MTT assay, cytochemistry and immunocytochemistry. Fibroblasts interacted positively with PVA/gelatine. They adhered to the PVA/gelatine matrix in which they had good spreading activity and active metabolism; fibroblasts were also able to produce extracellular matrix molecules (type I collagen, fibronectin and laminin) compared to bi-dimensionally grown cells. The in situ creation of a biological matrix by human fibroblasts together with the ability to produce growth factor TGF-beta1 and the intracellular signal transduction molecule RhoA, suggests that this kind of PVA/gelatine sponge may represent a suitable support for in vitro extracellular matrix production and connective tissue regeneration.
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http://dx.doi.org/10.1016/j.micron.2007.06.016DOI Listing
July 2008

Gelatine/PLLA sponge-like scaffolds: morphological and biological characterization.

J Mater Sci Mater Med 2007 Jul 3;18(7):1399-405. Epub 2007 Feb 3.

Department of Chemical Engineering, University of Pisa, Via Diotisalvi 2, 56126 Pisa, Italy.

Biodegradable synthetic polymers such as poly(lactic acid) (PLA) are widely used to prepare scaffolds for cell transplantation and tissue growth, using different techniques set up for the purpose. However the poor hydrophilicity of these polymers represents the main limitation to their use as scaffolds because it causes a low affinity for the cells. An effective way to solve this problem could be represented by the addition of biopolymers that are in general highly hydrophilic. The present work concerns porous biodegradable sponge-like systems based on poly(L-lactic acid) (PLLA) and gelatine. Morphology and porosity characteristics of the sponges were studied by scanning electron microscopy and mercury intrusion porosimetry respectively. Blood compatibility was investigated by bovine plasma fibrinogen (BPF) adsorption test and platelet adhesion test (PAT). The cell culture method was used in order to evaluate the ability of the matrices to work as scaffolds for tissue regeneration. The obtained results indicate that the sponges have interesting porous characteristics, good blood compatibility and above all good ability to support cell adhesion and growth. In fact viable and metabolically active animal cells were found inside the sponges after 8 weeks in culture. On this basis the systems produced seem to be good candidates as scaffolds for tissue regeneration.
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http://dx.doi.org/10.1007/s10856-007-0127-0DOI Listing
July 2007

Gelatine/PLLA sponge-like scaffolds: morphological and biological characterization.

J Mater Sci Mater Med 2006 Dec;17(12):1211-7

Department of Chemical Engineering, University of Pisa, Via Diotisalvi 2, 56126 Pisa, Italy.

Biodegradable synthetic polymers such as poly(lactic acid) are widely used to prepare scaffolds for cell transplantation and tissue growth, using different techniques set up for the purpose. However the poor hydrophilicity of these polymers represents the main limitation to their use as scaffolds because it causes a low affinity for the cells. An effective way to solve this problem could be represented by the addition of biopolymers that are in general highly hydrophilic. The present work concerns porous biodegradable sponge-like systems based on poly(L-lactic acid) and gelatine. Morphology and porosity characteristics of the sponges were studied by scanning electron microscopy and mercury intrusion porosimetry respectively. Blood compatibility was investigated by bovine plasma fibrinogen adsorption test and platelet adhesion test. The cell culture method was used in order to evaluate the ability of the matrices to work as scaffolds for tissue regeneration. The obtained results indicate that the sponges have interesting porous characteristics, good blood compatibility and above all good ability to support cell adhesion and growth. In fact viable and metabolically active animal cells were found inside the sponges after 8 weeks in culture. On this basis the systems produced seem to be good candidates as scaffolds for tissue regeneration.
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http://dx.doi.org/10.1007/s10856-006-0594-8DOI Listing
December 2006

Morphological evaluation of bioartificial hydrogels as potential tissue engineering scaffolds.

J Mater Sci Mater Med 2004 Dec;15(12):1309-13

Department of Chemical Engineering, University of Pisa, Via Diotisalvi 2, 56126, Pisa, Italy.

Poly(vinyl alcohol) hydrogels prepared by freeze-thawing procedure represent synthetic systems widely investigated as non-biodegradable scaffolds for tissue regeneration. In order to improve the biocompatibility properties of pure poly(vinyl alcohol) (PVA) hydrogels, blends of PVA with different biological macromolecules, such hyaluronic acid, dextran, and gelatin were prepared and used to produce "bioartificial hydrogels". The porosity characteristics of these hydrogels were investigated by scanning electron microscopy and mercury intrusion porosimetry. The morphology of bioartificial hydrogels was evaluated and compared with that of pure PVA hydrogels. In particular the effect exerted by each biological component on pore size and distribution was investigated. The obtained results indicate that when a natural macromolecule is added to PVA the internal structure of the material changes. A small amount of biopolymer induces the structural elements of PVA matrix to take on a well evident lamellar appearance and an apparent preferential orientation. Comparing the results of SEM and mercury intrusion porosimetry it was concluded that hydrogels containing 20% of biological component have the most regular structure and at the same time the lowest total porosity. On the contrary samples with the highest content of natural polymer (40%) show the less regular structure and the highest total porosity.
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http://dx.doi.org/10.1007/s10856-004-5739-zDOI Listing
December 2004

Release of dexamethasone from PLGA nanoparticles entrapped into dextran/poly(vinyl alcohol) hydrogels.

J Mater Sci Mater Med 2002 Mar;13(3):265-9

Department of Chemical Engineering, University of Pisa, Via Diotisalvi 2, 56126 Pisa, Italy.

Hydrogels based on blends of poly(vinyl alcohol) (PVA) with dextran were prepared by a physical cross-linking procedure and used as matrices for the entrapment of biodegradable nanoparticles loaded with dexamethasone. The nanoparticles were prepared, by a solvent evaporation technique, using biodegradable copolymers of poly(lactic acid)-poly(glycolic acid) (PLGA). Size, morphology and surface characteristics of the nanoparticles were evaluated by scanning electron microscopy. The mechanism of drug release from the nanoparticles entrapped into the PVA-based matrices was studied and compared to that from free nanoparticles. The effect of dextran on the in vitro release profile of dexamethasone from the hydrogels was investigated. The obtained results indicate that PLGA nanoparticles are able to release dexamethasone following a diffusion-controlled mechanism. The entrapment of the nanoparticles into the hydrogels affects only slightly this mechanism of drug release. In addition, dextran/PVA hydrogels release a higher amount of drug with respect to pure PVA hydrogels and by increasing dextran content in the hydrogels, the amount of drug released increases.
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http://dx.doi.org/10.1023/a:1014006800514DOI Listing
March 2002

Gelatin nanoparticles produced by a simple W/O emulsion as delivery system for methotrexate.

J Mater Sci Mater Med 2002 May;13(5):523-6

Department of Chemical Engineering, University of Pisa, Via Diotisalvi 2, 56126 Pisa, Italy.

Biodegradable hydrophilic gelatin nanoparticles, containing different initial amounts of methotrexate (MTX), were prepared using a simple solvent evaporation technique based on a single water-in-oil emulsion and stabilized by the use of glutaraldehyde as cross-linking agent. The effects of several parameters on particle size, drug encapsulation efficiency and drug release were investigated. Size and shape of the nanoparticles were examined by scanning electron microscopy. The release of MTX was monitored in vitro and the mechanism of release was studied. Particles with a mean diameter of 100-200 nm were produced, which were able to release MTX following a diffusion-controlled mechanism of release. It was observed that the initial amount of MTX used for sample loading did not have any effect on the pattern of release, while it affected the amount of drug entrapped into the nanoparticles and also both the release rate and the total amount of drug released.
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http://dx.doi.org/10.1023/a:1014791327253DOI Listing
May 2002

Poly(vinyl alcohol) hydrogels as hydrophilic matrices for the release of lipophilic drugs loaded in PLGA nanoparticles.

J Mater Sci Mater Med 2002 Jan;13(1):29-32

Department of Chemical Engineering, University of Pisa, Via Diotisalvi 2, 56126 Pisa, Italy.

Poly(vinyl alcohol) (PVA) hydrogels prepared by a freeze-thawing procedure were evaluated as matrices for the release of water-insoluble drugs such as dexamethasone. As it is impossible to directly entrap a lipophilic drug into a hydrophilic matrix, a novel mechanism has been designed based on producing biodegradable nanoparticles loaded with the drug, that could then be entrapped into the hydrogels. Nanoparticles were prepared by a solvent evaporation technique using a biodegradable copolymer of poly(lactic acid)-poly(glycolic acid) (PLGA). The effects of several processing parameters on particle properties were investigated. The drug release from free nanoparticles was compared to that from the nanoparticles entrapped into the PVA matrices. It was observed that the release profile of the drug is not significantly affected by the PVA matrix. A correlation was found between the amount of drug released and the PVA concentration in the hydrogels: the percentage of drug released, as a function of time, decreased by increasing PVA concentration, indicating that PVA concentration can be used as a tool in modulating the release of the drug.
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http://dx.doi.org/10.1023/a:1013674200141DOI Listing
January 2002
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