Costas Demetzos

National and Kapodistrian University of Athens, Athínai, Attica, Greece

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Publications (154)321.76 Total impact

  • International Journal of Pharmaceutics. 10/2014; 473(s 1–2):80–86.
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    ABSTRACT: Abstract Liposomes are widely used as delivery systems of cytotoxic drugs. The encapsulation into liposomes improves pharmacological properties and as a result therapeutic index and outcomes. To date, liposomal vincristine and cytarabine are approved and marketed for intravenous and intrathecal administration, respectively. The main goal of this review is to examine the clinical use and pharmacological properties, as well as the safety of liposomal forms of less widely used liposomal forms of anticancer agents compared to their conventional forms and to present data regarding clinical development of other liposomal agents. Liposomal forms of cytarabine and vincristine are less widely used and unknown compared to liposomal anthracyclines, because they are approved only for specific indications and only in the United States.
    Journal of Liposome Research 08/2014; · 1.91 Impact Factor
  • Costas Demetzos, Natassa Pippa
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    ABSTRACT: The morphology of drug nanocarriers correlates with their functionality, which is mainly shuttled on their surface where most of the interactions and interfacial phenomena occur. The quantification of their morphological fingerprint requires an analytical tool that should be established based on experimental data and can be correlated with their stability. The morphological quantification picture of the advanced Drug Delivery nano Systems (aDDnSs) could be achieved via fractal analysis and by introducing a novel proposed parameter, defined as ωD. This parameter is based on mathematical limits determined experimentally and on already existing theories on the colloidal fractal aggregation process which can correlate the morphological characteristics of aDDnSs with their physicochemical stability in aqueous and biological media. This review article proposes the fractal analysis and the ωD as an analytical tool and prediction parameter, respectively, which are able to promote an attractive and alternative path for studying drug delivery nanocarriers. Moreover, these approaches could facilitate the scale up process of pharmaceutical industry, and could shed more light in the quantification of drug delivery nanosystems.
    International Journal of Pharmaceutics 07/2014; · 3.99 Impact Factor
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    ABSTRACT: The aim of this work is to design and develop a suitable polymeric formulation incorporating amphotericin B (Ampho B) in order to overcome its water insolubility problem. To this end, we have chosen the poly(isoprene-b-ethylene oxide) amphiphilic block copolymer (IEO) family. We investigate the self assembly behavior and the stability kinetics of IEO copolymer based nanostructures formed in HPLC grade water and in phosphate buffer saline (PBS). The IEO block copolymer samples investigated have different molecular weights and compositions. A gamut of light scattering techniques (static, dynamic and electrophoretic) were used in order to extract information on the size, ζ-potential and morphological characteristics of the structures formed, as a function of the molar ratio of incorporated lipophilic drug Ampho B. The amphiphilic character and the colloidal stability of the particular polymeric drug vectors indicate that these nanostructures can be utilized as effective containers for the particular hydrophobic drug. The incorporation of Ampho B led to alteration of the physicochemical and morphological characteristics of the pure polymeric carriers. It is observed that the in vitro release of Ampho B from the prepared vectors IEO-b:Ampho B was quite slow, while the IEO-a carriers did not release Ampho B.
    International journal of pharmaceutics. 07/2014;
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    ABSTRACT: Terbinafine hydrochloride (TBH) (E)-N-(6,6-dimethyl-2-hepten-4-inyl)-N-methyl-1-naphthaline-methanamine(-hydrochloride) is an effective antifungal agent already existing on the market in the form of topical formulations. The present study deals with the preparation and physicochemical characterization (size, polydispersity, zeta-potential) of 1,2-Diacyl-sn-glycero-3-phosphocholine (EggPC) incorporating TBH in two different dispersion media (tris-buffered saline (TBS) of pH 7.4 or in phosphate buffer solution (PS) of pH 5.5) in order to investigate how pH of dispersion media affects the incorporation efficiency of TBH into liposomes. There were further prepared three Carbopol 934 hydrogels of different concentrations (0.5, 1 and 2%) and their viscosity was measured and evaluated. Moreover, the in vitro drug release from three liposomal gels was studied, in order to investigate the ability of liposomes to act as carriers for TBH in a gel. All formulations were found to retain their original physicochemical properties at least for three weeks. These early studies on the release kinetics from liposomal gel show that Korsmeyer-Peppas model could be the best fitted model concerning the TBH release profile and could be supported biophysically from extended Derjaguin-Landau-Verwey-Overbeek (DLVO) theory.
    Journal of Nanoscience and Nanotechnology 06/2014; 14(6):4529-33. · 1.15 Impact Factor
  • Natassa Pippa, Stergios Pispas, Costas Demetzos
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    ABSTRACT: Abstract The major advance of mixed liposomes (the so-called chimeric systems) is to control the size, structure, and morphology of these nanoassemblies, and therefore, system colloidal properties, with the aid of a large variety of parameters, such as chemical architecture and composition. The goal of this study is to investigate the alterations of the physicochemical and morphological characteristics of chimeric dipalmitoylphosphatidylcholine (DPPC) liposomes, caused by the incorporation of block and gradient copolymers (different macromolecular architecture) with different chemical compositions (different amounts of hydrophobic component). Light scattering techniques were utilized in order to characterize physicochemically and to delineate the fractal morphology of chimeric liposomes. In this study, we also investigated the structural differences between the prepared chimeric liposomes as are visualized by scanning electron microscopy (SEM). It could be concluded that all the chimeric liposomes have regular structure, as SEM images revealed, while their fractal dimensionality was found to be dependent on the macromolecular architecture of the polymeric guest.
    Journal of Liposome Research 03/2014; · 1.91 Impact Factor
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    ABSTRACT: The purposes of this study were to investigate the indomethacin (IND) release profile from Dipalmytolphosphatidylcholine: Poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline) (DPPC:MPOx) (in different molar ratios) mixed liposomal nanovectors, to examine the relevance of power law using these experimental release data, and to detect the relationship of the fractal dimension (df) of nanovectors with the fraction of the IND release. The df of the mixed liposomes was determined by Static Light Scattering during the release of IND from the nanocontainers. It is observed that the in vitro release of the drug from the prepared nanostructures is quite fast especially for the nanovectors prepared with the lower ratio of MPOx. The release kinetics was studied by regression analysis of drug concentrations in fractal matrices with respect to time. A power law, a piece-wise power law functions and Weibull distribution were fitted to the release data and the model parameters were estimated. Good fits were observed in all datasets analyzed, while distinct regions of different release rates corresponding to different df values were described. The authors proposed that the fractal morphology of the mixed liposomes affects the drug release and must be taken into account to develop liposomal drug with complete knowledge of their structural properties.
    International Journal of Pharmaceutics 02/2014; · 3.99 Impact Factor
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    ABSTRACT: We report on the self assembly behavior and on stability studies of poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline) (MPOx) gradient copolymer nanostructures formed in Phosphate Buffer Saline (PBS). The MPOx gradient copolymer samples investigated (denoted as -a, -b, and -c) have different molecular characteristics. A gamut of light scattering techniques (static, dynamic and electrophoretic) were used in order to extract information on the size and morphological characteristics of the nanoassemblies formed, as a function of gradient copolymer characteristics. The amphiphilic character and the colloidal stability of the particular nanovectors indicate that these nanostructures can be utilized as effective nanocontainers for hydrophobic drugs. The incorporation of indomethacin (IND) led to a decreased size of MPOx-a and MPOx-b nanovectors. It is observed that the in vitro release of IND from the prepared nanovectors MPOx-c:IND (9:1 and 9:2 molar ratio) is quite slow, while the MPOx-a and MPOx-b nanocarriers released IND immediately.
    Advanced Science. 01/2014; 6(6).
  • Costas Demetzos, Natassa Pippa
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    ABSTRACT: Abstract Significant progress has been made in nanoscale drugs and delivery systems employing diverse chemical formulations to facilitate the rate of drug delivery and to improve its pharmacokinetics. Biocompatible nanomaterials have been used as biological markers, contrast agents for imaging, healthcare products, pharmaceuticals, drug-delivery systems as well as in detection, diagnosis and treatment of various types of diseases. The classification of drug delivery nanosystems (DDnSs) is a crucial issue and fundamental efforts on this subject are missing from the literature. This article deals with the classification of DDnSs with a modulatory controlled release profile (MCR) denoted as modulatory controlled release nanosystems (MCRnSs). Conventional (c) and advanced (a) DDnSs are denoted by the acronyms cDDnSs and aDDnSs, and can be composed of a single or more than one biomaterials, respectively. The classification was based on their characteristics such as: surface functionality (f), the nature of biomaterials used and the kind of interactions between biomaterials. The aDDnSs can be classified as hybridic (Hy-) or chimeric (Chi-) based on the nature - same or different respectively - of biomaterials and inorganic materials used. The nature of the elements used for producing advanced biomaterials is of great importance and medicinal chemistry contributes effectively to the production of aDDnSs.
    Drug Delivery 10/2013; · 2.02 Impact Factor
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    ABSTRACT: In this work, tigapotide (PCK3145) was incorporated into novel nanocarriers based on polymeric, lipidic, and dendrimeric components, in order to maximize the advantages of the drug delivery process and possibly its biological properties. PCK3145 was incorporated into lipidic nanocarriers composed of Egg phosphatidylcholine (EggPC) and dipalmytoylphosphatidylcholine (DPPC) (EggPC:PCK3145 and DPPC:PCK3145, 9:0.2 molar ratio), into cationic liposomes composed of EggPC:SA:PCK3145 and DPPC:SA:PCK3145 (9:1:0.2 molar ratio) into complexes with the block polyelectrolyte (quaternized poly[3,5-bis(dimethylaminomethylene)hydroxystyrene]-b-poly(ethylene oxide) (QNPHOSEO) and finally into dendrimeric structures (i.e., PAMAM G4). Light scattering techniques are used in order to examine the size, the size distribution and the Z-potential of the nanocarriers in aqueous and biological media. Fluorescence spectroscopy was utilized in an attempt to extract information on the internal nanostructure and microenvironment of polyelectrolyte/PCK3145 aggregates. Therefore, these studies could be a rational roadmap for producing various effective nanocarriers in order to ameliorate the pharmacokinetic behavior and safety issues of antitumor and anticancer biomolecules.
    Journal of Nanoparticle Research 10/2013; 15(11). · 2.18 Impact Factor
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    ABSTRACT: Fractals have been very successful in quantifying nature's geometrical complexity, and have captured the imagination of scientific community. The development of fractal dimension and its applications have produced significant results across a wide variety of biomedical applications. This review deals with the application of fractals in pharmaceutical sciences and attempts to account the most important developments in the fields of pharmaceutical technology, especially of advanced Drug Delivery nano Systems and of biopharmaceutics and pharmacokinetics. Additionally, fractal kinetics, which has been applied to enzyme kinetics, drug metabolism and absorption, pharmacokinetics and pharmacodynamics are presented. This review also considers the potential benefits of using fractal analysis along with considerations of nonlinearity, scaling, and chaos as calibration tools to obtain information and more realistic description on different parts of pharmaceutical sciences. As a conclusion, the purpose of the present work is to highlight the presence e of fractal geometry in almost all fields of pharmaceutical research.
    International Journal of Pharmaceutics 09/2013; · 3.99 Impact Factor
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    ABSTRACT: PURPOSE: Fractal analysis was used as a tool in order to study the morphological characteristics of PEGylated liposomes. We report on the morphological characteristics of stealth liposomes composed of DPPC and DPPE-PEG 3000 in two dispersion media using fractal analysis. METHODS: Light scattering techniques were used in order to elucidate the size, the morphology and the surface charge of PEGylated liposomes as a function of PEGylated lipid concentration and temperature. Fluorescence spectroscopy studies revealed a microenvironment of low polarity inside the liposomal membranes. RESULTS: All formulations were found to retain their physicochemical characteristics for at least 3 weeks. The hydrodynamic radii (Rh) of stealth liposomes were stable in the process of heating up to 50°C; while the fractal dimension values (df) which correspond to their morphology, have been changed during heating. Hence, these results are a first indication of the presence of a heterogeneous microdomain structure of the stealth liposomal system. The amphiphilic drug indomethacin (IND) was successfully encapsulated within the liposomes and led to an increased size of stealth liposomes, while the morphology of liposomal vectors changed significantly at the highest molar ratio of PEGylated lipid. CONCLUSIONS: We can state that this approach can promote a new analytical concept based on the morphological characteristics and quantify the shape of drug carriers complementary to that of the conventional analytical techniques.
    Pharmaceutical Research 06/2013; · 4.74 Impact Factor
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    ABSTRACT: The combination of natural and synthetic biomaterials leads to the formation of advanced Drug Delivery nano Systems (aDDnSs). The aDDnSs can be classified as hybridic (hy‐) or chimeric (chi‐) based on the nature – same or different respectively ‐ of biomaterials used. Such advanced bio complexes can alter the pharmacokinetic properties of the encapsulated drug and consequently its effectiveness. Numerous studies regarding the usage of natural or synthetic biomaterials as drug carriers have been performed, while only few studies concerning the combination of different kinds of biomaterials have been published. Carriers produced by the combination of liposomes and dendrimers were recently characterized as chi‐aDDnSs belonging to the class of Modulatory Liposomal Controlled Released Systems (MLCRSs) where the polymeric or the dendritic component act as modulator of the drug's release from the carrier. A small but significant number of studies have begun to shed light on the interactions between the components of the bio complexes that seem to be of utmost importance for the pharmacological effectiveness of the final formulation. This review deals with the categorization of the aDDnSs, the nature of the interacting forces between them and their potential biomedical applications.
    05/2013: pages 30-39; , ISBN: 978-1-84973-611-4
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    ABSTRACT: Chimeric advanced Drug Delivery nano Systems (chi-aDDnSs) could be defined as mixed nanosystems composed of different biomaterials that can be organized into new nanostructures that can offer advantages as drug carriers. In this work, we report on the self assembly behavior and on stability studies of chi-aDDnSs consisting of DPPC (dipalmitoylphosphatidylcholine) and poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline) (MPOx) gradient copolymer in Phosphate Buffer Saline (PBS). Light scattering techniques were used in order to extract information on their physicochemical and structural characteristics (i.e. ζ-potential, Polydispersity Index (PD.I.), size/shape and morphology), while their stability was also studied as a function of gradient block copolymer content, as well as temperature. The colloidal stability of the chimeric nanovectors and their thermoresponsive behavior indicates that these nanosystems could be considered as sterically stabilized nanocontainers. DPPC:MPOx chimeric advanced drug delivery nanosystems were found to be effective nanocontainers for the incorporation of indomethacin (IND). The combination of gradient block copolymers with phospholipids for the development of novel chimeric nanovectors is reported for the first time and appears very promising, mostly due to the fact that the MPOx acts as a modulator for the release rate of the IND.
    International Journal of Pharmaceutics 04/2013; · 3.99 Impact Factor
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    ABSTRACT: In this work, we report on the self assembly behavior and stability studies of mixed amphiphilic nanosystems consisting of DPPC (dipalmitoylphosphatidylcholine) and poly(ethylene oxide)-b-poly(ε-caprolactone) (PEO-b-PCL) block copolymer in HPLC-grade water, phosphate buffer saline (PBS) and fetal bovine serum (FBS). These nanosystems are sterically stabilized nanovectors and can be utilized as chimeric advanced Drug Delivery nano Systems (aDDnSs) with stealth properties. A gamut of light scattering techniques (static, dynamic and electrophoretic) and fluorescence spectroscopy were used in order to extract information on the structure, morphology, size, effective charge and internal nanostructure of the nanoassemblies formed, as a function of block copolymer content, as well as temperature and concentration. The incorporation of PEO-b-PCL leads to nanoassemblies of smaller size. All the mixed formulations were found to retain their original physicochemical characteristics for the course of two weeks. The hydrodynamic radii (Rh) of mixed nanosystems decreased in the process of heating up to 50 °C. Gradual degradation of the polymeric chain in an acidic dispersion medium, which leads to gradual structural changes of the chimeric nanovectors, was observed. The micropolarity of the hydrocarbon region of nanocarriers changed significantly in HPLC-grade water and PBS with increasing block copolymer content. The incorporation of indomethacin (IND) led to a decreased size of chimeric nanocarriers. The incorporation efficiency of mixed liposomal–block copolymer formulations for IND was increased in PBS in comparison with the HPLC-grade water, due to electrostatic interactions between the drug molecule and choline headgroups. PEO-b-PCL grafted DPPC liposomes are found to be effective nanocontainers for the encapsulation of IND, especially at the highest molar ratio of the block copolymer.
    Soft Matter 03/2013; 9(15):4073-4082. · 4.15 Impact Factor
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    ABSTRACT: Abstract Dimethoxycurcumin (DMC) is a lipophilic analog of curcumin found in Curcuma longa Linn., which is known to possess significant activity against various cancer cell lines. The purpose of this study was to develop suitable liposomal formulations in order to overcome DMC's poor water solubility and to study the aggregation kinetic profile using the fractal analysis. DMC was incorporated into liposomal formulations composed of DPPC, DPPC:DPPG:chol (9:1:1 molar ratio) and DPPC:DODAP:chol (9:1:1 molar ratio) liposomes. Light scattering techniques were used to elucidate the physicochemical parameters of the liposomal formulations with and without DMC. The structural characteristics of the incorporated molecule were found to be crucial and promote the aggregation mechanism depending also on the liposomes' composition. The results of our study contribute to the overall scientific efforts to prepare efficient carriers for DMC and could be a useful tool in order to study more efficiently the kinetics of the aggregation process of the liposomal carriers.
    Journal of Liposome Research 01/2013; · 1.91 Impact Factor
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    ABSTRACT: In this study, we report on the self assembly behavior and on stability studies of mixed (chimeric) nanosystems consisting of dipalmitoylphosphatidylcholine (DPPC) and poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline) (MPOx) gradient copolymer in aqueous media and in fetal bovine serum (FBS). A gamut of light scattering techniques and fluorescence spectroscopy were used in order to extract information on the size and morphological characteristics of the nanoassemblies formed, as a function of gradient block copolymer content, as well as temperature. The hydrodynamic radii (R h) of nanoassemblies decreased in the process of heating up to 50 °C, while the fractal dimension (d f) values, also increased. Indomethacin was successfully incorporated into these chimeric nanocarriers. Drug release was depended on the components ratio. The present studies show that there are a number of parameters that can be used in order to alter the properties of chimeric nanosystems, and this is advantageous to the development of “smart” nanocarriers for drug delivery.
    Journal of Nanoparticle Research 01/2013; 15(6). · 2.18 Impact Factor
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    ABSTRACT: The application of polymers in medicine, as components of drug carriers, as well as their synthetic strategies are considered essential for producing and developing new drug formulations against human deceases. The synthesis of block copolymers is a time-consuming process with a high cost of the final product, although several block copolymer systems have been already commercialized successfully. The biocompatibility, the biodegradability and the non toxic profile of newly synthesized polymers towards healthy tissues, should be taken into account in order to be acceptable for biomedical applications. In this review article, focus is placed on new approaches and synthetic strategies for preparing novel block copolymers and their utilization as parts of new and advanced Drug Delivery nanoSystems (aDDnSs) with a Modulatory Controlled Release profile (MCR). Such complex and advanced nanosystems can alter the pharmacokinetic properties of the encapsulated drug and consequently its effectiveness. Emphasis is given to the use of living polymerization methodologies and post polymerization chemical transformation reactions for the synthesis of mainly diblock copolymers for novel drug delivery nanosystems. Issues related to self-assembly of block copolymers in solution toward formation of colloidal functional nanostructures that can serve as nanocontainers and nanocarriers, and strategies for controlling encapsulation of specific drugs are also discussed. Specific examples are reported mainly on diblock copolymer systems, including authors recent work.
    Current Medicinal Chemistry 09/2012; · 3.72 Impact Factor
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    ABSTRACT: New nano-scale drug carriers offer the possibility of increasing the therapeutic index of drug molecules by increasing their effectiveness, diminishing their toxicity against physiological tissues and achieving controlled therapeutic levels for a prolonged time. This review gives an overview of approaches to the development of these novel complex nanocarriers with emphasis on those involving dendrimers and related systems. The combination of two of more nano-sized units for producing an overall system with unique properties could be advantageous compared to more simple nanotechnology-based carriers. Recent advances in medicinal chemistry offer the possibility of exact tailoring of the properties of such complex systems which, in conjunction with full physicochemical characterization, may lead to novel and highly effective drug products. An assessment is given of the potential of systems such as chimeric advanced Drug Delivery nano Systems (chi-aDDnSs) for the delivery of drugs compared with conventional carriers. Rational synthesis of molecules that can act as modulators of the properties of chi-aDDnSs and may be the future in the design and development of nanocarriers, not only for the delivery of drug molecules but also for genetic material and imaging agents.
    Current Medicinal Chemistry 09/2012; · 3.72 Impact Factor

Publication Stats

1k Citations
321.76 Total Impact Points

Institutions

  • 2002–2014
    • National and Kapodistrian University of Athens
      • • Department of Pharmaceutical Technology
      • • Division of Pharmacology
      Athínai, Attica, Greece
  • 1998–2013
    • Athens State University
      • Department of Chemistry
      Athens, Alabama, United States
  • 2012
    • National Technical University of Athens
      • Τομέας Φυσικής
      Athens, Attiki, Greece
  • 2011
    • University of Lodz
      • Department of General Biophysics
      Łódź, Lodz Voivodeship, Poland
  • 2001–2011
    • Julphar School of Pharmacy
      Greece, New York, United States
  • 2005–2010
    • National Hellenic Research Foundation
      Athínai, Attica, Greece
  • 2008
    • Monash University (Australia)
      • Department of Biochemistry and Molecular Biology
      Melbourne, Victoria, Australia
  • 2007
    • Ecole Pratique des Hautes Etudes
      Lutetia Parisorum, Île-de-France, France
  • 2006–2007
    • Academy of Athens
      Athínai, Attica, Greece
  • 2000
    • International Institute of Anticancer Research
      Αθίκια, Peloponnese, Greece
  • 1990–1994
    • Université René Descartes - Paris 5
      • Faculté des Sciences Pharmaceutiques et Biologiques de Paris
      Paris, Ile-de-France, France