Costas Demetzos

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

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Publications (168)383.28 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Insulin (INS) was incorporated into complexes with the block polyelectrolyte quaternized poly[3,5-bis(dimethylaminomethylene)hydroxystyrene]-b-poly(ethylene oxide) (QNPHOSEO), which is a cationic-neutral block polyelectrolyte. Light scattering techniques are used in order to examine the size, the size distribution and the ζ-potential of the nanocarriers in aqueous and biological media, which are found to depend on the ratio of the components and the physicochemical parameters during and after complex preparation. Circular dichroism and infrared spectroscopy, employed to investigate the structure of the complexed INS, show no alteration of protein structure after complexation. In vitro release profiles of the entrapped protein are found to depend on the ratio of the components and the solution conditions used during preparation of the complexes. Copyright © 2015. Published by Elsevier B.V.
    International Journal of Pharmaceutics 06/2015; DOI:10.1016/j.ijpharm.2015.06.013 · 3.65 Impact Factor
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    ABSTRACT: Insulin (INS) was encapsulated into complexes with poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLys), which is a polypeptide-based block copolymer (a neutral-cationic block polyelectrolyte). The particular cationic-neutral block copolymer can complex INS molecules in aqueous media via electrostatic interactions. Light scattering techniques are used in order to study the complexation process and structure of the hybrid nanoparticles in a series of buffers, as a function of protein concentration. The physicochemical and structural characteristics of the complexes depend on the ionic strength of the aqueous medium, while the concentration of PEG-b-PLys was constant through the series of solutions. As INS concentration increased the size distribution of the complexes decreased, especially at the highest ionic strength. The size/structure of complexes diluted in biological medium indicated that the copolymer imparts stealth properties and colloidal and biological stability to the complexes, features which could in turn affect the clearance properties in vivo. Therefore, these studies could be a rational roadmap for designing the optimum complexes/effective nanocarriers for proteins and peptides.
    The Journal of Physical Chemistry B 05/2015; 119(22). DOI:10.1021/acs.jpcb.5b01664 · 3.30 Impact Factor
  • Costas Demetzos
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    ABSTRACT: Biophysics and thermodynamics are considered as the scientific milestones for investigating the properties of materials. The relationship between the changes of temperature with the biophysical variables of biomaterials is important in the process of the development of drug delivery systems. Biophysics is a challenge sector of physics and should be used complementary with the biochemistry in order to discover new and promising technological platforms (i.e., drug delivery systems) and to disclose the 'silence functionality' of bio-inspired biological and artificial membranes. Thermal analysis and biophysical approaches in pharmaceuticals present reliable and versatile tools for their characterization and for the successful development of pharmaceutical products. The metastable phases of self-assembled nanostructures such as liposomes should be taken into consideration because they represent the thermal events can affect the functionality of advanced drug delivery nano systems. In conclusion, biophysics and thermodynamics are characterized as the building blocks for design and development of bio-inspired drug delivery systems.
    AAPS PharmSciTech 04/2015; 16(3). DOI:10.1208/s12249-015-0321-1 · 1.78 Impact Factor
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    ABSTRACT: Novel polymer-modified thermosensitive liposomes were developed for the delivery of indomethacin in order to control its release profile. When attached to 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes, the end functionalized C12H25-poly(N-isopropylacrylamide)-COOH (C12H25-PNIPAM-COOH) polymer was membrane-disruptive in a temperature-dependent manner. The interest for this polymer is driven by its famous lower critical solution temperature (LCST) behavior, where heating an aqueous solution of PNIPAM above 32°C induces nanophase separation and polymer chain aggregation. The physicochemical/structural behavior of these polymer-modified thermosensitive liposomes was found to depend on the PNIPAM:lipid molar ratio and the composition of the polymeric guest. The incorporation of PNIPAM has caused alterations in the thermotropic behavior of DPPC liposomes, as the differential scanning calorimetry (DSC) experiments revealed. The drug loading and the release were found to be strongly dependent on the thermotropic characteristics of the PNIPAM grafted DPPC liposomes. Namely, the in vitro release is immediate at 37°C (>LCST) ("burst" effect), while the prepared mixed nanocarriers did not release the encapsulated bioactive substance at <32°C (<LCST). Thus the thermosensitivity and the drug loading/release properties of the prepared formulations can be modulated by varying the ratio of DPPC/PNIPAM components, as well as the molecular characteristics of the polymeric guest. Copyright © 2015 Elsevier B.V. All rights reserved.
    International Journal of Pharmaceutics 03/2015; 485(1-2). DOI:10.1016/j.ijpharm.2015.03.014 · 3.65 Impact Factor
  • Costas Demetzos · Natassa Pippa
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    ABSTRACT: Nanosimilars are considered as new medicinal outcomes combining the generic drugs and the nanocarrier as an innovative excipient, in order to evaluate them as final products. They belong to the grey area - concerning the evaluation process - between generic drugs and biosimilar medicinal products. Generic drugs are well documented and a huge number of them are in market, replacing effectively the off-patent drugs. The scientific approach for releasing them to the market is based on bioequivalence studies, which are well documented and accepted by the regulatory agencies. On the other hand, the structural complexity of biological/biotechnology-derived products demands a new approach for the approval process taking into consideration that bioequivalence studies are not considered as sufficient as in generic drugs, and new clinical trials are needed to support their approval process of the product to the market. In proportion, due to technological complexity of nanomedicines, the approaches for proving the statistical identity or the similarity for generic and biosimilar products, respectively, with those of prototypes, are not considered as effective for nanosimilar products. The aim of this note is to propose a complementary approach which can provide realistic evidences concerning the nanosimilarity, based on fractal analysis. This approach is well fit with the structural complexity of nanomedicines and smooths the difficulties for proving the similarity between off-patent and nanosimilar products. Fractal analysis could be considered as the approach that completely characterizes the physicochemical/morphological characteristics of nanosimilar products and could be proposed as a start point for a deep discussion on nanosimilarity. Copyright © 2015 Elsevier B.V. All rights reserved.
    International Journal of Pharmaceutics 02/2015; 483(1-2):1-5. DOI:10.1016/j.ijpharm.2015.02.008 · 3.65 Impact Factor
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    ABSTRACT: Abstract Targeted drug delivery is a method of delivering bioactive compounds to a patient in a manner that increases the therapeutic index. The main goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue. Antibody-drug conjugates (ADC) represent an innovative therapeutic application that combines the unique properties of monoclonal antibodies with the potent cell killing activity of cytotoxic bioactive compounds. ADCs are complex molecules composed of an antibody linked, via a stable, chemical, linker with labile bonds, to a biological active cytotoxic (anticancer) payload or drug. The key components of ADC include a monoclonal antibody, a stable linker and a cytotoxic agent to target a variety of cancers. The present mini-review deals with the examination of clinical use and pharmacological properties, as well as the safety of antibody-drug conjugates that are marketed. Ado-trastuzumab emtasine and brenduximab vedotin were examined regarding their mechanism of action, pharmacology, clinical use and safety. These ADCs selectively deliver cargoes to tumor cells and provide clinical benefit by minimizing systemic toxicity.
    Drug Delivery 01/2015; DOI:10.3109/10717544.2014.998323 · 2.20 Impact Factor
  • Costas Demetzos
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    ABSTRACT: This chapter deals with the classification of Drug Delivery nano Systems (DDnSs) with a Modulatory Controlled Release profile (MCR) denoted as Modulatory Controlled Release nano Systems (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.
    Advances in Experimental Medicine and Biology 01/2015; 822:195-8. DOI:10.1007/978-3-319-08927-0_22 · 2.01 Impact Factor
  • Costas Demetzos
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    ABSTRACT: The purpose of this review is to address the role of the scientific excellence of innovative medicines as the key element in the development process in Greece. The collected statistical information and data on the absorbability of funds for research of innovative medicines, diagnostics, and advanced drug delivery systems pointed out that the Greek scientists could take advantage of the "Horizon 2020" on the continuity of their investigation, whilst how the accumulation of knowledge at Greek universities and research foundations could be translated into industrial products with added value, safe and effective for the European consumers. In conclusion, this review also is considered to provide the potential benefits in order to adapt the signaling of the "Horizon 2020" for the development of a bio-better Europe based on scientific inspirations. This approach could be considered as an interplay between countries and even between the north and west located countries in the European landscape.
    Advances in Experimental Medicine and Biology 01/2015; 822:203-8. DOI:10.1007/978-3-319-08927-0_25 · 2.01 Impact Factor
  • Natassa Pippa · Stergios Pispas · Costas Demetzos
    Advances in Experimental Medicine and Biology 01/2015; 822:199-200. DOI:10.1007/978-3-319-08927-0_23 · 2.01 Impact Factor
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    ABSTRACT: Abstract Liposomes are well-known cell simulators and are currently studied as drug delivery systems, for a targeted delivery of higher drug concentrations, in specific cells. Novel biophotonic techniques for manipulation and characterization of liposomes have been developed; among which are optical tweezers. In our work, we demonstrate a novel use of line optical tweezers to manipulate and cause liposome deformations. Optical forces induce tension on liposomes, which are stretched along the line optical trap. The method of dielectrophoresis, combined with optical tweezers, was used to measure the exerted optical forces. As a consequence, in the case of reversible liposome deformations, the value of the shear and bending moduli of liposomes was calculated. We anticipate that the selective manipulation of liposomes will help us toward a better understanding of the cellular-liposome interactions. Studying the biomechanical properties of liposomes will provide an insight into the mechanical behavior of individual living cells, which have recently been implicated in many aspects of human physiology and patho-physiology. The biomechanical properties of cells (i.e. deformability, stiffness and elasticity) can be useful biomarkers for various disease processes and changes of the cell state.
    Journal of Liposome Research 12/2014; DOI:10.3109/08982104.2014.987784 · 1.53 Impact Factor
  • Natassa Pippa · Maria Mariaki · Stergios Pispas · Costas Demetzos
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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; 22:1-8. DOI:10.3109/08982104.2014.950277 · 1.53 Impact Factor
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    ABSTRACT: Amphiphilic block copolymers and lipids have attracted major scientific interest in recent years due to their intriguing self-assembly behavior, which results in a plethora of nanoassemblies and their potential applications in Pharmaceutical Nanotechnology, as bio-inspired chimeric or hybrid advanced Drug Delivery nano Systems (aDDns). In this work, we report on stability studies of chimeric systems consisted of DPPC (dipalmitoylphosphatidylcholine) and poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) block copolymer in Phosphate Buffer Saline (PBS) and Fetal Bovine Serum (FBS). The incorporation of PEO-b-PCL leads to bio-inspired nanovectors of smaller size, in comparison to DPPC neat liposomes. All the prepared chimeric liposomal formulations were found to retain their original physicochemical characteristics for at least five days. These nanocarriers could be characterized as stealth liposomes due to their biological stability. The composition of the bio-inspired aDDnSs play a key role on their physicochemical and structural properties, as well as on their biological response, which could be a road map for designing aDDnSs based on the bio-inspiration.
    Journal of Nanoscience and Nanotechnology 08/2014; 14(8):5676-5681. DOI:10.1166/jnn.2014.8869 · 1.34 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; 473(1-2). DOI:10.1016/j.ijpharm.2014.07.015 · 3.65 Impact Factor
  • Natassa Pippa · Maria Mariaki · Stergios Pispas · Costas Demetzos
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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; 473(1-2). DOI:10.1016/j.ijpharm.2014.07.001 · 3.65 Impact Factor
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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. DOI:10.1166/jnn.2014.9026 · 1.34 Impact Factor
  • Natassa Pippa · Eleni Kaditi · Stergios Pispas · Costas Demetzos
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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.
    06/2014; 6(6). DOI:10.1166/asem.2014.1554
  • Natassa Pippa · Stergios Pispas · Costas Demetzos
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    ABSTRACT: In this work, we investigate the alterations of the physicochemical, morphological, and thermotropic characteristics of conventional, stealth, and chimeric DPPC (dipalmitoylphosphatidylcholine) liposomes, caused by the incorporation of PEGylated lipid and block copolymers with different architectures and compositions. 1,2-Dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[Methoxy(Polyethylene glycol)-3000] (DPPE-PEG 3000) is the PEGylated lipid, poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) is the block copolymer, and poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline) (MPOx) is the gradient block copolymer, which are selected for preparing the liposomal systems. Light scattering techniques and differential scanning calorimetry (DSC) were used in order to extract information on the physicochemical/thermodynamic balance of the prepared liposomal systems. The physicochemical characteristics and the morphology via fractal analysis of these chimeric nanoassemblies were found to depend on the composition of the polymeric component, while DPPC liposomes were used for comparison reasons (reference system). The incorporation of polymeric components into liposomes promotes a structural rearrangement of lipid bilayers and affects their behavior, as DSC experiments indicated. The fluidity, the intervesicle interactions and the cooperativity of structural elements of liposomes were also changed significantly by polymer addition. It could be concluded that the different macromolecular architectures of the polymeric guest affect the thermotropic behavior of liposomal membrane by producing new metastable phases, and consequently promote new insights in the field of biophysical concept for designing and developing chimeric advanced drug delivery nano systems (aDDnSs).
    Journal of Thermal Analysis and Calorimetry 04/2014; 120(1). DOI:10.1007/s10973-014-4116-5 · 2.21 Impact Factor
  • Costas Demetzos
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    ABSTRACT: Guest EditorProf. Costas DemetzosIn Pharmaceutical Technology and Nano-technologyDirector of the Laboratory of Pharmaceutical TechnologyFaculty of Pharmacy, University of Athens, GreeceE-mail: demetzos@pharm.uoa.grThis compilation is based on the peer-reviewed and selected papers presented at MEDICTA2013 conference.PrefaceThis is a Special Chapter of the Journal of Thermal Analysis and Calorimetry comprising 18 peer-reviewed articles on recent advances in the field of Thermal Analysis, suitable for everyone interested in this field. These advances are related to the thermal processes occurring in materials contributing in a wide spectrum of everyday life activities. All the articles are considered as high impact and scientists from different scientific fields were welcomed to submit their research for evaluation. The topics covered in this Special Chapter include Engineering, Drug development, Cultural Heritage, Biology, and Miscellaneous. I have to point out that the presented article ...
    Journal of Thermal Analysis and Calorimetry 04/2014; 116(1):1-3. DOI:10.1007/s10973-013-3616-z · 2.21 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; 24(3). DOI:10.3109/08982104.2014.891232 · 1.53 Impact Factor

Publication Stats

2k Citations
383.28 Total Impact Points

Institutions

  • 2005–2015
    • National and Kapodistrian University of Athens
      • • Department of Pharmaceutical Technology
      • • Division of Pharmacology
      Athínai, Attica, Greece
  • 1994–2014
    • Harokopion University of Athens
      Athínai, Attica, Greece
  • 2001–2011
    • Julphar School of Pharmacy
      Greece, New York, United States
  • 2008
    • National Hellenic Research Foundation
      • Institute of Biology, Medicinal Chemistry and Biotechnology
      Athínai, Attica, Greece
  • 2006
    • University of Patras
      • Laboratory of Pharmacognosy and Chemistry of Natural Products
      Rhion, West Greece, Greece
  • 2000
    • IT University of Copenhagen
      København, Capital Region, Denmark