Liposomes and dendritic polymers as drug delivery systems

Our work is focused on the functionalization, physicochemical characterization and drug encapsulation of functional nanomaterials, mainly liposomes and dendritic polymers, giving emphasis on their applications as targeted and controlled release drug delivery systems.

The group has been for many years active in the development of functional dendritic polymers for drug delivery,1-7 and is currently extensively focused on their application for cell mitochondria targeting,8-13 or as thermoresponsive drug delivery systems14 aiming at improved in vitro cytotoxicity and reduction of side effects. 

Confocal images depicting mitochondrial targeting employing triphenylphosphonium functionalized polyethyleneimine.

Confocal images of doxorubicin cell internalization employing thermoresponsive hyperbranched polyethyleneimine.

Liposomal research is currently focused on the development of novel thermoresponsive liposomal drug delivery systems employing both experimental and computational techniques that exhibit, in combination with hyperthermia, passive targeting, cell nuclei internalization and improved cytotoxicity.15-16

Confocal images depicting of doxorubicin cell internalization employing novel thermoresponsive liposomes.

Selected recent publications

  1. Z. Sideratou, D. Tsiourvas, T. Theodossiou, M. Fardis, C. M. Paleos, Synthesis and characterization of multifunctional hyperbranched polyesters as prospective contrast agents for targeted MRI, Bioorg. Med. Chem. Lett. 20, 4177-4181 (2010).
  2. Z. Sideratou, N. Sterioti, D. Tsiourvas, L.-A. Tziveleka, A. Thanassoulas, G. Nounesis, C. M. Paleos, Arginine end-functionalized poly(L-lysine) dendrigrafts for the stabilization and controlled release of insulin, J. Colloid Interface Sci. 351, 433-441 (2010).
  3. Z. Sideratou, C. Kontoyianni,G. I. Drossopoulou, C. M. Paleos, Synthesis of a folate functionalized PEGylated poly(propylene imine) dendrimer as prospective targeted drug delivery system, Bioorg. Med. Chem. Lett. 20, 6513–6517 (2010).
  4. C. M. Paleos, D. Tsiourvas, Z. Sideratou, L.-A. Tziveleka, Drug Delivery Employing Multifunctional Dendrimers and Hyperbranched Polymers, Expert Opinion on Drug Delivery, 7, 1387-1398 (2010).
  5. D. Tsiourvas, Z. Sideratou, N. Sterioti, A. Papadopoulos, G. Nounesis, C. M. Paleos, Insulin Complexes with PEGylated Basic Oligopeptides, J. Colloid Interface Sci. 384, 61–72 (2012).
  6. C. M. Paleos, Z. Sideratou, Th. A. Theodossiou, D. Tsiourvas, Carboxylated Hydroxyethyl Starch: A novel Polysaccharide for the Delivery of Doxorubicin, Chem. Biol. Drug Des. 85, 653–658 (2015).
  7. C. M. Paleos, Z. Sideratou, D. Tsiourvas, Drug Delivery Systems Based on Hydroxyethyl Starch, Bioconjugate Chem. 28, 1611–1624 (2017).
  8. T. A. Theodossiou, Z. Sideratou, D. Tsiourvas, C. M. Paleos, A Novel mitotropic oligolysine nanocarrier: Targeted delivery of covalently bound d-luciferin to cell mitochondria, Mitochodrion, 11, 982-986 (2011).
  9. T. A. Theodossiou, Z. Sideratou, M. Katsarou, D. Tsiourvas, Mitochondrial delivery of doxorubicin by triphenylphosphonium-functionalized hyperbranched poly(ethylene imine) nanocarriers results in a rapid and severe DU145 cytocide, Pharm. Res. 30, 2832–2842 (2013).
  10. C. M. Paleos, D. Tsiourvas, Z. Sideratou, Triphenylphosphonium Decorated Liposomes and Dendritic Polymers: Prospective Second Generation Drug Delivery Systems for Targeting Mitochondria, Mol. Pharmaceutics 13, 2233–2241 (2016).
  11. K.N. Panagiotaki, Z. Sideratou, S.A. Vlahopoulos, M. Paravatou-Petsotas, M. Zachariadis, N. Khoury, V. Zoumpourlis, D. Tsiourvas, A Triphenylphosphonium-Functionalized Mitochondriotropic Nanocarrier for Efficient Co-Delivery of Doxorubicin and Chloroquine and Enhanced Antineoplastic Activity, Pharmaceuticals (Basel) 10 Article ID: E912017 (2017). DOI: 10.3390/ph10040091.
  12. V. Stagni, A. Kaminari, Z. Sideratou, E. Sakellis, S.A. Vlahopoulos, D. Tsiourvas, Targeting breast cancer stem-like cells using chloroquine encapsulated by a triphenylphosphonium-functionalized hyperbranched polymer. Int. J. Pharm., 585, 119465 (2020). DOI: 10.1016/j.ijpharm.2020.119465.
  13. D. Tsiourvas, Z. Sideratou, S. Vlachopoulos, “Innovative mitochondria-targeted drug delivery systems of aminoquinolines and of their derivatives based on dendritic polymers” Filed in Greek Patent Office, Application Number: 20160100398/11-7-2016. Patent number 1009107/08-09-2017.
  14. Z. Sideratou, M. Agathokleous, T. A. Theodossiou, D. Tsiourvas, Functionalized Hyperbranched Polyethyleneimines as Thermosensitive Drug Delivery Nanocarriers with Controlled Transition Temperatures, Biomacromolecules, 19, 315-328 (2018).
  15. K. Eleftheriou, A. Kaminari, K. N. Panagiotaki, Z. Sideratou, M. Zachariadis, J. Anastassopoulou, D. Tsiourvas, A combination drug delivery system employing thermosensitive liposomes for enhanced cell penetration and improved in vitro efficacy, Int. J. Pharm., 574, 118912 (2020). DOI:10.1016/j.ijpharm.2019.118912.
  16. K. Eleftheriou, Z. Sideratou, A. Thanassoulas, A. Papakyriakou, D. Tsiourvas, Comparative Experimental and Computational Study of Monoalkyl Chain Phosphatidylcholine-Containing Thermoresponsive Liposomes, J. Phys. Chem. B 120, 5417–5428 (2016)

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