Download PDF
Drug Res (Stuttg) 2017; 67(04): 228-238
DOI: 10.1055/s-0042-124190
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Synthesis and Evaluation of a Triblock Copolymer/ZnO Nanoparticles from Poly(ε-caprolactone) and Poly(Acrylic Acid) as a Potential Drug Delivery Carrier

Lida Ahmadkhani
1   Lab. of Nano, Faculty of Chemistry, Payame Noor University, Iran
,
Ali Baghban
1   Lab. of Nano, Faculty of Chemistry, Payame Noor University, Iran
,
Shahram Mohammadpoor
2   Dipartimento di Chimica, Materiali eingeneria Chimica “Giulio Natta” Politecnico di Milano-Italia
,
Rovshan Khalilov
3   Faculty of Biology, Department of Biophysics and Molecular Biology, Baku State University, Baku, Azerbaijan Republic
5   Joint Ukrainian-Azerbaijan International Research and Education Center Of Nanobiotechnology and Functional Nanosystems, Drohobych Ukraine & Baku, Azerbaijan
7   Institute of Radiation Problems, National Academy of Sciences of Azerbaijan, Baku, Azerbaijan
,
Abolfazl Akbarzadeh
4   Stem Cell Research Center,Tabriz University of Medical Sciences, Tabriz, Iran
5   Joint Ukrainian-Azerbaijan International Research and Education Center Of Nanobiotechnology and Functional Nanosystems, Drohobych Ukraine & Baku, Azerbaijan
6   Universal Scientific Education and Research Network (USERN), Tabriz, Iran
,
Taras Kavetskyy
5   Joint Ukrainian-Azerbaijan International Research and Education Center Of Nanobiotechnology and Functional Nanosystems, Drohobych Ukraine & Baku, Azerbaijan
8   The John Paul II Catholic University of Lublin, Lublin, Poland
,
Siamak Saghfi
3   Faculty of Biology, Department of Biophysics and Molecular Biology, Baku State University, Baku, Azerbaijan Republic
5   Joint Ukrainian-Azerbaijan International Research and Education Center Of Nanobiotechnology and Functional Nanosystems, Drohobych Ukraine & Baku, Azerbaijan
,
Aygun N. Nasibova
5   Joint Ukrainian-Azerbaijan International Research and Education Center Of Nanobiotechnology and Functional Nanosystems, Drohobych Ukraine & Baku, Azerbaijan
7   Institute of Radiation Problems, National Academy of Sciences of Azerbaijan, Baku, Azerbaijan
› Author Affiliations
Further Information

Publication History

Received 23 July 2016

Accepted 01 December 2016

Publication Date:
14 February 2017 (online)

Also available at
    Permissions and Reprints

Abstract

Through the present paper, a triblock copolymer containing pH-responsive (polyacrylic acid-b-polycaprolactone -b-polyacrylic acid) (PAA-b-PCL-b-PAA) was synthesized by using the ring-opening polymerization (ROP) of ε-caprolactone (ε-CL) and the reversible addition fragmentation chain transfer (RAFT) polymerization of the acrylic acid methods, as the drug carrier. Blends of the nanocrystalline zinc oxide nanoparticles (n-ZnO) and triblock copolymer treated from the solution have been used to make the hybrid polymer-metal oxide for the preparation of the drug loaded nanocomposite. The drug-release behavior of the nanocomposite was studied by using the Doxorubicin as a model drug. In addition to the self-assembly and pH-responsive behavior of the triblock copolymers/ZnO was studied in solution by the Fluorescence Spectroscopy, Scanning Electron Microscopy(SEM), Transmission Electron Microscopy (TEM), DLS, HNMR and FT-IR spectroscopy.

Key words

triblock copolymer - RAFT Polymerization - Polyacrylic acid - poly caprolactone - nanocomposite - drug delivery
 

  • References

  • 1 Allen TM. Ligand-targeted therapeutics in anticancer therapy. Nature Reviews Cancer 2002; 2: 750
    CrossrefPubMedGoogle Scholar
  • 2 Croix BS, Rago C, Velculescu V. et al. Genes expressed in human tumor endothelium. Science 2000; 289: 1197
    CrossrefPubMedGoogle Scholar
  • 3 Torchilin VP. Multifunctional nanocarriers. Advanced drug delivery reviews 2012; 64: 302
    CrossrefPubMedGoogle Scholar
  • 4 Torchilin VP. Multifunctional nanocarriers. Advanced Drug Delivery Reviews 2006; 58: 1532
    CrossrefPubMedGoogle Scholar
  • 5 Young RCb, Ozols RF, Myers CE. The anthracycline antineoplastic drugs. New England Journal of Medicine 1981; 305: 139
    CrossrefPubMedGoogle Scholar
  • 6 Vauthier C, Dubernet C, Chauvierre C. et al. Drug delivery to resistant tumors: the potential of poly (alkyl cyanoacrylate) nanoparticles. Journal of Controlled Release 2003; 93: 151
    CrossrefPubMedGoogle Scholar
  • 7 Bibby DC, Talmadge JE, Dalal MK. et al. Pharmacokinetics and biodistribution of RGD-targeted doxorubicin-loaded nanoparticles in tumor-bearing mice. International journal of pharmaceutics 2005; 293: 281
    CrossrefPubMedGoogle Scholar
  • 8 Peer D, Margalit R. Tumor-targeted hyaluronan nanoliposomes increase the anti tumor activity of liposomal doxorubicin in syngeneic and human xenograft mouse tumor models. NEOPLASIA-NEW YORK THEN ANN ARBOR 2004; 6: 343
    PubMedGoogle Scholar
  • 9 Lavignac N, Nicholls J, Ferruti P. et al. Poly (amidoamine) Conjugates Containing Doxorubicin Bound via an Acid-Sensitive Linker. Macromolecular bioscience 2009; 9: 480
    CrossrefPubMedGoogle Scholar
  • 10 Guan H, McGuire M, Li S. et al. Peptide-targeted polyglutamic acid doxorubicin conjugates for the treatment of αvβ6-positive cancers. Bioconjugate chemistry 2008; 19: 1813
    CrossrefPubMedGoogle Scholar
  • 11 Etrych T, Chytil P, Mrkvan T. et al. Conjugates of doxorubicin with graft HPMA copolymers for passive tumor targeting. Journal of Controlled Release 2008; 132: 184
    CrossrefPubMedGoogle Scholar
  • 12 Moses MA, Brem H, Langer R. Advancing the field of drug delivery: taking aim at cancer. Cancer cell 2003; 4: 337
    CrossrefPubMedGoogle Scholar
  • 13 Duncan R. The dawning era of polymer therapeutics. Nature Reviews Drug Discovery 2003; 2: 347
    CrossrefPubMedGoogle Scholar
  • 14 Kang XJ, Dai YL, Ma P. et al. Poly (acrylic acid)-modified Fe3O4 microspheres for magnetic-targeted and ph-triggered anticancer drug delivery. Chemistry – A European Journal 2012; 18: 15676
    CrossrefPubMedGoogle Scholar
  • 15 Seow WY, Xue JM, Yang YY. Targeted and intracellular delivery of paclitaxel using multi-functional polymeric micelles. Biomaterials 2007; 28: 1730
    CrossrefPubMedGoogle Scholar
  • 16 Soppimath KS, Liu L, Seow W. et al. Multifunctional core/shell nanoparticles self-assembled from pH-induced thermosensitive polymers for targeted intracellular anticancer drug delivery. Advanced Functional Materials 2007; 17: 355
    CrossrefPubMedGoogle Scholar
  • 17 Alizadeh E, Eslaminejad MRB, Akbarzadeh A . et al. Upregulation of MiR – 122 via Trichostatin A Treatments in Hepatocyte – like Cells Derived from Mesenchymal Stem Cells. Chemical Biology & Drug Design 2015; 87: 296-305
    PubMedGoogle Scholar
  • 18 Akbarzadeh A, Mikaeili H, Zarghami N. et al. Preparation and in vitro evaluation of doxorubicin-loaded Fe. International journal of nanomedicine 2012; 7: 511
    PubMedGoogle Scholar
  • 19 Hiljanen V, Karjalainen T, Seppälä J. Biodegradable lactone copolymers. I. Characterization and mechanical behavior of ε-caprolactone and lactide copolymers. Journal of applied polymer science 1996; 59: 1281
    CrossrefPubMedGoogle Scholar
  • 20 Liu F, Eisenberg A. Preparation and pH triggered inversion of vesicles from poly (acrylic acid)-b lock-polystyrene-b lock-Poly (4-vinyl pyridine). Journal of the American Chemical Society 2003; 125: 15059
    CrossrefPubMedGoogle Scholar
  • 21 Karanikolas A, Tsolakis P, Bokias G. et al. Stimuli-responsive poly (ethylene oxide)-b-poly (2-vinylpyridine)-b-poly (ethylene oxide) triblock copolymers and complexation with poly (acrylic acid) at low pH. The European Physical Journal E 2008; 27: 335
    CrossrefPubMedGoogle Scholar
  • 22 Guice KB, Marrou SR, Gondi SR. et al. pH Response of model diblock and triblock copolymer networks containing polystyrene and poly (2-hydroxyethyl methacrylate-co-2-(dimethylamino) ethyl. Macromolecules 2008; 41: 4390
    CrossrefPubMedGoogle Scholar
  • 23 Mohammad HR, Effat A, Behrouz I. Recurrent laryngeal papillomatosis with bronchopulmonary spread in a 70-year-old man . Tuberk Toraks 2007; 55: 299-330
    PubMedGoogle Scholar
  • 24 Tian Y, Bromberg L, Lin SN. et al. Complexation and release of doxorubicin from its complexes with pluronic P85-b-poly (acrylic acid) block copolymers. Journal of Controlled Release 2007; 121: 137
    CrossrefPubMedGoogle Scholar
  • 25 Hrubý M, Koňák Č, Ulbrich K. Polymeric micellar pH-sensitive drug delivery system for doxorubicin. Journal of Controlled Release 2005; 103: 137
    CrossrefPubMedGoogle Scholar
  • 26 Choo ESG, Yu B, Xue J. Synthesis of poly (acrylic acid)(PAA) modified Pluronic P123 copolymers for pH-stimulated release of doxorubicin. Journal of colloid and interface science 2011; 358: 462
    CrossrefPubMedGoogle Scholar
  • 27 Shivananju B, Prashanth GR, Asokan S. et al. Reversible and irreversible pH induced conformational changes in self-assembled weak polyelectrolyte multilayers probed using etched fiber Bragg grating sensors. Sensors and Actuators B: Chemical 2014; 201: 37
    CrossrefPubMedGoogle Scholar
  • 28 Favier A, Charreyre MT. Experimental requirements for an efficient control of free-radical polymerizations via the reversible addition-fragmentation chain transfer (RAFT) process. Macromolecular Rapid Communications 2006; 27: 653
    CrossrefPubMedGoogle Scholar
  • 29 Daraee H, Eatemadi A, Abbasi E. et al. Application of gold nanoparticles in biomedical and drug delivery. Artificial cells, nanomedicine, and biotechnology 2014; 44: 410-422
    PubMedGoogle Scholar
  • 30 McCormick CL, Lowe AB.. Aqueous RAFT polymerization: recent developments in synthesis of functional water-soluble (co) polymers with controlled structures. Accounts of chemical research 2004; 37: 312
    CrossrefPubMedGoogle Scholar
  • 31 Sobani M, Haddadi-Asl V, Salami M. et al. Grafting through” approach for synthesis of polystyrene/silica aerogel nanocomposites by in situ reversible addition-fragmentation chain transfer polymerization. Journal of sol-gel science and technology 2013; 66: 337
    PubMedGoogle Scholar
  • 32 Hong H, Shi J, Yang Y. et al. Cancer-targeted optical imaging with fluorescent zinc oxide nanowires. Nano letters 2011; 11: 3744
    CrossrefPubMedGoogle Scholar
  • 33 Daraee H, Etemadi A, Kouhi M. et al. Application of liposomes in medicine and drug delivery. Artificial cells, nanomedicine, and biotechnology 2014; 44: 381-391
    PubMedGoogle Scholar
  • 34 Mohammad HR, Effat A, Reza S. et al. Aquatic leech as a rare cause of respiratory distress and hemoptysis. Pneumologia (Bucharest, Romania) 2011; 60: 85-86
    PubMedGoogle Scholar
  • 35 Akmal H, Hairul N, Zulfakar M. et al. Controlled/living radical polymerization of methyl methacrylate in the presence of 2-bromoethanol as a transfer agent and comparison with cumyl. Journal of Applied Sciences 2009; 9: 3146
    CrossrefPubMedGoogle Scholar
  • 36 Le TP, Moad G, Rizzardo E. et al. PCT Int Appl WO 9801478 A1 980115. In Chem Abstr 1998; 128: 115390
    PubMedGoogle Scholar
  • 37 Kwon GS, Naito M, Yokoyama M. et al. Physical entrapment of adriamycin in AB block copolymer micelles. Pharmaceutical Research 1995; 12: 192
    CrossrefPubMedGoogle Scholar
  • 38 Yuyama Y, Tsujimoto M, Fujimoto Y. et al. Potential usage of thermosensitive liposomes for site-specific delivery of cytokines. Cancer Letters 2000; 155: 71
    CrossrefPubMedGoogle Scholar
  • 39 Willcock H, O'Reilly RK. End group removal and modification of RAFT polymers. Polymer Chemistry 2010; 1: 149
    CrossrefPubMedGoogle Scholar
  • 40 Abbasi E, Akbarzadeh A, Kouhi M. et al. Graphene: Synthesis, Bio-Applications, and Properties. Artificial Cells, Nanomedicine, and Biotechnology 2014; 44: 150-156
    PubMedGoogle Scholar
  • 41 Chiefari J, Chong YK, Ercole F. et al. Living free-radical polymerization by reversible addition-fragmentation chain transfer: the RAFT process. Macromolecules 1998; 31: 5559
    CrossrefPubMedGoogle Scholar
  • 42 Mayadunne RT, Jeffery J, Moad G. et al. Living free radical polymerization with reversible addition-fragmentation chain transfer (RAFT polymerization): approaches to star polymers. Macromolecules 2003; 36: 1505
    CrossrefPubMedGoogle Scholar
  • 43 Harrigan PR, Wong KF, Redelmeier TE. et al. Accumulation of doxorubicin and other lipophilic amines into large unilamellar vesicles in response to transmembrane pH gradients. Biochimica et Biophysica Acta (BBA)-Biomembranes 1993; 1149: 329
    CrossrefPubMedGoogle Scholar
  • 44 Li G, Song S, Guo L. et al. Self-assembly of thermo-and pH-responsive poly (acrylic acid) - b-poly (N-isopropylacrylamide) micelles for drug delivery. Journal of Polymer Science Part A: Polymer Chemistry 2008; 46: 5028
    CrossrefPubMedGoogle Scholar
  • 45 Eatemadi A, Daraee H, Zarghami N. et al. Nanofiber; Synthesis and Biomedical Applications. Artificial Cells, Nanomedicine, and Biotechnology. Artificial Cells, Nanomedicine, and Biotechnology 2014; 44: 111-121
    PubMedGoogle Scholar
  • 46 Gaucher G, Dufresne M, Sant VP. et al. Block copolymer micelles: preparation, characterization and application in drug delivery. Journal of Controlled Release 2005; 109: 169
    CrossrefPubMedGoogle Scholar
  • 47 Sant VP, Smith D, Leroux J-C. Novel pH-sensitive supramolecular assemblies for oral delivery of poorly water soluble drugs: preparation and characterization. Journal of Controlled Release 2004; 97: 301
    CrossrefPubMedGoogle Scholar