Compositions of Anticancer Drug with Micellar Nanocarriers and Their Cytotoxicity


  • Larisa Kunitskaya Taras Shevchenko National University of Kiev
  • Tatyana Zheltonozhskaya Taras Shevchenko National University of Kiev
  • Rostyslav Stoika Institute of Cell Biology NAS of Ukraine
  • Dmytro Klymchuk Institute of Botany NAS of Ukraine



micelles, morphology, block copolymers, doxorubicin, cytotoxicity


Asymmetric diblock (DBC) and triblock (TBC) copolymers contained biocompatible chemically complementary polyacrylamide and poly(ethylene oxide) (PAAm-b-PEO-b-PAAm) or its monomethyl ether (MEPEO-b-PAAm), and also partially hydrolyzed triblock copolymer derivative (TBChydr) were used to create micelles of a special type. The micelles obtained are characterized by small CMCs and large values of the Gibbs micellization energy, thus indicating a high stability of DBC, TBC and TBChydr micelles in aqueous solutions and the capabilities of their use to encapsulate and deliver poorly soluble and/or toxic drugs in living organism. Morphological features and size of DBC and TBC micelles were determined by TEM. The electron images demonstrated spherical micelles of a polymolecular type, monomolecular type and separate micelle aggregates. TBC and TBChydr micelles were used to examine in vitro anticancer activity of their compositions with doxorubicin (Dox). The created micelle systems showed the enhanced cytotoxicity as compared to individual Dox against murine leukemia cells of L1210 line, murine transformed fibroblasts of L929 line and human T-leukemia cells of Jurkat line and allow to achieve a high efficacy at low Dox concentrations (0,1÷3 µg·cm-3) that opens the great prospects for essential decrease in drug dose at  chemotherapy.


Torchilin V. Nanoparticulates as drug carriers. Imperial College Press, London; 2006, pp.58-62.

Mahmud A, Xiong X, Aliabadi H, Lavasanifar A. Polymeric micelles for drug targeting. Journal of Drug Targeting 2007;15(9):553-584.

Tong R, Cheng J. Anticancer Polymeric Nanomedicines. Polymer Reviews 2007;47(3):345-381.

Ebrahim Attia A, Ong Z, Hedrick J, Lee P, Ee P, Hammond P, Yang Y. Mixed micelles self-assembled from block copolymers for drug delivery. Current Opinion in Colloid & Interface Science 2011;16(3):182-194.

Osada K, Christie R, Kataoka K. Polymeric micelles from poly(ethylene glycol)-poly(amino acid) block copolymer for drug and gene delivery. Journal of The Royal Society Interface 2009;6(Suppl_3):S325-S339.

Dane K, Nembrini C, Tomei A, Eby J, O'Neil C, Velluto D, Swartz M, Inverardi L, Hubbell J. Nano-sized drug-loaded micelles deliver payload to lymph node immune cells and prolong allograft survival. Journal of Controlled Release 2011;156(2):154-160.

Ohya Y, Takahashi A, Nagahama K. Biodegradable Polymeric Assemblies for Biomedical Materials. Polymers in Nanomedicine 2011;:65-114.

Zhang Q, Re Ko N, Kwon Oh J. Recent advances in stimuli-responsive degradable block copolymer micelles: synthesis and controlled drug delivery applications. Chemical Communications 2012;48(61):7542.

Sutton D, Nasongkla N, Blanco E, Gao J. Functionalized Micellar Systems for Cancer Targeted Drug Delivery. Pharmaceutical Research 2007;24(6):1029-1046.

Wang Y, Liu X, Sun T, Xiong M, Wang J. Functionalized micelles from block copolymer of polyphosphoester and poly(ɛ-caprolactone) for receptor-mediated drug delivery. Journal of Controlled Release 2008;128(1):32-40.

Noh T, Kook Y, Park C, Youn H, Kim H, Oh E, Choi E, Park H, Kim C. Block copolymer micelles conjugated with anti-EGFR antibody for targeted delivery of anticancer drug. Journal of Polymer Science Part A: Polymer Chemistry 2008;46(22):7321-7331.

Shi M, Lu J, Shoichet M. Organic nanoscale drug carriers coupled with ligands for targeted drug delivery in cancer. Journal of Materials Chemistry 2009;19(31):5485.

Freichels H, Jérôme R, Jérôme C. Sugar-labeled and PEGylated (bio)degradable polymers intended for targeted drug delivery systems. Carbohydrate Polymers 2011;86(3):1093-1106.

Chatterjee K, Zhang J, Honbo N, Karliner J. Doxorubicin Cardiomyopathy. Cardiology 2010;115(2):155-162.

Sakthibalan M, Sawadkar MS, Asmathulla S, Ivan EA, Muthu G. Study of cardioprotective effect of N-acetilcysteine, Vitamine C and Enalapril given incombination to prevent doxorubicin induced cardio toxicity in Wistar rats. Pharm. Biomed. Sci 2013;36:1902-1908

Glen S, Marcus L. inventor; Wisconsin Alumni Research Foundation, assignee. Micelle composition of polymer and passenger drug. United States patent 8 173 167. 2012 May 8.

Xu Y, Meng F, Cheng R, Zhong Z. Reduction-Sensitive Reversibly Crosslinked Biodegradable Micelles for Triggered Release of Doxorubicin. Macromolecular Bioscience 2009;9(12):1254-1261.

Heller G, Ng SY, inventors; Advanced Polymer Systems, Inc., assignee. PEG-POE, PEG-POE-PEG and POEPEG-POE block copolymers. United States Patent 5 939 453.1999 Aug 17.

Kim J, Kabanov A, Bronich T. Polymer micelles with cross-linked polyanion core for delivery of a cationic drug doxorubicin. Journal of Controlled Release 2009;138(3):197-204.

Chan Y, Wong T, Byrne F, Kavallaris M, Bulmus V. Acid-Labile Core Cross-Linked Micelles for pH-Triggered Release of Antitumor Drugs. Biomacromolecules 2008;9(7):1826-1836.

Fedorchuk S, Zheltonozhskaya T, Permyakova N, Gomza Y, Nessin S, Klepko V. Structural Peculiarities of Triblock Copolymers Containing Poly(Ethylene Oxide) and Polyacrylamide. Molecular Crystals and Liquid Crystals 2008;497(1):268/[600]-281/[613].

Zheltonozhskaya T, Nedashkovskaya V, Khutoryanskiy V, Gomza Y, Fedorchuk S, Klepko V, Partsevskaya S. Micelles of PAAm-b-PEO-b-PAAm Triblock Copolymers and Their Binding with Prednisolon. Molecular Crystals and Liquid Crystals 2011;536(1):148/[380]-159/[391].

Zheltonozhskaya T, Permyakova N, Momot L. INTRAMOLECULAR POLYCOMPLEXES IN BLOCK AND GRAFT COPOLYMERS. Hydrogen-Bonded Interpolymer Complexes 2009;:85-154.

Permyakova N, Zheltonozhskaya T, Fedorchuk S, Zagdanskaya N, Syromyatnikov V. Temperature Effect on Hydrogen Bonds in Triblock Copolymers of Poly(Ethylene Oxide) and Polyacrylamide. Molecular Crystals and Liquid Crystals 2007;468(1):53/[405]-61/[413].

Pretsch E, Bühlmann P, Affolter C. Combination Tables. Structure Determination of Organic Compounds 2000;:49-69.

Bellamy L. Alkenes. The Infra-red Spectra of Complex Molecules 1975;:37-63.

Riess G. Micellization of block copolymers. Progress in Polymer Science 2003;28(7):1107-1170.

Lavignac N, Nicholls J, Ferruti P, Duncan R. Poly(amidoamine) Conjugates Containing Doxorubicin Bound via an Acid-Sensitive Linker. Macromolecular Bioscience 2009;9(5):480-487.

Han M, Diao , Fu , Hu , Jiang , Tsutsumi , Wei , Chen , Gao J. Doxorubicin-loaded PEG-PCL copolymer micelles enhance cytotoxicity and intracellular accumulation of doxorubicin in adriamycin-resistant tumor cells. International Journal of Nanomedicine 2011;:1955.

Zarabi B, Nan A, Zhuo J, Gullapalli R, Ghandehari H. HPMA Copolymer-Doxorubicin-Gadolinium Conjugates: Synthesis, Characterization, andin vitroEvaluation. Macromolecular Bioscience 2008;8(8):741-748.

Amjad M, Amin M, Katas H, Butt A. Doxorubicin-loaded cholic acid-polyethyleneimine micelles for targeted delivery of antitumor drugs: synthesis, characterization, and evaluation of their in vitro cytotoxicity. Nanoscale Research Letters 2012;7(1):687.