Compositions of Anticancer Drug with Micellar Nanocarriers and Their Cytotoxicity
Keywords:micelles, morphology, block copolymers, doxorubicin, cytotoxicity
AbstractAsymmetric 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. https://doi.org/10.1142/9781860949074
Mahmud A, Xiong X, Aliabadi H, Lavasanifar A. Polymeric micelles for drug targeting. Journal of Drug Targeting 2007;15(9):553-584. https://doi.org/10.1080/10611860701538586
Tong R, Cheng J. Anticancer Polymeric Nanomedicines. Polymer Reviews 2007;47(3):345-381. https://doi.org/10.1080/15583720701455079
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. https://doi.org/10.1016/j.cocis.2010.10.003
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. https://doi.org/10.1098/rsif.2008.0547.focus
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. https://doi.org/10.1016/j.jconrel.2011.08.009
Ohya Y, Takahashi A, Nagahama K. Biodegradable Polymeric Assemblies for Biomedical Materials. Polymers in Nanomedicine 2011;:65-114. https://doi.org/10.1007/12_2011_160
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. https://doi.org/10.1039/c2cc32408c
Sutton D, Nasongkla N, Blanco E, Gao J. Functionalized Micellar Systems for Cancer Targeted Drug Delivery. Pharmaceutical Research 2007;24(6):1029-1046. https://doi.org/10.1007/s11095-006-9223-y
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. https://doi.org/10.1016/j.jconrel.2008.01.021
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. https://doi.org/10.1002/pola.23036
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. https://doi.org/10.1039/b822319j
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. https://doi.org/10.1016/j.carbpol.2011.06.004
Chatterjee K, Zhang J, Honbo N, Karliner J. Doxorubicin Cardiomyopathy. Cardiology 2010;115(2):155-162. https://doi.org/10.1159/000265166
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. https://doi.org/10.1002/mabi.200900233
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. https://doi.org/10.1016/j.jconrel.2009.04.019
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. https://doi.org/10.1021/bm800043n
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/-281/. https://doi.org/10.1080/15421400802463092
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/-159/. https://doi.org/10.1080/15421406.2011.538595
Zheltonozhskaya T, Permyakova N, Momot L. INTRAMOLECULAR POLYCOMPLEXES IN BLOCK AND GRAFT COPOLYMERS. Hydrogen-Bonded Interpolymer Complexes 2009;:85-154. https://doi.org/10.1142/9789812709776_0005
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/-61/. https://doi.org/10.1080/15421400701229453
Pretsch E, Bühlmann P, Affolter C. Combination Tables. Structure Determination of Organic Compounds 2000;:49-69. https://doi.org/10.1007/978-3-662-04201-4_3
Bellamy L. Alkenes. The Infra-red Spectra of Complex Molecules 1975;:37-63. https://doi.org/10.1007/978-94-011-6017-9_3
Riess G. Micellization of block copolymers. Progress in Polymer Science 2003;28(7):1107-1170. https://doi.org/10.1016/s0079-6700(03)00015-7
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. https://doi.org/10.1002/mabi.200800163
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. https://doi.org/10.2147/ijn.s23099
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. https://doi.org/10.1002/mabi.200700290
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. https://doi.org/10.1186/1556-276x-7-687
Authors who publish with this journal agree to the following terms:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).