Delivery Systems for Birch-bark Triterpenoids and their Derivatives in Anticancer Research

Author(s): Inese Mierina, Reinis Vilskersts, Māris Turks*

Journal Name: Current Medicinal Chemistry

Volume 27 , Issue 8 , 2020

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Abstract:

Birch-bark triterpenoids and their semi-synthetic derivatives possess a wide range of biological activities including cytotoxic effects on various tumor cell lines. However, due to the low solubility and bioavailability, their medicinal applications are rather limited. The use of various nanotechnology-based drug delivery systems is a rapidly developing approach to the solubilization of insufficiently bioavailable pharmaceuticals. Herein, the drug delivery systems deemed to be applicable for birch-bark triterpenoid structures are reviewed. The aforementioned disadvantages of birch-bark triterpenoids and their semi-synthetic derivatives can be overcome through their incorporation into organic nanoparticles, which include various dendrimeric systems, as well as embedding the active compounds into polymer matrices or complexation with carbohydrate nanoparticles without covalent bonding. Some of the known triterpenoid delivery systems consist of nanoparticles featuring inorganic cores covered with carbohydrates or other polymers. Methods for delivering the title compounds through encapsulation and emulsification into lipophilic media are also suitable. Besides, the birch-bark triterpenoids can form self-assembling systems with increased bio-availability. Even more, the self-assembling systems are used as carriers for delivering other chemotherapeutic agents. Another advantage besides increased bioavailability and anticancer activity is the reduced overall systemic toxicity in most of the cases, when triterpenoids are delivered with any of the carriers.

Keywords: Betulin, betulinic acid, oleanolic acid, lupeol, semi-synthetic derivatives, drug delivery systems.

[1]
Krasutsky, P.A. Birch bark research and development. Nat. Prod. Rep., 2006, 23(6), 919-942.
[http://dx.doi.org/10.1039/b606816b] [PMID: 17119640]
[2]
Ferreira, J.P.A.; Quilhó, T.; Pereira, H. Characterization of Betula pendulaouter bark regarding cork and phloem components at chemical and structural levels in view of biorefinery integration. J. Wood Chem. Technol., 2017, 37(1), 10-25.
[http://dx.doi.org/10.1080/02773813.2016.1224248]
[3]
Kvasnica, M.; Urban, M.; Dickinson, N.J.; Sarek, J. Pentacyclic triterpenoids with nitrogen- and sulfur-containing heterocycles: synthesis and medicinal significance. Nat. Prod. Rep., 2015, 32(9), 1303-1330.
[http://dx.doi.org/10.1039/C5NP00015G] [PMID: 26030604]
[4]
Achrem-Achremowicz, J.; Janeczko, Z. Betulina - triterpen pentacykliczny. Wiadomości Chemiczne, 2003, 57(3-4), 223-246.
[5]
Alakurtti, S.; Mäkelä, T.; Koskimies, S.; Yli-Kauhaluoma, J. Pharmacological properties of the ubiquitous natural product betulin. Eur. J. Pharm. Sci., 2006, 29(1), 1-13.
[http://dx.doi.org/10.1016/j.ejps.2006.04.006] [PMID: 16716572 ]
[6]
Shi, W.; Tang, N.; Yan, W. Research, and development in betulin and betulinic acid derived triterpenoids. Mini Rev. Org. Chem., 2014, 11(3), 343-354.
[http://dx.doi.org/10.2174/1570193X1103140915112124]
[7]
Baglin, I.; Mitaine-Offer, A-C.; Nour, M.; Tan, K.; Cavé, C.; Lacaille-Dubois, M-A. A review of natural and modified betulinic, ursolic and echinocystic acid derivatives as potential antitumor and anti-HIV agents. Mini Rev. Med. Chem., 2003, 3(6), 525-539.
[http://dx.doi.org/10.2174/1389557033487917] [PMID: 12871156]
[8]
Yogeeswari, P.; Sriram, D. Betulinic acid and its derivatives: a review on their biological properties. Curr. Med. Chem., 2005, 12(6), 657-666.
[http://dx.doi.org/10.2174/0929867053202214] [PMID: 15790304]
[9]
Eiznhamer, D.A.; Xu, Z.Q. Betulinic acid: a promising anticancer candidate. IDrugs, 2004, 7(4), 359-373.
[PMID: 15057642]
[10]
Cichewicz, R.H.; Kouzi, S.A. Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. Med. Res. Rev., 2004, 24(1), 90-114.
[http://dx.doi.org/10.1002/med.10053] [PMID: 14595673]
[11]
Ali-Seyed, M.; Jantan, I.; Vijayaraghavan, K.; Bukhari, S.N.A. Betulinic acid: recent advances in chemical modifications, effective delivery, and molecular mechanisms of a promising anticancer therapy. Chem. Biol. Drug Des., 2016, 87(4), 517-536.
[http://dx.doi.org/10.1111/cbdd.12682] [PMID: 26535952]
[12]
Mukherjee, R.; Kumar, V.; Srivastava, S.K.; Agarwal, S.K.; Burman, A.C. Betulinic acid derivatives as anticancer agents: structure activity relationship. Anticancer. Agents Med. Chem., 2006, 6(3), 271-279.
[http://dx.doi.org/10.2174/187152006776930846] [PMID: 16712455]
[13]
Mullauer, F.B.; Kessler, J.H.; Medema, J.P. Betulinic acid, a natural compound with potent anticancer effects. Anticancer Drugs, 2010, 21(3), 215-227.
[http://dx.doi.org/10.1097/CAD.0b013e3283357c62] [PMID: 20075711]
[14]
Kashyap, D.; Sharma, A.; Tuli, H.S.; Punia, S.; Sharma, A.K. Ursolic acid and oleanolic acid: pentacyclic terpenoids with promising anti-inflammatory activities. Recent Pat. Inflamm. Allergy Drug Discov., 2016, 10(1), 21-33.
[http://dx.doi.org/10.2174/1872213X10666160711143904] [PMID: 27531153]
[15]
Parikh, N.R.; Mandal, A.; Bhatia, D.; Siveen, K.S.; Sethi, G.; Bishayee, A. Oleanane triterpenoids in the prevention and therapy of breast cancer: current evidence and future perspectives. Phytochem. Rev., 2014, 13(4), 793-810.
[http://dx.doi.org/10.1007/s11101-014-9337-5] [PMID: 25395898 ]
[16]
Wang, Y.Y.; Yang, Y.X.; Zhe, H.; He, Z.X.; Zhou, S.F. Bardoxolone methyl (CDDO-Me) as a therapeutic agent: an update on its pharmacokinetic and pharmacodynamic properties. Drug Des. Devel. Ther., 2014, 8, 2075-2088.
[http://dx.doi.org/10.2147/DDDT.S68872] [PMID: 25364233 ]
[17]
Wang, Y.Y.; Zhe, H.; Zhao, R. Preclinical evidences toward the use of triterpenoid CDDO-Me for solid cancer prevention and treatment. Mol. Cancer, 2014, 13, 30.
[http://dx.doi.org/10.1186/1476-4598-13-30] [PMID: 24552536 ]
[18]
Dehaen, W.; Mashentseva, A.A.; Seitembetov, T.S. Allobetulin and its derivatives: synthesis and biological activity. Molecules, 2011, 16(3), 2443-2466.
[http://dx.doi.org/10.3390/molecules16032443] [PMID: 21403601 ]
[19]
Jäger, S.; Laszczyk, M.N.; Scheffler, A. A preliminary pharmacokinetic study of betulin, the main pentacyclic triterpene from extract of outer bark of birch (Betulae alba cortex). Molecules, 2008, 13(12), 3224-3235.
[http://dx.doi.org/10.3390/molecules13123224] [PMID: 19104487 ]
[20]
Jäger, S.; Winkler, K.; Pfüller, U.; Scheffler, A. Solubility studies of oleanolic acid and betulinic acid in aqueous solutions and plant extracts of Viscum album L. Planta Med., 2007, 73(2), 157-162.
[http://dx.doi.org/10.1055/s-2007-967106] [PMID: 17415876 ]
[21]
Yalçın, S.; Özlüer, Ö.; Gündüz, U. Nanoparticle-based drug delivery in cancer: the role of cell membrane structures. Ther. Deliv., 2016, 7(11), 773-781.
[http://dx.doi.org/10.4155/tde-2016-0056] [PMID: 27790949 ]
[22]
Yin, J.; Chen, Y.; Zhang, Z-H.; Han, X. Stimuli-responsive block copolymer-based assemblies for cargo delivery and theranostic applications. Polymers (Basel), 2016, 8(7)E268
[http://dx.doi.org/10.3390/polym8070268] [PMID: 30974545]
[23]
Papachristos, A.; Pippa, N.; Demetzos, C.; Sivolapenko, G. Antibody-drug conjugates: a mini-review. The synopsis of two approved medicines. Drug Deliv., 2016, 23(5), 1662-1666.
[http://dx.doi.org/10.3109/10717544.2014.998323] [PMID: 25625494]
[24]
Valdés, K.; Morales, J.; Rodríguez, L.; Günther, G. Potential use of nanocarriers with pentacyclic triterpenes in cancer treatments. Nanomedicine (Lond.), 2016, 11(23), 3139-3156.
[http://dx.doi.org/10.2217/nnm-2016-0251] [PMID: 27809705]
[25]
Stahl, P.H.; Wermuth, C.G. Handbook of pharmaceutical salts. Properties, selection, and use. Eds, 2nd; Wiley-VCH, , 2011; p. 446.
[26]
Suresh, C.; Zhao, H.; Gumbs, A.; Chetty, C.S.; Bose, H.S. New ionic derivatives of betulinic acid as highly potent anti-cancer agents. Bioorg. Med. Chem. Lett., 2012, 22(4), 1734-1738.
[http://dx.doi.org/10.1016/j.bmcl.2011.12.102] [PMID: 22264477 ]
[27]
Sánchez-Muñoz, S.; Gómez-Ruiz, S.; Pérez-Quintanilla, D.; Morante-Zarcero, S.; Sierra, I.; Prashar, S.; Paschke, R.; Kaluđerović, G.N. Preliminary study of the anticancer applications of mesoporous materials functionalized with the natural product betulinic acid. ChemMedChem, 2012, 7(4), 670-679.
[http://dx.doi.org/10.1002/cmdc.201100588] [PMID: 22278996 ]
[28]
Hussein-Al-Ali, S.H.; Arulselvan, P.; Fakurazi, S.; Hussein, M.Z. The in vitro therapeutic activity of betulinic acid nanocomposite on breast cancer cells (MCF-7) and normal fibroblast cell (3T3). J. Mater. Sci., 2014, 49, 8171-8182.
[http://dx.doi.org/10.1007/s10853-014-8526-3]
[29]
Tan, J.M.; Karthivashan, G.; Arulselvan, P.; Fakurazi, S.; Hussein, M.Z. Sustained release and cytotoxicity evaluation of carbon nanotube-mediated drug delivery system from betulinic acid. J. Nanomater., , 2014.ID 862148.
[http://dx.doi.org/10.1155/2014/862148]
[30]
Yingling, Y.G.; Shapiro, B.A. RNA nanoparticles and nanotubes Int. Pat. Appl. 2008. 2008/039254,
[31]
Duicu, O.; Ciurlea, S.; Dehelean, C.; Ardelean, S.; Andrica, F.; Muntean, D.; Soica, C.; Antal, D.; Coricovac, D.; Pinzaru, I. Analysis of betulinic acid formulation on liver mitochondria isolated from mice with induced murine melanoma. Rev. Chim, 2014, 65(8), 956-959.
[32]
Earek, J.; Biedermann, D.; Hajdúch, M. Triterpenoid derivatives for treating tumor diseases and pharmaceutical composition in which the derivatives are comprised CZ Patent 301158, 2009.
[33]
Smith, J.; Pruett, S.; Lu, S.; Akshaya, R.; Laihing, S. Occidiofungin formulations and uses thereof Int. Pat. Appl. 2016. 2016/040940,
[34]
Hing, S.L.; Ravinchandran, A.; Escano, J.; Cooley, J.; Autin, F.; Lu, S-E.; Pruett, S.; Smith, L. Toxicological evaluation of occidiofungin against mice and human cancer cell lines. Pharmacol. Pharm., 2014, 5, 1085-1093.
[http://dx.doi.org/10.4236/pp.2014.511118]
[35]
Godugu, C.; Patel, A.R.; Doddapaneni, R.; Somagoni, J.; Singh, M. Approaches to improve the oral bioavailability and effects of novel anticancer drugs berberine and betulinic acid. PLoS One, 2014, 9(3)e89919
[http://dx.doi.org/10.1371/journal.pone.0089919] [PMID: 24614362]
[36]
Dai, L.; Yang, T.; He, J.; Deng, L.; Liu, J.; Wang, L.; Lei, J.; Wang, L. Cellulose-graft-poly(L-lactic acid) nanoparticles for efficient delivery of anti-cancer drugs. J. Mater. Chem. B Mater. Biol. Med., 2014, 2, 6749-6757.
[http://dx.doi.org/10.1039/C4TB00956H]
[37]
Dai, L.; Liu, K-F.; Si, C-L.; He, J.; Lei, J-D.; Guo, L-Q. A novel self-assembled targeted nanoparticle platform based on carboxymethylcellulose co-delivery of anticancer agent. J. Mater. Chem. B Mater. Biol. Med., 2015, 3, 6605-6617.
[http://dx.doi.org/10.1039/C5TB00900F]
[38]
Agudelo, D.; Bérubé, G.; Tajmir-Riahi, H.A. An overview on the delivery of antitumor drug doxorubicin by carrier proteins. Int. J. Biol. Macromol., 2016, 88, 354-360.
[http://dx.doi.org/10.1016/j.ijbiomac.2016.03.060] [PMID: 27037051]
[39]
Dai, L.; Li, C-X.; Liu, K-F.; Su, H-J.; Chen, B-Q.; Zhang, G-F.; He, J.; Lei, J-D. Self-assembled serum albumin-poly(L-lactic acid) nanoparticles: novel nanoparticle platform for drug delivery in cancer. RSC Advances, 2015, 5, 15612-15620.
[http://dx.doi.org/10.1039/C4RA16346J]
[40]
Zheng, G.; Glickson, J.D. Lipoprotein-based nanoplatforms U.S. Patent 2008/0253960, 2008.
[41]
Zheng, G.; Chance, B.; Glickson, J.D. Lipoprotein nanoplatforms Int. Pat. Appl. 2006. 2006/073419,
[42]
Zheng, G.; Zhang, Z.; Corbin, I.; Chen, J. High-density lipoprotein-like peptide-phospholipid scaffold (“HPPS”) nanoparticles Int. Pat. Appl. 2009/073984, 2009.
[43]
Farokhzad, O.C.; Kolishetti, N.; Dhar, S.; Lippard, S.; Langer, R.S. Particles for multiple agent delivery Int. Pat.Appl. 2011/084620 2011.
[44]
Dewitt, D.M. High throughput fabrication of nanoparticles Int. Pat. Appl. 2010/030763, 2010.
[45]
Horres, R.; Hoffmann, M.; Faust, V.; Hoffmann, E.; Di Biase, D. Biocampatible, biostable coating of medical surfaces Int. Pat. Appl. 2005/032611, 2005.
[46]
Dai, L.; Dan, L.; Cheng, J.; Liu, J.; Deng, L-H.; Wang, L-Y.; Lei, J-D.; He, J. Water soluble multiarm-polyethylene glycol-betulinic acid prodrugs: design, synthesis, and in vivo effectiveness. Polym. Chem., 2014, 5, 5775-5783.
[http://dx.doi.org/10.1039/C4PY00648H]
[47]
Dash, S.K.; Dash, S.S.; Chattopadhyay, S.; Ghosh, T.; Tripathy, S.; Mahapatra, S.K.; Bag, G.B.; Das, D.; Roy, S. Folate decorated delivery of self assembled betulinic acid nano fibers: a biocompatible anti-leukemic therapy. RSC Advances, 2015, 5, 24144-24157.
[http://dx.doi.org/10.1039/C5RA01076D]
[48]
Dai, L.; Cao, X.; Liu, K-F.; Li, C-X.; Zhang, G-F.; Deng, L-H.; Si, C-L.; He, J.; Lei, J-D. Self-assembled targeted folate-conjugated eight-arm polyethylene glycol-betulinic acid nanoparticles for co-delivery of anticancer drugs. J. Mater. Chem. B Mater. Biol. Med., 2015, 3, 3754-3766.
[http://dx.doi.org/10.1039/C5TB00042D]
[49]
Vajtai, R. Springer Handbook of Nanomaterials. Heidelberg, S.B., Ed.; R. Vajtai; ,. , 2013.
[50]
Chung, B.Y.; Bang, S.S.; Yoo, M.J.; Bae, G.W.; Jeong, M.W.; Jeong, I.W. Anticancer composition for oral administration,containing pegylated botulin derivative. Int. Pat.Appl. 2015/080396, 2015.
[51]
Lomkova, E.A.; Chytil, P.; Janoušková, O.; Mueller, T.; Lucas, H.; Filippov, S.K.; Trhlíková, O.; Aleshunin, P.A.; Skorik, Y.A.; Ulbrich, K.; Etrych, T. Biodegradable micellar HPMA-based polymer-drug conjugates with betulinic acid for passive drug targeting. Biomacromolecules, 2016, 17(11), 3493-3507.
[http://dx.doi.org/10.1021/acs.biomac.6b00947] [PMID: 27636143 ]
[52]
Lyu, H.; Zheng, L.; Zhang, Z.; Zhou, J. Polyethylene glycol vitamin E succinate and calprotectin modified nanoparticle and preparation method thereof CN Patent 103735514, 2014.
[53]
Navin, V.; Rajesh, S.K.; Sunil, S.; Vinod, K.G. Novel dosage form U.S. Patent 2006/0024365, 2006.
[54]
Watterson, A.C.; Danprasert, K.; Diwan, A. Novel amphiphilic polymeric materials U.S. Patent 2002/0099164 2002.
[55]
Rapoport, N.; Gao, Z. Echogenic microbubbles and microemulsions for ultrasound-enhanced nanoparticle-mediated delivery of agents U.S. Patent 2009/0117177 2009.
[56]
Rapoport, N.; Gao, Z. Echogenic microbubbles and microemulsions for ultrasound-enhanced nanoparticle-mediated delivery of agents Int. Pat. Appl. 2006/127953 2006.
[57]
Khattar, D.; Kumar, M.; Garg, M.; Mukherjee, R.; Burman, A.C.; Jaggi, M.; Singh, A.T.; Awasthi, A. Proliposomal and liposomal compositions Int. Pat. Appl. 2008/114274, 2008.
[58]
Alkan-Onyuksel, H.; Rubinstein, I. Materials and methods for making improved micelle compositions Int. Pat. Appl.00/44348, 2000.
[59]
Dash, S.K.; Chattopadhyay, S.; Dash, S.S.; Tripathy, S.; Das, B.; Mahapatra, S.K.; Bag, B.G.; Karmakar, P.; Roy, S. Self assembled nano fibers of betulinic acid: A selective inducer for ROS/TNF-alpha pathway mediated leukemic cell death. Bioorg. Chem., 2015, 63, 85-100.
[http://dx.doi.org/10.1016/j.bioorg.2015.09.006] [PMID: 26469741 ]
[60]
Dash, S.K.; Chattopadhyay, S.; Ghosh, T.; Dash, S.S.; Tripathy, S.; Das, B.; Bag, B.G.; Das, D.; Roy, S. Self-assembled betulinic acid protects doxorubicin induced apoptosis followed by reduction of ROS-TNF-α-caspase-3 activity. Biomed. Pharmacother., 2015, 72, 144-157.
[http://dx.doi.org/10.1016/j.biopha.2015.04.017] [PMID: 26054689 ]
[61]
Dai, L.; Liu, K.; Si, C.; Wang, L.; Liu, J.; He, J.; Lei, J. Ginsenoide nanoparticle: a new green drug delivery system. J. Mater. Chem. B Mater. Biol. Med., 2016, 4, 529-538.
[http://dx.doi.org/10.1039/C5TB02305J]
[62]
Castor, T.P. Phospholipid nanosomes. Curr. Drug Deliv., 2005, 2(4), 329-340.
[http://dx.doi.org/10.2174/156720105774370195] [PMID: 16305436 ]
[63]
Mullauer, F.B.; van Bloois, L.; Daalhuisen, J.B.; Ten Brink, M.S.; Storm, G.; Medema, J.P.; Schiffelers, R.M.; Kessler, J.H. Betulinic acid delivered in liposomes reduces growth of human lung and colon cancers in mice without causing systemic toxicity. Anticancer Drugs, 2011, 22(3), 223-233.
[http://dx.doi.org/10.1097/CAD.0b013e3283421035] [PMID: 21263311]
[64]
Yihui, D.; Xiaohui, D.; Li, S.; Yi, L.; Ruiqi, W.; Que, W.; Jia, Z.; Ling, Z.; Weiwei, H.; Yang, S.; Huan, X.; Long, W. Drug delivery system and preparation method thereof CN Patent 101485629, 2009.
[65]
Einbond, L.S.; Redenti, S. Methods and compositions for the treatment of cancer U.S. Patent 2013/0315983,
[66]
Shen, J. Preparation method for betulinic acid liposomes CN Patent, 103622910, 2014.
[67]
Yu, L.; Chunhua, Y.; Yan, Q.; Jinghan, L.; Bocheng, Z.; Changluo, Z.; Lianghong, S.; Dachao, H. Antineoplastic traditional Chinese medicine preparation and preparation method thereof CN Patent 101342179, 2009.
[68]
Dehelean, C.A.; Feflea, S.; Ganta, S.; Amiji, M. Anti-angiogenic effects of betulinic acid administered in nanoemulsion formulation using chorioallantoic membrane assay. J. Biomed. Nanotechnol., 2011, 7(2), 317-324.
[http://dx.doi.org/10.1166/jbn.2011.1297] [PMID: 21702370 ]
[69]
Ciurlea, S.A.; Dehelean, C.A.; Ionescu, D.; Berko, S.; Csanyi, E.; Hadaruga, D.I.; Ganta, S.; Amiji, M.M. A comparative study regarding melanoma activity of betulinic acid on topical ointment vs. systematic nanoemulsion delivery systems. J. Agroaliment. Processes Technol, 2010, 16(4), 420-426.
[70]
Dehelean, C.A.; Feflea, S.; Gheorgheosu, D.; Ganta, S.; Cimpean, A.M.; Muntean, D.; Amiji, M.M. Anti-angiogenic and anti-cancer evaluation of betulin nanoemulsion in chicken chorioallantoic membrane and skin carcinoma in Balb/c mice. J. Biomed. Nanotechnol., 2013, 9(4), 577-589.
[http://dx.doi.org/10.1166/jbn.2013.1563] [PMID: 23621016]
[71]
Wang, G.; Yang, M.; Ye, W.; Xiang, J.; Cao, G.; Xu, Y.; Wang, S. Anti-cancer medicine 23-hydroxy betulic acid fat emulsion and its preparing method CN Patent 1682741, 2005.
[72]
Eugster, C.; Eugster, C.H. Ultramicro-emulsions of spontaneously dispersible concentrates containing antitumorally, antivarally and antiparasitically active esters of pentacyclic triterpenes Int. Pat. Appl 98/32443, 1998.
[73]
Kipp, J.E.; Doty, M.J.; Rebbeck, C.L. Dispersions prepared by use of self-stabilizing agents U.S. Patent 2005/0196416, 2005.
[74]
Kipp, J.E.; Doty, M.; Rebbeck, C.L. Dispersions prepared by use of self-stabilizing agents. Int. Pat. Appl. 2005/077337, 2005.
[75]
Rapoport, N. Stable nanoemulsions useful in the treatment of cancer U.S. Patent 2014/0341803, 2014.
[76]
Gorbunova, M.N.; Krainova, G.F.; Kisel’kov, D.M.; Nebogatikov, V.O. Copolymers of betulin esters and silver nanocomposites based on them. Russ. J. Appl. Chem., 2016, 89(3), 439-446.
[http://dx.doi.org/10.1134/S1070427216030149]
[77]
Kuznetsova, S.A.; Shakhtshneider, T.P.; Mikhailenko, M.A.; Malyar, Yu.N.; Spivak, E.A.; Zamai, T.N.; Zamai, A.S.; Chesnokov, N.V.; Kuznetsov, B.N.; Boldyrev, V.V. Antitumor activity of the diacylated betulin composites with arabinogalactan. Dokl. Chem., 2014, 459(Part 1), 199-201.
[http://dx.doi.org/10.1134/S0012500814110019]
[78]
Shakhtshneider, T.P.; Kuznetsova, S.A.; Mikhailenko, M.A.; Zamai, A.S.; Malyar, Yu.N.; Zamai, T.N.; Boldyrev, V.V. Effect of mechanochemical treatment on physicochemical and antitumor properties of betulin diacetate mixtures with arabinogalactan. Chem. Nat. Compd., 2013, 49, 470-474.
[http://dx.doi.org/10.1007/s10600-013-0641-x]
[79]
Kuznetsova, S.A.; Shakhtshnejder, T.P.; Mikhajlenko, M.A.; Maljar, J.N.; Zamaj, A.S.; Boldyrev, V.V. betulin diacetate-based composition RU Patent 2517157, 2014.
[80]
Shakhtshneider, T.P.; Kuznetsova, S.A.; Zamay, A.S.; Zamay, T.N.; Spivak, E.A.; Mikhailenko, M.A.; Malyar, Y.N.; Kuznetsov, B.N.; Chesnokov, N.V.; Boldyrev, V.V. New composites of betulin esters with arabinogalactan as highly potent anti-cancer agents. Nat. Prod. Res., 2016, 30(12), 1382-1387.
[http://dx.doi.org/10.1080/14786419.2015.1060591] [PMID: 26165861 ]
[81]
Kuznetsova, S.A.; Shakhtshnejder, T.P.; Mikhajlenko, M.A.; Maljar, J.N.; Boldyrev, V.V. Dipropionate betulin composition RU Patent 2541153, 2015.
[82]
Krukiewicz, K.; Bednarczyk-Cwynar, B.; Turczyn, R.; Zak, K.J. EQCM verification of the concept of drug immobilization and release from conducting polymer matrix. Electrochim. Acta, 2016, 212, 694-700.
[http://dx.doi.org/10.1016/j.electacta.2016.07.055]
[83]
Krukiewicz, K.; Cichy, M.; Ruszkowski, P.; Turczyn, R.; Jarosz, T.; Zak, J.K.; Lapkowski, M.; Bednarczyk-Cwynar, B. Betulin-loaded PEDOT films for regional chemotherapy. Mater. Sci. Eng. C, 2017, 73, 611-615.
[http://dx.doi.org/10.1016/j.msec.2016.12.115] [PMID: 28183652]
[84]
Yadav, R.; Kumar, D.; Kumari, A.; Yadav, S.K. PLA nanovectors with encapsulated betulin: plant leaf extract-synthesized nanovectors are more efficacious than PVA-synthesized nanovectors. Biotechnol. Lett., 2016, 38(2), 259-269.
[http://dx.doi.org/10.1007/s10529-015-1981-3] [PMID: 26476528 ]
[85]
Bomshteyn, A.L.; Ratham, P. Betulinol derivatives Int. Pat.Appl. 98/55497, 1998.
[86]
Bag, B.G.; Dash, S.S. Hierarchical self-assembly of a renewable nanosized pentacyclic dihydroxy-triterpenoid betulin yielding flower-like architectures. Langmuir, 2015, 31(51), 13664-13672.
[http://dx.doi.org/10.1021/acs.langmuir.5b03730] [PMID: 26671722]
[87]
Hao, H.; Hongbin, S.; Yingxia, Z. Pentacyclic triterpene and melbine salt of derivative thereof, preparation method and medical application of pentacyclic triterpene CN Patent 101704874, 2010.
[88]
Kim, S.M.; Chae, M.K.; Yim, M.S.; Jeong, I.H.; Cho, J.; Lee, C.; Ryu, E.K. Hybrid PET/MR imaging of tumors using an oleanolic acid-conjugated nanoparticle. Biomaterials, 2013, 34(33), 8114-8121.
[http://dx.doi.org/10.1016/j.biomaterials.2013.07.078] [PMID: 23932293]
[89]
Ren, Y.; Liu, Y.; Niu, R.; Liao, X.; Zhang, J.; Yang, B. Host-guest inclusion system of oleanolic acid with methyl-β-cyclodextrin: prearation, characterization and anticancer activity. J. Mol. Struct., 2016, 1117, 1-7.
[http://dx.doi.org/10.1016/j.molstruc.2016.03.071]
[90]
Zhang, J.; Gao, Y.; Su, F.; Gong, Z.; Zhang, Y. Interaction characteristics with bovine serum albumin and retarded nitric oxide release of ZCVI4-2, a new nitric oxide-releasing derivative of oleanolic acid. Chem. Pharm. Bull. (Tokyo), 2011, 59(6), 734-741.
[http://dx.doi.org/10.1248/cpb.59.734] [PMID: 21628910]
[91]
Zhou, J.; Huo, M.; Wang, J.; Zhang, X.; Wang, L.; Yin, T. Amphiphilic polysaccharide-anti-tumor medicament conjugate capable of releasing medicines specifically at lesion site of living body, as well as preparation method and application of medicinal composition of amphiphilic polysaccharide-anti-tumor medicament conjugate CN Patent 103301472 2013.
[92]
Yao, J.; Li, Y.; Zhou, J. Preparation and anti-tumor application of natural active drug-polysaccharide targeted compound CN Patent 103705940, 2014.
[93]
Gao, M.; Xu, H.; Bao, X.; Zhang, C.; Guan, X.; Liu, H.; Lv, L.; Deng, S.; Gao, D.; Wang, C.; Tian, Y. Oleanolic acid-loaded PLGA-TPGS nanoparticles combined with heparin sodium-loaded PLGA-TPGS nanoparticles for enhancing chemotherapy to liver cancer. Life Sci., 2016, 165, 63-74.
[http://dx.doi.org/10.1016/j.lfs.2016.09.008] [PMID: 27640889 ]
[94]
Man, D.K.W.; Casettari, L.; Cespi, M.; Bonacucina, G.; Palmieri, G.F.; Sze, S.C.W.; Leung, G.P.H.; Lam, J.K.W.; Kwok, P.C.L. Oleanolic acid loaded PEGylated PLA and PLGA nanoparticles with enhanced cytotoxic activity against cancer cells. Mol. Pharm., 2015, 12(6), 2112-2125.
[http://dx.doi.org/10.1021/acs.molpharmaceut.5b00085] [PMID: 25881668 ]
[95]
Zhao, Y.; Huo, M.; Xu, Z.; Wang, Y.; Huang, L. Nanoparticle delivery of CDDO-Me remodels the tumor microenvironment and enhances vaccine therapy for melanoma. Biomaterials, 2015, 68, 54-66.
[http://dx.doi.org/10.1016/j.biomaterials.2015.07.053] [PMID: 26264646 ]
[96]
Bao, X.; Gao, M.; Xu, H.; Liu, K.X.; Zhang, C.H.; Jiang, N.; Chu, Q.C.; Guan, X.; Tian, Y. A novel oleanolic acid-loaded PLGA-TPGS nanoparticle for liver cancer treatment. Drug Dev. Ind. Pharm., 2015, 41(7), 1193-1203.
[http://dx.doi.org/10.3109/03639045.2014.938081] [PMID: 25026246]
[97]
Gu, X.; Qiu, Z.; Xu, H.; Bao, X.; Gao, M.; Mei, L.; Tian, Y. Optimization of preparation technology of oleanolic acid-loaded PCL-PLA-TPGS nanoparticles and in vitro cell inhibitory test. China Pharmacy, 2012, 23(37), 3497-3499.
[98]
Gao, D.; Tang, S.; Tong, Q. Oleanolic acid liposomes with polyethylene glycol modification: promising antitumor drug delivery. Int. J. Nanomedicine, 2012, 7, 3517-3526.
[http://dx.doi.org/10.2147/IJN.S31725] [PMID: 22848175 ]
[99]
Tang, S.; Gao, D.; Zhao, T.; Zhou, J.; Zhao, X. An evaluation of the anti-tumor efficacy of oleanolic acid-loaded PEGylated liposomes. Nanotechnology, 2013, 24(23)235102
[http://dx.doi.org/10.1088/0957-4484/24/23/235102] [PMID: 23670283]
[100]
Bian, Y.; Gao, D.; Liu, Y.; Li, N.; Zhang, X.; Zheng, R.Y.; Wang, Q.; Luo, L.; Dai, K. Preparation and study on anti-tumor effect of chitosan-coated oleanolic acid liposomes. RSC Advances, 2015, 5, 18725-18732.
[http://dx.doi.org/10.1039/C4RA13860K]
[101]
Luo, L.; Bian, Y.; Liu, Y.; Zhang, X.; Wang, M.; Xing, S.; Li, L.; Gao, D. Combined near infrared photothermal therapy and chemotherapy using gold nanoshells coated liposomes to enhance antitumor effect. Small, 2016, 12(30), 4103-4112.
[http://dx.doi.org/10.1002/smll.201503961] [PMID: 27294601 ]
[102]
Gao, D.; Bian, Y.; Liu, Y.; Zhang, X.; Li, N.; Ji, B. Oleanolic acid liposome coated with nanogold spherical shell and preparation method thereof CN Patent 104984339, 2015.
[103]
Li, W.; Ng, K.Y.; Heng, P.W.S. Development and evaluation of optimized sucrose ester stabilized oleanolic acid nanosuspensions prepared by wet ball milling with design of experiments. Biol. Pharm. Bull., 2014, 37(6), 926-937.
[http://dx.doi.org/10.1248/bpb.b13-00864] [PMID: 24882406 ]
[104]
Li, W.; Das, S.; Ng, K.Y.; Heng, P.W.S. Formulation, biological and pharmacokinetic studies of sucrose ester-stabilized nanosuspensions of oleanolic Acid. Pharm. Res., 2011, 28(8), 2020-2033.
[http://dx.doi.org/10.1007/s11095-011-0428-3] [PMID: 21479757 ]
[105]
Minda, D.; Pavel, I.Z.; Borcan, F.; Coricovac, D.; Pinzaru, I.; Andrica, F.; Morgovan, C.; Nita, L.D.; Soica, C.; Muntean, D.; Toma, C.C. Beneficial effects of a lupeol-cyclodextrin complex in a murine model of photochemical skin carcinoma. Rev. Chim, 2015, 66, 373-377.
[106]
Gupta, R.C.; Vadhanam, M.V.; Aqil, F. Methods and compositions for controlled delivery of phytochemical agents.Int. Pat. Appl. 2013/148682, 2013.
[107]
Gupta, R.C.; Vadhanam, M.V. Methods and compositions for controlled delivery of phytochemical agents. Int. Pat.Appl. 2009/114525, 2009.
[108]
Arunachalam, V.M.; John, J.; Gnanou, Y.M.D.; Kari, V. Dendrimers, conjugates and methods thereof Int. Pat. Apl.2014/041517, 2014.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 27
ISSUE: 8
Year: 2020
Page: [1308 - 1336]
Pages: 29
DOI: 10.2174/0929867325666180530095657
Price: $65

Article Metrics

PDF: 24
HTML: 4