Abstract
In this study, the formation of supramolecular inclusion complex of doxorubicin (DOX), a high loading and pH-dependent delivery of DOX on β-CD dendrimer was studied. β-cyclodextrin (β-CD) dendrimer having β-CD in both periphery and core was prepared with entrapment efficiency using click reaction. The encapsulation property of the β-CD-dendrimer was investigated by DOX as model drug. The chemical construction of β-CD-dendrimer was described by 1H NMR, 13C NMR and FTIR and its inclusion complex construction was studied by FTIR, DSC, SEM, and DLS techniques. It was confirmed that β-CD dendrimer able to encapsulate DOX in solution; as a result, the designed complex revealed pH-dependent sustained release of DOX, in vitro. Also, the in vitro outcomes on T47D cells displayed that complexation of DOX with β-CD dendrimer involved an improvement of in vitro cytotoxicity and anticancer activity and this data appeared to be as a result of the developed solubility of the DOX.
Similar content being viewed by others
References
Tomalia, D.A., Baker, H., Dewald, J.R., Hall, M., Kallos, G., Martin, S., Roeck, J., Ryder, J., Smith, P.: A new class of polymers: starburst-dendritic macromolecules. Polym. J. 17(1), 117–132 (1985)
Namazi, H., Adeli, M.: Novel linear–globular thermoreversible hydrogel ABA type copolymers from dendritic citric acid as the A blocks and poly(ethyleneglycol) as the B block. Eur. Polym. J. 39(7), 1491–1500 (2003)
Namazi, H., Toomari, Y., Abbaspour, H.: Fabrication of triblock ABA type peptide dendrimer based on glutamic acid dimethyl ester and PEG as a potential nano drug delivery agent. BI. 4(4), 175–182 (2014)
Namazi, H., Didehban, K., Entezami, A.A.: Dendrimer-based hydrogen-bonded liquid crystalline complexes: Synthesis and characterization. Eur. Polym. J. 45(6), 1836–1844 (2009)
Namazi, H., Jafarirad, S.: Application of Hybrid Organic/Inorganic Dendritic ABA Type Triblock Copolymers as New Nanocarriers in Drug Delivery Systems. Int. J. Polymer. Mater. 60(9), 603–619 (2011)
Jolly, A.M., Bonizzoni, M.: PAMAM dendrimers as supramolecular hosts through non-covalent interactions. Supramol. Chem. 27(3), 151–160 (2014)
Huang, Y., Kang, Q.: Synthesis of conjugates of β-cyclodextrin with polyamidoamine dendrimers and their molecular inclusion interaction with levofloxacin lactate. J. Incl. Phenom. Macro. 72(1), 55–61 (2011)
Tomalia, D.A., Fréchet, J.M.J.: Discovery of dendrimers and dendritic polymers: A brief historical perspective. J. Polym. Sci. Part A Polym. Chem. 40(16), 2719–2728 (2002)
Namazi, H., Toomari, Y.: Novel pH Sensitive Nanocarrier Agents Based on Citric Acid Dendrimers Containing Conjugated β-Cyclodextrins. Adv. Pharm. Bull. 1(1), 40–47 (2011)
Leng, Z.H., Zhuang, Q.F., Li, Y.C., He, Z., Chen, Z., Huang, S.P., Jia, H.Y., Zhou, J.W., Liu, Y., Du, L.B.: Polyamidoamine dendrimer conjugated chitosan nanoparticles for the delivery of methotrexate. Carbohydr. Polym. 98(1), 1173–1178 (2013)
Namazi, H., Adeli, M.: Dendrimers of citric acid and poly (ethylene glycol) as the new drug-delivery agents. Biomaterials. 26(10), 1175–1183 (2005)
Jędrych, M., Borowska, K., Galus, R., Jodłowska-Jędrych, B.: The evaluation of the biomedical effectiveness of poly(amido)amine dendrimers generation 4.0 as a drug and as drug carriers: a systematic review and meta-analysis. Int. J. Pharm. 462(1–2), 38–43 (2014)
Fernandez, L., Gonzalez, M., Cerecetto, H., Santo, M., Silber, J.J.: Solubilization and release properties of dendrimers. evaluation as prospective drug delivery systems. Supramol. Chem. 18(8), 633–643 (2006)
Ortiz Mellet, C., Defaye, J., Garcia Fernandez, J.M.: Multivalent cyclooligosaccharides: versatile carbohydrate clusters with dual role as molecular receptors and lectin ligands. Chemistry (Weinheim an der Bergstrasse, Germany). 8(9), 1982–1990 (2002)
Ritter, H., Tabatabai, M.: Cyclodextrin in polymer synthesis: a green way to polymers. Prog. Polym. Sci. 27(9), 1713–1720 (2002)
Zhao, F., Yin, H., Zhang, Z., Li, J.: Folic acid modified cationic gamma-cyclodextrin-oligoethylenimine star polymer with bioreducible disulfide linker for efficient targeted gene delivery. Biomacromolecules. 14(2), 476–484 (2013)
Wen, Y., Zhang, Z., Li, J.: Highly efficient multifunctional supramolecular gene carrier system self-assembled from redox-sensitive and Zwitterionic polymer blocks. Adv. Funct. Mater. 24(25), 3874–3884 (2014)
Zhang, Z.-X., Liu, K.L., Li, J.: A thermoresponsive hydrogel formed from a star–star supramolecular architecture. Angew. Chem. Int. Ed. 52(24), 6180–6184 (2013)
Hawker, C.J., Bosman, A.W., Harth, E.: New polymer synthesis by nitroxide mediated living radical polymerizations. Chem. Rev. 101(12), 3661–3688 (2001)
Saenger, W.R., Jacob, J., Gessler, K., Steiner, T., Hoffmann, D., Sanbe, H., Koizumi, K., Smith, S.M., Takaha, T.: Structures of the common cyclodextrins and their larger analogues-beyond the doughnut. Chem. Rev. 98(5), 1787–1802 (1998)
Namazi, H., Kanani, A.: Synthesis of new prodrugs based on beta-CD as the natural compounds containing beta-lactam antibiotics. J. Bioact. Compat. Pol. 22(1), 77–88 (2007)
Namazi, H., Kanani, A.: Investigation diffusion mechanism of beta-lactam conjugated telechelic polymers of PEG and beta-cyclodextrin as the new nanosized drug carrier devices. Carbohydr. Polym. 76(1), 46–50 (2009)
Uekama, K., Hirayama, F., Irie, T.: Cyclodextrin drug carrier systems. Chem. Rev. 98(5), 2045–2076 (1998)
Zhang, Z.-X., Liu, K.L., Li, J.: Self-assembly and micellization of a dual thermoresponsive supramolecular pseudo-block copolymer. Macromolecules. 44(5), 1182–1193 (2011)
Toda, M., Kondo, Y., Hamada, F.: Supramolecular assembly system depended on guest species based on bis-naphthane modified β-cyclodextrin dimer. J. Incl. Phenom. Macro. 59(3), 341–344 (2007)
Zhao, D., Liao, K., Ma, X., Yan, X.: Study of the supramolecular inclusion of β-cyclodextrin with andrographolide. J. Incl. Phenom. Macro. 43(3), 259–264 (2002)
Prabu, S., Sivakumar, K., Swaminathan, M., Rajamohan, R.: Preparation and characterization of host–guest system between inosine and β-cyclodextrin through inclusion mode. Spectrochim. Acta Mol. Biomol. Spectrosc. 147, 151–157 (2015)
Del Valle, E.M.M.: Cyclodextrins and their uses: a review. Process Biochem. 39(9), 1033–1046 (2004)
Li, J., Loh, X.J.: Cyclodextrin-based supramolecular architectures: syntheses, structures, and applications for drug and gene delivery. Adv. Drug Deliv. Rev. 60(9), 1000–1017 (2008)
Menuel, S., Fontanay, S., Clarot, I., Duval, R.E., Diez, L., Marsura, A.: Synthesis and complexation ability of a novel bis-(guanidinium)-tetrakis-(beta-cyclodextrin) dendrimeric tetrapod as a potential gene delivery (DNA and siRNA) system. Study of cellular siRNA transfection. Bioconjug. Chem. 19(12), 2357–2362 (2008)
Benito, J.M., Gómez-García, M., Ortiz Mellet, C., Baussanne, I., Defaye, J., García Fernández, J.M.: Optimizing saccharide-directed molecular delivery to biological receptors: design, synthesis, and biological evaluation of glycodendrimer–cyclodextrin conjugates. J. Am. Chem. Soc. 126(33), 10355–10363 (2004)
Cheng, Y., Zhao, L., Li, Y., Xu, T.: Design of biocompatible dendrimers for cancer diagnosis and therapy: current status and future perspectives. Chem. Soc. Rev. 40(5), 2673–2703 (2011)
Singal, P.K., Iliskovic, N., Li, T., Kumar, D.: Adriamycin cardiomyopathy: pathophysiology and prevention. FASEB J. 11(12), 931–936 (1997)
Kalaria, D.R., Sharma, G., Beniwal, V., Ravi Kumar, M.N.: Design of biodegradable nanoparticles for oral delivery of doxorubicin: in vivo pharmacokinetics and toxicity studies in rats. Pharm. Res. 26(3), 492–501 (2009)
Janes, K.A., Fresneau, M.P., Marazuela, A., Fabra, A., Alonso, M.J.: Chitosan nanoparticles as delivery systems for doxorubicin. J. Control. Release. 73(2–3), 255–267 (2001)
Toomari, Y., Namazi, H., Entezami, A.A.: Synthesis of the dendritic type β-cyclodextrin on primary face via click reaction applicable as drug nanocarrier. Carbohydr. Polym. 132(0), 205–213 (2015)
Wu, W., Wang, Y., Que, L.: Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system. Eur. J. Pharm. Biopharm. 63(3), 288–294 (2006)
Giordano, F., Novak, C., Moyano, J.R.: Thermal analysis of cyclodextrins and their inclusion compounds. Thermochim. Acta. 380(2), 123–151 (2001)
Stojanov, M., Larsen, K.L.: Cetirizine release from cyclodextrin formulated compressed chewing gum. Drug Dev. Ind. Pharm. 38(9), 1061–1067 (2012)
Acknowledgements
Authors gratefully acknowledge the financial support from the University of Tabriz and RCPN of Tabriz University of Medical Science.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yousef, T., Hassan, N. Supramolecular encapsulation of doxorubicin with β-cyclodextrin dendrimer: in vitro evaluation of controlled release and cytotoxicity. J Incl Phenom Macrocycl Chem 87, 105–115 (2017). https://doi.org/10.1007/s10847-016-0682-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10847-016-0682-4