In this work, molecularly imprinted nanospheres for controlled/sustained release of quercetin were synthesized employing methacrylic acid and ethylene glycoldymethacrylate as functional monomer and crosslinking agent, respectively. One pot precipitation polymerization was chosen as polymerization technique to obtain nanosized materials with spherical shape. Morphological and hydrophilic properties by scanning electron microscopy and water content measurements were determined, and recognition and selectivity properties of the imprinted materials were tested using the template quercetin and its structural analogue, the flavonoid catechin. Finally, the applicability of the obtained materials as drug delivery devices was evaluated by performing in vitro release studies in plasma simulating fluids and cytotoxicity testson HeLa cells.
References
[1]
Couvreur, P.; Vauthier, C. Nanotechnology: Intelligent design to treat complex disease. Pharm. Res. 2007, 23, 1417–1450, doi:10.1007/s11095-006-0284-8.
[2]
Torchilin, V.P. Targeted pharmaceutical nanocarriers for cancer therapy and imaging. AAPS J. 2007, 9, 128–147, doi:10.1208/aapsj0902015.
[3]
Maeda, H.; Wu, J.; Sawa, T.; Matsumura, Y.; Hori, K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: A review. J. Control. Release 2000, 65, 271–284, doi:10.1016/S0168-3659(99)00248-5.
[4]
Chinsriwongkul, A.; Chareanputtakhun, P.; Ngawhirunpat, T.; Rojanarata, T.; Sila-On, W.; Rutkanonkai, U.; Opanasopit, P. Nanostructured Lipid Carriers (NLC) for parenteral delivery of ananticancer drug. AAPS PharmSciTech 2012, 13, 150–158, doi:10.1208/s12249-011-9733-8.
[5]
Chauhan, A.S.; Jain, N.K.; Diwan, P.V.; Khopade, A.J. Solubility enhancement of indomethacin with withpoly(amidoamine) dendrimersand targeting to inflammatory regions of arthritic rats. J. Drug Target. 2004, 12, 9–10.
[6]
Byrne, M.E.; Salian, V. Molecular imprinting within hydrogels II: Progress and analysis of the field. Int. J. Pharm. 2004, 364, 188–212, doi:10.1016/j.ijpharm.2008.09.002.
Xie, C.; Liu, B.; Wang, Z.; Gao, D.; Guan, G.; Zhang, Z. Molecular imprinting at walls of silica nanotubes for TNT recognition. Anal. Chem. 2008, 80, 437–443, doi:10.1021/ac701767h.
[9]
Cirillo, G.; Iemma, F.; Puoci, F.; Parisi, O.I.; Curcio, M.; Spizzirri, U.G.; Picci, N. Imprinted hydrophilic nanospheres as drug delivery systems for 5-fluorouracil sustained release. J. Drug Target. 2009, 17, 72–77, doi:10.1080/10611860802455813.
[10]
Curcio, M.; Puoci, F.; Cirillo, G.; Iemma, F.; Spizzirri, U.G.; Picci, N. Selective determination of melamine in aqueous medium by molecularly imprinted solid phase extraction. J. Agric. Food Chem. 2010, 58, 11883–11887, doi:10.1021/jf102936p.
[11]
Vidyasankar, S.; Arnold, F.H. Molecular imprinting: selective materials for separations, sensors and catalysis. Curr. Opin. Biotechnol. 1995, 6, 218–224, doi:10.1016/0958-1669(95)80036-0.
Cunliffe, D.; Kirby, A.; Alexander, C. Molecularly imprinted drug delivery systems. Adv. Drug Deliv. Rev. 2005, 57, 1836–1853. 16226341
[16]
Sellergren, B.; Allender, C.J. Molecularly imprinted polymers: A bridge to advanced drug delivery. Adv. Drug Deliv. Rev. 2005, 57, 1733–1741, doi:10.1016/j.addr.2005.07.010.
[17]
Singh, B.; Chauhan, N.; Sharma, V. Design of molecular imprinted hydrogels for controlled release of cisplatin: Evaluation of network density of hydrogels. Ind. Eng. Chem. Res. 2011, 50, 13742–13751, doi:10.1021/ie200758b.
[18]
Alvarez-Lorenzo, C.; Ya?ez, F.; Barreiro-Iglesias, R.; Concheiro, A. Imprinted soft contact lenses as norfloxacin delivery systems. J. Control. Release 2006, 113, 236–244, doi:10.1016/j.jconrel.2006.05.003.
[19]
Ciardelli, G.; Cioni, B.; Cristallini, C.; Barbani, N.; Silvestri, D.; Giusti, P. Acrylic polymeric nanospheres for the release and recognition ofmolecules of clinical interest. Biosens. Bioelectron. 2004, 20, 1083–1090, doi:10.1016/j.bios.2004.06.028.
[20]
Esfandyari-Manesh, M.; Javanbakht, M.; Atyabi, F.; Mohammadi, A.; Mohammadi, S.; Akbari-Adergani, B.; Dinarvand, R. Dipyridamole recognition and controlled release by uniformly sized molecularly imprinted nanospheres. Mater. Sci. Eng. C 2011, 31, 1692–1699, doi:10.1016/j.msec.2011.07.019.
[21]
Adlercreutz, H.; Mousavi, Y.; Hockerstedt, K. Diet and breast cancer. Acta Oncol. 1992, 31, 175–181, doi:10.3109/02841869209088899.
[22]
Ferry, D.R.; Smith, A.; Malkhandi, J.; Fyfe, D.W.; Takats, P.G.; Anderson, D.; Baker, J.; Kerr, D.J. Phase I clinical trial of the flavonoid quercetin: Pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin. Cancer Res. 1996, 2, 659–668. 9816216
[23]
Moon, Y.J.; Wang, L.; DiCenzo, R.; Morris, M.E. Quercetin pharmacokinetics in humans. Biopharm. Drug Dispos. 2008, 29, 205–217, doi:10.1002/bdd.605.
[24]
Zheng, Y.; Haworth, I.S.; Zuo, Z.; Chow, M.S.S.; Chow, A.H.L. Physicochemical and structural characterization of quer-cetin-b-cyclodextrin complexes. J. Pharm. Sci. 2005, 94, 1079–1089, doi:10.1002/jps.20325.
[25]
Kumari, A.; Yadav, S.K.; Pakade, Y.B.; Singh, B.; Yadav, S.C. Development of biodegradable nanoparticles for delivery of quercetin. Colloids Surf. B 2010, 80, 184–192, doi:10.1016/j.colsurfb.2010.06.002.
[26]
Lee, D.H.; Sim, G.S.; Kim, J.H.; Lee, G.S.; Pyo, H.B.; Lee, B.C. Preparation and characterization of quercetin-loadedpolymethyl methacrylate microcapsules usinga polyol-in-oil-in-polyol emulsion solventevaporation method. J. Pharm. Pharmacol. 2007, 59, 1611–1620, doi:10.1211/jpp.59.12.0002. 18053322
[27]
Barreto, A.C.H.; Santiago, V.R.; Mazzetto, S.E.; Denardin, J.C.; Lavìn, R.; Mele, G.; Ribeiro, M.E.N.P.; Vieira, I.G.P.; Gonalves, T.; Ricardo, N.M.P.S.; Fechine, P.B.A. Magnetic nanoparticles for a new drug delivery systemto control quercetin releasing for cancer chemotherapy. J. Nanopart. Res. 2011, 13, 6545–6553, doi:10.1007/s11051-011-0559-9.
[28]
Flavin, K.; Resmini, M. Imprinted nanomaterials: A new class of synthetic receptors. Anal. Bioanal. Chem. 2009, 393, 437–444, doi:10.1007/s00216-008-2496-8.
Alvarez-Lorenzo, C.; Concheiro, A. Molecularly imprinted polymers for drug delivery. J. Chromatogr. B 2004, 804, 231–245, doi:10.1016/j.jchromb.2003.12.032.
[31]
Ye, L.; Mosbach, K. Molecular imprinting: Synthetic materials as substitutes for biological antibodies and receptors. Chem. Mater. 2008, 20, 859–868, doi:10.1021/cm703190w.
[32]
Boos, K.S.; Fleischer, C.T. Multidimensional on-line solid-phase extraction (SPE) using restricted access materials (RAM) in combination with molecular imprinted polymers (MIP). J. Anal. Chem. 2001, 371, 16–20, doi:10.1007/s002160100831.
[33]
Gore, M.A.; Karmalkar, R.N.; Kulkarni, M.G. Enhanced capacities and selectivities for cholesterol in aqueous media by molecular imprinting: Role of novel crosslinkers. J. Chromatogr. B 2004, 804, 211–221, doi:10.1016/j.jchromb.2003.12.028.
[34]
Pitarresi, G.; Pierro, P.; Giammona, G.; Iemma, F.; Muzzalupo, R.; Picci, N. Drug release from α,β-poly(N-2-hydroxyethyl)-dl-aspartamide-based microparticles. Biomaterials 2004, 25, 4333–4343, doi:10.1016/j.biomaterials.2003.11.015.
[35]
Puoci, F.; Cirillo, G.; Curcio, M.; Iemma, F.; Parisi, O.I.; Castiglione, M.; Picci, N. Molecularly imprinted polymers for α-tocopherol delivery. Drug Deliv. 2008, 15, 253–258, doi:10.1080/10717540802006724.
Liu, Y.; Nair, M.G. An efficient and economical MTT assay for determining the antioxidant activity of plant natural product extracts and pure compounds. J. Nat. Prod. 2010, 73, 1193–1195, doi:10.1021/np1000945.
[38]
Priyadarsini, R.V.; Murugan, R.S.; Maitreyi, S.; Ramalingam, K.; Karunagaran, D.; Nagini, S. The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition. Eur. J. Pharmacol. 2012, 649, 84–91.
[39]
Jagtap, S.; Meganathan, K.; Wagh, V.; Winkler, J.; Hescheler, J.; Sachinidis, A. Chemoprotective mechanism of the natural compounds, epigallocatechin-3-O-gallate, quercetin and curcumin against cancer and cardiovascular diseases. Curr. Med. Chem. 2009, 16, 1451–1462, doi:10.2174/092986709787909578.
[40]
AlaaEddeen, M.; Seufi, A.M.; Ibrahim, S.S.; Elmaghraby, T.K.; Hafez, E.E. Preventive effect of the flavonoid, quercetin, on hepatic cancer in rats via oxidant/antioxidant activity: Molecular and histological evidences. J. Exp. Clin. Cancer Res. 2009, 28, doi:10.1186/1756-9966-28-80.
[41]
Boly, R.; Gras, T.; Lamkami, T.; Guissou, P.; Serteyn, D.; Kiss, R.; Dubois, J. Quercetin inhibits a large panel of kinases implicated in cancer cell biology. Int. J. Oncol. 2011, 38, 833–842. 21206969
[42]
Estella-Hermoso de Mendoza, A.; Préat, V.; Mollinedo, F.; Blanco-Prieto, M.J. In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against glioma. J. Control. Release 2011, 156, 421–426, doi:10.1016/j.jconrel.2011.07.030.
[43]
Song, X.; Li, J.; Wang, J.; Chen, L. Quercetin molecularly imprinted polymers: Preparation, recognition characteristics and properties as sorbent for solid phase extraction. Talanta 2009, 80, 694–702, doi:10.1016/j.talanta.2009.07.051.