Molecularly imprinted hydrogels for sustained release of sunitinib in breast cancer therapy
Luca Scrivano
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Search for more papers by this authorCorresponding Author
Ortensia Ilaria Parisi
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Macrofarm s.r.l., c/o Department of Pharmacy, Health and Nutrition Sciences, University of Calabria, Rende, Italy
Correspondence
Francesco Puoci, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy.
Email: [email protected]
Ortensia Ilaria Parisi, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy.
Email: [email protected]
Search for more papers by this authorDomenico Iacopetta
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Search for more papers by this authorMariarosa Ruffo
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Macrofarm s.r.l., c/o Department of Pharmacy, Health and Nutrition Sciences, University of Calabria, Rende, Italy
Search for more papers by this authorJessica Ceramella
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Search for more papers by this authorMaria Stefania Sinicropi
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Search for more papers by this authorCorresponding Author
Francesco Puoci
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Macrofarm s.r.l., c/o Department of Pharmacy, Health and Nutrition Sciences, University of Calabria, Rende, Italy
Correspondence
Francesco Puoci, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy.
Email: [email protected]
Ortensia Ilaria Parisi, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy.
Email: [email protected]
Search for more papers by this authorLuca Scrivano
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Search for more papers by this authorCorresponding Author
Ortensia Ilaria Parisi
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Macrofarm s.r.l., c/o Department of Pharmacy, Health and Nutrition Sciences, University of Calabria, Rende, Italy
Correspondence
Francesco Puoci, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy.
Email: [email protected]
Ortensia Ilaria Parisi, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy.
Email: [email protected]
Search for more papers by this authorDomenico Iacopetta
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Search for more papers by this authorMariarosa Ruffo
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Macrofarm s.r.l., c/o Department of Pharmacy, Health and Nutrition Sciences, University of Calabria, Rende, Italy
Search for more papers by this authorJessica Ceramella
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Search for more papers by this authorMaria Stefania Sinicropi
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Search for more papers by this authorCorresponding Author
Francesco Puoci
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
Macrofarm s.r.l., c/o Department of Pharmacy, Health and Nutrition Sciences, University of Calabria, Rende, Italy
Correspondence
Francesco Puoci, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy.
Email: [email protected]
Ortensia Ilaria Parisi, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy.
Email: [email protected]
Search for more papers by this authorAbstract
The present work reports on the synthesis of a molecularly imprinted polymer (MIP) based on methacrylic acid and ethylene glycol dimethacrylate for sunitinib delivery. Sunitinib (SUT) is a tyrosine kinase inhibitor used in many cancer diseases. Like the majority of the anticancer drugs, SUT suffers of a low bioavailability, and at the same time, it is characterized by a narrow therapeutic window. In order to reduce drug systemic toxicity, we synthesized a MIP-based drug delivery system for SUT-controlled release. MIP was obtained by bulk polymerization through the so-called noncovalent approach. Rebinding experiments were performed to evaluate the success of the imprinting process and the ability of MIP to bind in a specific and selective fashion the template molecule. Resulting data showed that sunitinib rebinding percentage was 70%, while nonimprinted polymer (NIP) rebinding percentage was 46%. A not significant difference was observed between MIP and NIP in semaxanib binding experiments. Moreover, the drug release profiles were studied for both MIP and NIP. A sustained release was observed from sunitinib-loaded MIP during 24 hours, reaching 58% after 6 hours and 76% at the end-point. NIP, on the contrary, released almost 90% of the loaded drug within 6 hours. Furthermore, the drug carrier was tested in vitro against MCF-7 cells, in which the cytotoxic effect of sunitinib released from MIP reached the maximum after 72 hours, while NIP completed its effect within 48 hours. These results demonstrated that molecularly imprinted polymers are suitable systems for SUT release.
REFERENCES
- 1Tamai Y, Tanaka H, Nakanishi K. Molecular dynamics study of polymer-water interaction in hydrogels. 1. Hydrogen-bond structure. Macromolecules. 1996; 29(21): 6750-6760.
- 2Xinming L, Yingde C, Lloyd AW, et al. Polymeric hydrogels for novel contact lens-based ophthalmic drug delivery systems: a review. Cont Lens Anterior Eye. 2008; 31(2): 57-64.
- 3Cormack PA, Elorza AZ. Molecularly imprinted polymers: synthesis and characterisation. J Chromatogr B. 2004; 804(1): 173-182.
- 4Mayes A, Whitcombe M. Synthetic strategies for the generation of molecularly imprinted organic polymers. Adv Drug Deliv Rev. 2005; 57(12): 1742-1778.
- 5Curcio M, Puoci F, Spizzirri UG, et al. Negative thermo-responsive microspheres based on hydrolyzed gelatin as drug delivery device. AAPS PharmSciTech. 2010; 11(2): 652-662.
- 6Gemeinhart RA, Chen J, Park H, Park K. pH-sensitivity of fast responsive superporous hydrogels. J Biomater Sci Polym Ed. 2000; 11(12): 1371-1380.
- 7Ahmed EM. Hydrogel: preparation, characterization, and applications: a review. J Adv Res. 2015; 6(2): 105-121.
- 8 Panel CIRE. Final report of the safety assessment of methacrylic acid. Int J Toxicol. 2005; 24: 33.
- 9Lally S, Mackenzie P, LeMaitre CL, Freemont TJ, Saunders BR. Microgel particles containing methacrylic acid: pH-triggered swelling behaviour and potential for biomaterial application. J Colloid Interface Sci. 2007; 316(2): 367-375.
- 10Leon A, Vincent B, Cawdery N. The synthesis and characterization of monodisperse poly (acrylic acid) and poly (methacrylic acid). Colloid Polym Sci. 1994; 272(4): 427-432.
- 11Parisi OI, Morelli C, Puoci F, et al. Magnetic molecularly imprinted polymers (MMIPs) for carbazole derivative release in targeted cancer therapy. J Mater Chem B. 2014; 2(38): 6619-6625.
- 12Puoci F, Cirillo G, Curcio M, et al. Molecularly imprinted polymers for α-tocopherol delivery. Drug Deliv. 2008; 15(4): 253-258.
- 13Wolfe M, Scopazzi C. Rheology of swellable microgel dispersions: influence of crosslink density. J Colloid Interface Sci. 1989; 133(1): 265-277.
- 14Mahkam M, Poorgholy N. Imprinted polymers as drug delivery vehicles for anti-inflammatory drugs. Nat Sci. 2011; 9: 163-168.
- 15Alvarez-Lorenzo C, Yanez F, Barreiro-Iglesias R, Concheiro A. Imprinted soft contact lenses as norfloxacin delivery systems. J Control Release. 2006; 113(3): 236-244.
- 16Norell MC, Andersson HS, Nicholls IA. Theophylline molecularly imprinted polymer dissociation kinetics: a novel sustained release drug dosage mechanism. J Mol Recognit: An Interdiscip J. 1998; 11(1–6): 98-102.
10.1002/(SICI)1099-1352(199812)11:1/6<98::AID-JMR399>3.0.CO;2-Y CAS PubMed Web of Science® Google Scholar
- 17Wang C, Javadi A, Ghaffari M, Gong S. A pH-sensitive molecularly imprinted nanospheres/hydrogel composite as a coating for implantable biosensors. Biomaterials. 2010; 31(18): 4944-4951.
- 18Puoci F, Iemma F, Cirillo G, Picci N, Matricardi P, Alhaique F. Molecularly imprinted polymers for 5-fluorouracil release in biological fluids. Molecules. 2007; 12(4): 805-814.
- 19Lok CM, Son R. Application of molecularly imprinted polymers in food sample analysis—a perspective. Int Food Res J. 2009; 16(2): 127-140.
- 20van Nostrum CF. Molecular imprinting: a new tool for drug innovation. Drug Discov Today Technol. 2005; 2(1): 119-124.
- 21Blumenthal GM, Cortazar P, Zhang JJ, et al. FDA approval summary: sunitinib for the treatment of progressive well-differentiated locally advanced or metastatic pancreatic neuroendocrine tumors. Oncologist. 2012; 17(8): 1108-1113. https://doi.org/10.1634/theoncologist.2012-0044
- 22Rock EP, Goodman V, Jiang JX, et al. Food and Drug Administration drug approval summary: Sunitinib malate for the treatment of gastrointestinal stromal tumor and advanced renal cell carcinoma. Oncologist. 2007; 12(1): 107-113.
- 23Parisi OI, Morelli C, Scrivano L, et al. Controlled release of sunitinib in targeted cancer therapy: smart magnetically responsive hydrogels as restricted access materials. RSC Adv. 2015; 5(80): 65308-65315.
- 24Scrivano L, Iacopetta D, Sinicropi MS, et al. Synthesis of sericin-based conjugates by click chemistry: enhancement of sunitinib bioavailability and cell membrane permeation. Drug Deliv. 2017; 24(1): 482-490.
- 25Rizza P, Pellegrino M, Caruso A, et al. 3-(Dipropylamino)-5-hydroxybenzofuro [2, 3-f] quinazolin-1 (2H)-one (DPA-HBFQ-1) plays an inhibitory role on breast cancer cell growth and progression. Eur J Med Chem. 2016; 107: 275-287.
- 26Meier F, Schott B, Riedel D, Mizaikoff B. Computational and experimental study on the influence of the porogen on the selectivity of 4-nitrophenol molecularly imprinted polymers. Anal Chim Acta. 2012; 744: 68-74.
- 27Haginaka J, Tabo H, Kagawa C. Uniformly sized molecularly imprinted polymers for d-chlorpheniramine: influence of a porogen on their morphology and enantioselectivity. J Pharm Biomed Anal. 2008; 46(5): 877-881.
- 28Muhammad P, Tu X, Liu J, Wang Y, Liu Z. Molecularly imprinted plasmonic substrates for specific and ultrasensitive immunoassay of trace glycoproteins in biological samples. ACS Appl Mater Interfaces. 2017; 9(13): 12082-12091.
- 29Militello V, Vetri V, Leone M. Conformational changes involved in thermal aggregation processes of bovine serum albumin. Biophys Chem. 2003; 105(1): 133-141.
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