Abstract
In recent years, organic-inorganic hybrid nanocarriers are explored for effective drug delivery and preferable disease treatments. In this study, using 5-fluorouracil(5-FU)as electronegative model drug, a new type of organic-inorganic hybrid drug delivery system(LDH/HA-PEG/5-FU)was conceived and manufactured by the adsorption of PEGylated hyaluronic acid(HA-PEG)on the surface of layered double hydroxide(LDH, prepared via hydrothermal method)and the intercalation of 5-FU in the interlamination of LDH via ion exchange strategy. The drug loading amount of LDH/HA-PEG/5-FU achieved as high as 34.2%. LDH, LDH/5-FU and LDH/HA-PEG/5- FU were characterized by FT-IR, XRD, TGA, laser particle size analyzer and SEM. With the benefit of pHdegradable feature of LDH and enzyme-degradable feature of HA, LDH/HA-PEG/5-FU showed pH-degradable and enzyme-degradable capacity in in vitro drug release. Moreover, the drug carrier LDH/HA-PEG contained biocompatible PEG and tumor-targeted HA, resulting in lower cytotoxicity and better endocytosis compared with LDH in vitro. It was suggested that the organic-inorganic hybrid drug delivery system, which was endowed with the properties of controlled release, low toxicity and tumor-targeting delivery for ameliorative cancer therapy, was advisable and might be applied further to fulfill other treatments.
Similar content being viewed by others
References
Allen T M, Cullis P R. Drug delivery systems: Entering the mainstream[J]. Science, 2004, 303(5665): 1818–1822.
Han S, Wan H, Lin D et al. Contribution of hydrophobic/hydrophilic modification on cationic chains of poly(epsilon-caprolactone)-graft-poly(dimethylamino ethylmethacrylate) amphiphilic co-polymer in gene delivery[J]. Acta Biomaterialia, 2014, 10(2): 670–679.
Chiang Y T, Lo C L. pH-responsive polymer-liposomes for intracellular drug delivery and tumor extracellular matrix switched-on targeted cancer therapy[J]. Biomaterials, 2014, 35(20): 5414–5424.
Gifford I, Vreeland W, Grdanovska S et al. Liposome based delivery of a boron-containing cholesteryl ester for high-LET particle-induced damage of prostate cancer cells: A boron neutron capture therapy study[J]. International Journal of Radiation Biology, 2014, 90(6): 480–485.
Khatri N, Baradia D, Vhora I et al. cRGD grafted liposomes containing inorganic nano-precipitate complexed siRNA for intracellular delivery in cancer cells[J]. Journal of Controlled Release, 2014, 182: 45–57.
Jeong B, Bae Y H, Lee D S et al. Biodegradable block copolymers as injectable drug-delivery systems[J]. Nature, 1997, 388(6645): 860–862.
Mathiowitz E, Jacob J S, Jong Y S et al. Biologically erodable microspheres as potential oral drug delivery systems[J]. Nature, 1997, 386(6623): 410–414.
Mundargi R C, Babu V R, Rangaswamy V et al. Nano/micro technologies for delivering macromolecular therapeutics using poly(D,L-lactide-co-glycolide) and its derivatives[J] Journal of Controlled Release, 2008, 125(3): 193–209.
Kreilgaard M. Influence of microemulsions on cutaneous drug delivery[J]. Advanced Drug Delivery Reviews, 2002, 54: S77–S98.
Chen M L, He Y J, Chen X W et al. Quantum dots conjugated with Fe3O4-filled carbon nanotubes for cancertargeted imaging and magnetically guided drug delivery[J]. Langmuir, 2012, 28(47): 16469–16476.
Jiang Z L, Dong B, Chen B T et al. Multifunctional Au@mSiO2/rhodamine B isothiocyanate nanocomposites: Cell imaging, photocontrolled drug release, and photothermal therapy for cancer cells[J]. Small, 2013, 9(4): 604–612.
Samanta B, Yan H, Fischer N O et al. Protein-passivated Fe3O4 nanoparticles: Low toxicity and rapid heating for thermal therapy[J]. Journal of Materials Chemistry, 2008, 18(11): 1204–1208.
Xuan S H, Wang F, Lai J M Y et al. Synthesis of biocompatible, mesoporous Fe3O4 nano/microspheres with large surface area for magnetic resonance imaging and therapeutic applications[J]. ACS Applied Materials & Interfaces, 2011, 3(2): 237–244.
Yu T, Malugin A, Ghandehari H. Impact of silica nanoparticle design on cellular toxicity and hemolytic activity[J]. ACS Nano, 2011, 5(7): 5717–5728.
Kim J, Lee J E, Lee S H et al. Designed fabrication of a multifunctional polymer nanomedical platform for simultaneous cancer-targeted imaging and magnetically guided drug delivery[J]. Advanced Materials, 2008, 20(3): 478–491.
Yang X, Zhang X, Ma Y et al. Superparamagnetic graphene oxide-Fe3O4 nanoparticles hybrid for controlled targeted drug carriers[J]. Journal of Materials Chemistry, 2009, 19(18): 2710–2714.
Chen Y, Chen H, Zeng D et al. Core/shell structured hollow mesoporous nanocapsules: A potential platform for simultaneous cell imaging and anticancer drug delivery[J]. ACS Nano, 2010, 4(10): 6001–6013.
Choudary B M, Madhi S, Chowdari N S et al. Layered double hydroxide supported nanopalladium catalyst for Heck-, Suzuki-, Sonogashira-, and Stille-type coupling reactions of chloroarenes[J]. Journal of the American Chemical Society, 2002, 124(47): 14127–14136.
Costa F R, Wagenknecht U, Heinrich G. LDPE/Mg-Al layered double hydroxide nanocomposite: Thermal and flammability properties[J]. Polymer Degradation and Stability, 2007, 92(10): 1813–1823.
Wang Z Y, Han E H, Ke W. Influence of nano-LDHs on char formation and fire-resistant properties of flameretardant coating[J]. Progress in Organic Coatings, 2005, 53(1): 29–37.
Liu J, Li Y, Huang X et al. Layered double hydroxide nano-and microstructures grown directly on metal substrates and their calcined products for application as Liion battery electrodes[J]. Advanced Functional Materials, 2008, 18(9): 1448–1458.
Gao Z, Wang J, Li Z et al. Graphene nanosheet/Ni2+/Al3+ layered double-hydroxide composite as a novel electrode for a supercapacitor[J]. Chemistry of Materials, 2011, 23(15): 3509–3516.
Wang L, Wang D, Dong X Y et al. Layered assembly of graphene oxide and Co-Al layered double hydroxide nanosheets as electrode materials for supercapacitors[J]. Chemical Communications, 2011, 47(12): 3556–3558.
Evans D G, Xue D A. Preparation of layered double hydroxides and their applications as additives in polymers, as precursors to magnetic materials and in biology and medicine[J]. Chemical Communications, 2006, 37(5): 485–496.
Sideris P J, Nielsen U G, Gan Z et al. Mg/Al ordering in layered double hydroxides revealed by multinuclear NMR spectroscopy[J]. Science, 2008, 321(5885): 113–117.
You Y W, Vance G F, Zhao H T. Selenium adsorption on Mg-Al and Zn-Al layered double hydroxides[J]. Applied Clay Science, 2001, 20(1/2): 13–25.
Khan A I, Lei L X, Norquist A J et al. Intercalation and controlled release of pharmaceutically active compounds from a layered double hydroxide[J]. Chemical Communications, 2001, 37(22): 2342–2343.
Choy J H, Jung J S, Oh J M et al. Layered double hydroxide as an efficient drug reservoir for folate derivatives[J]. Biomaterials, 2004, 25(15): 3059–3064.
Rojas R, Jimenez-Kairuz A F, Manzo R H et al. Release kinetics from LDH-drug hybrids: Effect of layers stacking and drug solubility and polarity[J]. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2014, 463: 37–43.
Li B X, He J, Evans D G et al. Inorganic layered double hydroxides as a drug delivery system—Intercalation and in vitro release of fenbufen[J] Applied Clay Science, 2004, 27(3/4): 199–207.
Ladewig K, Niebert M, Xu Z P et al. Efficient siRNA delivery to mammalian cells using layered double hydroxide nanoparticles[J]. Biomaterials, 2010, 31(7): 1821–1829.
Wong Y, Markham K, Xu Z P et al. Efficient delivery of siRNA to cortical neurons using layered double hydroxide nanoparticles[J]. Biomaterials, 2010, 31(33): 8770–8779.
Desigaux L, Ben Belkacem M, Richard P et al. Selfassembly and characterization of layered double hydroxide/DNA hybrids[J]. Nano Letters, 2006, 6(2): 199–204.
Li L, Gu W Y, Chen J Z et al. Co-delivery of siRNAs and anti-cancer drugs using layered double hydroxide nanoparticles[J]. Biomaterials, 2014, 35(10): 3331–3339.
Xu Z P, Stevenson G S, Lu C Q et al. Stable suspension of layered double hydroxide nanoparticles in aqueous solution[J]. Journal of the American Chemical Society, 2006, 128(1): 36–37.
Zhang W, Cheng Q, Guo S et al. Gene transfection efficacy and biocompatibility of polycation/DNA complexes coated with enzyme degradable PEGylated hyaluronic acid[J]. Biomaterials, 2013, 34(27): 6495–6503.
Wu X, Li H, Song S et al. Facile synthesis of camptothecin intercalated layered double hydroxide nanohybrids via a coassembly route[J]. International Journal of Pharmaceutics, 2013, 454(1): 453–461.
Pan C, Shen L, Shang S et al. Preparation of superhydrophobic and UV blocking cotton fabric via solgel method and self-assembly[J]. Applied Surface Science, 2012, 259: 110–117.
Lin X N, Deng L D, Xu Y S et al. Thermosensitive in situ hydrogel of paclitaxel conjugated poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) [J]. Soft Matter, 2012, 8(12): 3470–3477.
Azhar F F, Olad A. A study on sustained release formulations for oral delivery of 5-fluorouracil based on alginate-chitosan/montmorillonite nanocomposite systems [J]. Applied Clay Science, 2014, 101: 288–296.
Monash P, Pugazhenthi G. Utilization of calcined Ni-Al layered double hydroxide (LDH) as an adsorbent for removal of methyl orange dye from aqueous solution[J]. Environmental Progress & Sustainable Energy, 2014, 33(1): 154–159.
Tannock I F, Rotin D. Acid pH in tumors and its potential for therapeutic exploitation[J]. Cancer Research, 1989, 49(16): 4373–4384.
Picart C, Schneider A, Etienne O et al. Controlled degradability of polysaccharide multilayer films in vitro and in vivo[J]. Advanced Functional Materials, 2005, 15(11): 1771–1780.
Ghosh P, Guidolin D. Potential mechanism of action of intra-articular hyaluronan therapy in osteoarthritis: Are the effects molecular weight dependent?[J]. Seminars in Arthritis and Rheumatism, 2002, 32(1): 10–37.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by the National Natural Science Foundation of China(No. 81371667, No. 31271073).
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Dong, A., Li, X., Wang, W. et al. Layered double hydroxide modified by PEGylated hyaluronic acid as a hybrid nanocarrier for targeted drug delivery. Trans. Tianjin Univ. 22, 237–246 (2016). https://doi.org/10.1007/s12209-016-2710-2
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12209-016-2710-2