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Layered Double Hydroxide Bionanocomposites
CHAPTER 16
Biomedical Applications of Polymer/ Layered Double Hydroxide Bionanocomposites M.R. Sanjay1, Suchart Siengchin1, Catalin Iulian Pruncu2,3, Mohammad Jawaid4, T. Senthil Muthu Kumar1,5 and N. Rajini5 1
Department of Mechanical and Process Engineering, The Sirindhorn International Thai-German Graduate School of Engineering (TGGS), King Mongkut’s University of Technology North Bangkok, Bangkok, Thailand 2Department of Mechanical Engineering, Imperial College London, London, United Kingdom 3Department of Mechanical Engineering, School of Engineering, University of Birmingham, Birmingham, United Kingdom 4Department of Biocomposite Technology, Institute of Tropical Forestry and Forest Products, University Putra Malaysia, Seri Kembangan, Malaysia 5 Department of Mechanical Engineering, Kalasalingam University, Krishnankoil, India
16.1 Introduction The combination of an inorganic material with polymers has been widely considered in recent years in order to develop a new bionanocomposite material [1]. Polymers derived from renewable resources are now considered as a promising substitute to traditional (petro) polymers because they can meet current environmental concerns in terms of environmental pollution, greenhouse gas emissions, and depletion of fossil resources [2,3]. The bionanocomposite structure represents a promising alternative for creating functional, bioinspired materials within wide-ranging medical applications [4]. Polymer-based layered compound nanocomposites have gained considerable attention due to their excellent properties [5]. In general, polymer/layered nanocomposite materials can be categorized into three different types, namely: (1) intercalated nanocomposites, (2) flocculated nanocomposites, and (3) exfoliated nanocomposites [6]. Recently, a different type of layered inorganic material, named layered double hydroxide (LDH), has established a great deal of interest for use as a nanofiller for composite structures [7,8]. LDH is well known for its potential applications in fields such as heterogeneous catalysis for biomedical applications, heat stabilizers, and halogen scavengers for polyvinyl chloride, etc. [9,10].
Nanostructured Polymer Composites for Biomedical Applications. DOI: https://doi.org/10.1016/B978-0-12-816771-7.00016-8 © 2019 Elsevier Inc. All rights reserved.
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316 Chapter 16 Polymer/LDH bionanocomposites have been extensively studied due to their good mechanical, barrier, and optical properties, along with their flammability resistance, which is very rarely present in any neat polymer [11 13]. Therefore many different polymers are currently being employed in this field. Some are stable and are used for perpetual applications such as poly(methylmetacrylate) (PMMA), polyethylene (PE), etc. In addition, biodegradable polymers such as polyglycolic and polylactic (PLA) acids are used in temporary applications [1,14]. The properties of biodegradable polymers might be enriched by the incorporation of nanoscale reinforcements [15]. It is noted that very few investigations have focused on polymer/LDH nanocomposites because there is a strong electrostatic interaction between highly charged hydroxide layers and intercalated anions to hinder the exfoliation of LDH layers. However, polymer/LDH nanocomposites could become a very promising new class of materials because of their exceptional thermal and mechanical properties [3,4,15 21]. This chapter reviews in detail the main properties and biomedical applications of polymer/LDH bionanocomposites used over the last decade.
16.2 Composition and Layered Double Hydroxide Structure LDH represent a class of chemical compounds that can be used to vary or incorporate characteristics into a variety of thermoplastic or thermoset polymer matrices [11]. LDH, also is known as anionic clay, may be represented by the [MII12xMIIIx(OH)2]An x/n. mH2O formula (see a representation in Fig. 16.1), where MII and MIII are divalent and trivalent metal cations within the brucite-like layer, such as Mg21 and Al31, respectively,
Figure 16.1 Pictographic structure of the LDH. LDH, Layered double hydroxide. Source: Reprinted (adapted) with permission from Leroux F, Besse JP. Polymer interleaved layered double hydroxide: a new emerging class of nanocomposites. Chem Mater 2001;13(10):3507 15 [22]. r2001 American Chemical Society.
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and An is an interlayer anion [23 25]. “Hydrotalcite” is a naturally occurring LDH form, which contains Mg21 and Al31 layers intercalated with a carbonate (CB) anion, denoted by the formula Mg6Al2(OH)16CO3 4H2O [8,26]. LDHs deliver advantages in terms of their structural homogeneity and configuration, high water content, nontoxicity and high reactivity towards organic anionic species that make them suitable for many applications. Their application in the biomedical field covers a complex mechanism of the release rate of various drugs and biomolecules and/or gene therapy; it addition it helps also to control the release rate of adsorption of different pesticides when used in the preparation of novel hybrid materials [11,27].
16.3 Properties of Polymer/Layered Double Hydroxide-Based Bionanocomposites Typically, incorporating polymers within the layers of LDH is carried out through numerous pathways such as direct intercalation, in situ polymerization, template synthesis, etc. [28,29]. The composition and ratio of the metals used in the layers and gallery anions of the LDH can be adjustable; this contributes to the LDHs having highly adjustable properties that can be suitable for use in an extensive range of applications [26]. LDHs generate a unique property called “memory effect,” for example, calcining hydrotalcite at around 450 C yields a mixture of oxides that can be rebuilt to the parental LDH by rehydration in an aqueous solution of the charge-balancing anion [26,30]. Wang et al. prepared a flame-retardant biodegradable poly(lactic acid) nanocomposite based on zinc aluminum LDH using melt-compounding directly. Their study demonstrated that the incorporation of flame retardant and ZnAl-LDH was very proficient in improving the flame retardance of a PLA composite [31]. Larocca et al. suggested that the polymer/LDH composite nanocoatings in combination with a high gas barrier, fast assembly, and high optical clarity can be suitable for the production of films used in food packaging and electronic encapsulation applications [16]. Nyambo et al. prepared polystyrene composites containing a LDH magnesium/aluminum (MgAl)-undecenoate (MAU-LDH) and ammonium polyphosphate (APP). This work exposes that the presence of MAU and APP individually has small effects on thermal stability and carbon formation, however the combination of both MAU and APP shows a remarkable stabilizing effect in the thermo-oxidative degradation stage while promoting char formation at high temperatures [32]. Tseng et al. investigated the thermal and mechanical properties of LDH/epoxy nanocomposites, while preparing LDH particles such as LDH-amino benzoate (LDHs-AB) and LDHs-CB particles by the coprecipitation method. LDH-AB/epoxy nanocomposites demonstrated outstanding performance in thermal and mechanical properties with excellent compatibility, but little enhancement and weak compatibility were recorded in LDH-CB/epoxy nanocomposites [24]. Kuila et al. prepared nanocomposites of ethylene vinyl acetate/low-density PE blended
318 Chapter 16 with varying amounts of organomodified layered double hydroxide (DS-LDH) by solution blending. The prepared LDH nanocomposites had enhanced mechanical and thermal properties with better solvent resistance property [33]. Chiang et al. described the preparation and physical properties of biodegradable nanocomposites fabricated using poly(L-lactide) (PLLA) and MgAl-LDH. The addition of PLA COOH-modified LDH (P-LDH) into a PLLA matrix induced a decrease in the degradation starting temperature and degradation activation energies with low mechanical properties [15]. Hsueh et al. enhanced the properties of nanocomposites by the incorporation of LDH nanolayers in a polyimide matrix [17]. Wang et al. also enhanced the tensile modulus of the nanocomposites by incorporating the 10-undecenoate intercalated LDH (LDH-U) into the PMMA matrix [19]. Lv et al. studied the properties of nanocomposites based on diglycidyl ether of bisphenol A, hyperbranched polymer (E1), and organically modified LDH (O-LDH). The O-LDH nanolayers were well dispersed in the polymer matrix and showed good compatibility, playing the role of crosslinkers during the curing process [23]. Chhetri et al. enhanced the mechanical, rheological, and thermal properties of epoxy composites by LDH nanolayers [34].
16.4 Biomedical Applications of Polymer/Layered Double Hydroxide The main use of polymer/LDH composites in biomedical applications includes their use as a heat stabilizer, molecular sieve, or ion exchanger, for designing sensors and biosensors based on clay-modified electrodes, as halogen scavengers, etc. [10]. Bio-based polymers with LDHs are identified in a wide range of applications, especially for tissue engineering, drug delivery, and gene therapy due to their great compatibility, noncytotoxicity and noninflammatory nature toward the biological system [35,36]. Ribeiro et al. developed a hybrid system by intercalation of enalaprilate between the main layers of the LDH, and coating them with xyloglucan that protects the drug by an ion exchange reaction. Their investigation helped to reduce the amount of ingested drugs, reducing the stress factor and improving quality of life [37]. Recently, Cao et al. worked on LDH nanoplates for pH-responsive cancer therapy. They used a coating with an ultrathin mesoporous silica layer (LDH@MS) that is presented schematically in Fig. 16.2 [38]. Peng et al. synthesized monolayer LDH nanosheets with high doxorubicin loading content for fast drug release [39]. Furthermore, Shi et al. produced silica nanoparticles doped with manganese and established tumor microenvironment-sensitive biodegradation and theranostic functions [40]. Wu et al. examined LDH nanoparticles and small interfering RNA for efficient knockdown of the target gene [41]. Alcantara et al. introduced hybrid materials based on the combination of LDH and two biopolymers (a protein and a polysaccharide) to produce LDH biopolymer nanocomposites which are able to act as effective drug-delivery systems [42]. Han et al. prepared a hybrid material based on chitosan and LDHs to support the
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Figure 16.2 Representation of a pH-responsive drug-delivery system based on mesoporous silica-coated LDH (LDH@MS) for cancer therapy. LDH, Layered double hydroxide. Source: Reprinted (adapted) with permission from Cao W, Muhammad F, Cheng Y, Zhou M, Wang Q, Lou Z, et al. Acid susceptible ultrathin mesoporous silica coated on layered double hydroxide nanoplates for pH responsive cancer therapy. ACS Appl Bio Mater 2018;1(3):928 35. r2018 American Chemical Society.
immobilization of enzymes and application of amperometric phenol biosensor [43]. Dagnon et al. examined a possible decrease in cell proliferation while simultaneously increasing the mechanical performance by adding Zn Al layered LDH organically modified with ibuprofen dispersed in PLLA [44]. The effectiveness of using biocomposites based on LDH for the synthesis of phosphorylated sugars or the detection of important pharmaceutical molecules makes them very promising materials for use as biosensors, in biosynthesis, biodegradation, or energy conversion [45,46].
16.5 Concluding Remarks LDHs are a group of anionic clay materials that have attracted increasing attention in recent years for biomedical applications, such as gene delivery, vaccine delivery, and drug delivery. This chapter presents a review of the polymer/LDH bionanocomposites that are used in various biomedical applications. It is noted that, in the field of advanced ecological materials, bionanocomposite materials represent a fast-growing field of research and development due to their current potential in diverse applications. Significant research progress can be further extended in the use of the polymer/LDH bionanocomposites for various medical applications.
320 Chapter 16
Acknowledgment This research was partly supported by the King Mongkut’s University of Technology North Bangkok through the PostDoc Program (Grant No. KMUTNB-61-Post-001 and KMUTNB-62-KNOW-13).
References [1] San Roma´n MS, Holgado MJ, Salinas B, Rives V. Drug release from layered double hydroxides and from their polylactic acid (PLA) nanocomposites. Appl Clay Sci 2013;71:1 7. [2] Jenck JF, Agterberg F, Droescher MJ. Products and processes for a sustainable chemical industry: a review of achievements and prospects. Green Chem 2004;6(11):544 56. [3] Raquez JM, Habibi Y, Murariu M, Dubois P. Polylactide (PLA)-based nanocomposites. Prog Poly Sci 2013;38(10 11):1504 42. [4] Reddy MM, Vivekanandhan S, Misra M, Bhatia SK, Mohanty AK. Biobased plastics and bionanocomposites: current status and future opportunities. Prog Poly Sci 2013;38(10 11):1653 89. [5] Wypych F, Satyanarayana KG. Functionalization of single layers and nanofibers: a new strategy to produce polymer nanocomposites with optimized properties. J Colloid Interface Sci 2015;285(2):532 43. [6] Ray SS, Okamoto M. Polymer/layered silicate nanocomposites: a review from preparation to processing. Prog Poly Sci 2003;28(11):1539 641. [7] Lingaiah S, Sadler R, Ibeh C, Shivakumar K. A method of visualization of inorganic nanoparticles dispersion in nanocomposites. Compos Part B Eng 2008;39(1):196 201. [8] Nyambo C, Chen D, Su S, Wilkie CA. Does organic modification of layered double hydroxides improve the fire performance of PMMA? Polym Degrad Stab 2009;94(8):1298 306. [9] Lin YJ, Li DQ, Evans DG, Duan X. Modulating effect of Mg Al CO3 layered double hydroxides on the thermal stability of PVC resin. Polym Degrad Stab 2005;88(2):286 93. [10] Costa FR, Satapathy BK, Wagenknecht U, Weidisch R, Heinrich G. Morphology and fracture behaviour of polyethylene/Mg Al layered double hydroxide (LDH) nanocomposites. Eur Poly J 2006;42 (9):2140 52. [11] Becker CM, Gabbardo AD, Wypych F, Amico SC. Mechanical and flame-retardant properties of epoxy/ Mg Al LDH composites. Compos Part A Appl Sci Manuf 2011;42(2):196 202. [12] Chan YN, Juang TY, Liao YL, Dai SA, Lin JJ. Preparation of clay/epoxy nanocomposites by layereddouble-hydroxide initiated self-polymerization. Polymer 2008;49(22):4796 801. [13] Wang L, Wang K, Chen L, Zhang Y, He C. Preparation, morphology and thermal/mechanical properties of epoxy/nanoclay composite. Compos Part A Appl Sci Manuf 2006;37(11):1890 6. [14] Darder M, Lo´pez-Blanco M, Aranda P, Leroux F, Ruiz-Hitzky E. Bio-nanocomposites based on layered double hydroxides. Chem Mater 2005;17(8):1969 77. [15] Chiang MF, Wu TM. Synthesis and characterization of biodegradable poly(L-lactide)/layered double hydroxide nanocomposites. Compos Sci Technol 2010;70(1):110 15. [16] Larocca NM, Bernardes Filho R, Pessan LA. Influence of layer-by-layer deposition techniques and incorporation of layered double hydroxides (LDH) on the morphology and gas barrier properties of polyelectrolytes multilayer thin films. Surf Coat Technol 2018;349:1 12. [17] Hsueh HB, Chen CY. Preparation and properties of LDHs/polyimide nanocomposites. Polymer 2003;44 (4):1151 61. [18] Du L, Qu B. Structural characterization and thermal oxidation properties of LLDPE/MgAl-LDH nanocomposites. J Mater Chem 2006;16(16):1549 54. [19] Wang GA, Wang CC, Chen CY. The disorderly exfoliated LDHs/PMMA nanocomposites synthesized by in situ bulk polymerization: the effects of LDH-U on thermal and mechanical properties. Polym Degrad Stab 2006;91(10):2443 50.
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[20] Ding P, Zhang M, Gai J, Qu B. Homogeneous dispersion and enhanced thermal properties of polystyrenelayered double hydroxide nanocomposites prepared by in situ reversible addition fragmentation chain transfer (RAFT) polymerization. J Mater Chem 2007;17(11):1117 22. [21] Costa FR, Saphiannikova M, Wagenknecht U, Heinrich G. Layered double hydroxide based polymer nanocomposites. Wax crystal control nanocomposites stimuli-responsive polymers. Berlin, Heidelberg: Springer; 2007. p. 101 68. [22] Leroux F, Besse JP. Polymer interleaved layered double hydroxide: a new emerging class of nanocomposites. Chem Mater 2001;13(10):3507 15. [23] Lv S, Yuan Y, Shi W. Strengthening and toughening effects of layered double hydroxide and hyperbranched polymer on epoxy resin. Prog Org Coat 2009;65(4):425 30. [24] Tseng CH, Hsueh HB, Chen CY. Effect of reactive layered double hydroxides on the thermal and mechanical properties of LDHs/epoxy nanocomposites. Compos Sci Technol 2007;67(11 12):2350 62. [25] Satyanarayana KG. Clay surfaces: fundamentals and applications, Vol. 1. Elsevier; 2004. [26] Manzi-Nshuti C, Wang D, Hossenlopp JM, Wilkie CA. The role of the trivalent metal in an LDH: synthesis, characterization and fire properties of thermally stable PMMA/LDH systems. Polym Degrad Stab 2009;94(4):705 11. [27] Li B, Hu Y, Zhang R, Chen Z, Fan W. Preparation of the poly(vinyl alcohol)/layered double hydroxide nanocomposite. Mater Res Bull 2003;38(11 12):1567 72. [28] Peng H, Tjiu WC, Shen L, Huang S, He C, Liu T. Preparation and mechanical properties of exfoliated CoAl layered double hydroxide (LDH)/polyamide 6 nanocomposites by in situ polymerization. Compos Sci Technol 2009;69(7 8):991 6. [29] Li B, Hu Y, Liu J, Chen Z, Fan W. Preparation of poly(methyl methacrylate)/LDH nanocomposite by exfoliation-adsorption process. Colloid Polym Sci 2003;281(10):998 1001. [30] Kooli F, Depege C, Ennaqadi A, De Roy A, Besse JP. Rehydration of Zn-Al layered double hydroxides. Clays Clay Min 1997;45(1):92 8. [31] Wang DY, Leuteritz A, Wang YZ, Wagenknecht U, Heinrich G. Preparation and burning behaviors of flame retarding biodegradable poly(lactic acid) nanocomposite based on zinc aluminum layered double hydroxide. Polym Degrad Stab 2010;95(12):2474 80. [32] Nyambo C, Kandare E, Wang D, Wilkie CA. Flame-retarded polystyrene: investigating chemical interactions between ammonium polyphosphate and MgAl layered double hydroxide. Polym Degrad Stab 2008;93(9):1656 63. [33] Kuila T, Srivastava SK, Bhowmick AK, Saxena AK. Thermoplastic polyolefin based polymer blendlayered double hydroxide nanocomposites. Compos Sci Technol 2008;68(15 16):3234 9. [34] Chhetri S, Adak NC, Samanta P, Murmu NC, Kuila T. Rheological, mechanical, and thermal properties of silane grafted layered double hydroxide/epoxy composites. Ind Eng Chem Res 2018;57:8729 39. [35] Ratner BD, Hoffman AS, Schoen FJ, Lemons JE. Biomaterials science: an introduction to materials in medicine. Elsevier; 2004. [36] Ruiz-Hitzky E, Aranda P, Darder M, Rytwo G. Hybrid materials based on clays for environmental and biomedical applications. J Mater Chem 2010;20(42):9306 21. [37] Ribeiro C, Arizaga GG, Wypych F, Sierakowski MR. Nanocomposites coated with xyloglucan for drug delivery: in vitro studies. Int J Pharm 2009;367(1 2):204 10. [38] Cao W, Muhammad F, Cheng Y, Zhou M, Wang Q, Lou Z, et al. Acid susceptible ultrathin mesoporous silica coated on layered double hydroxide nanoplates for pH responsive cancer therapy. ACS Appl Bio Mater 2018;1(3):928 35. [39] Peng L, Mei X, He J, Xu J, Zhang W, Liang R, et al. Monolayer nanosheets with an extremely high drug loading toward controlled delivery and cancer theranostics. Adv Mater 2018;30(16):1707389. [40] Shi J, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer 2017;17(1):20. [41] Wu Y, Gu W, Chen C, Do ST, Xu ZP. Optimization of formulations consisting of layered double hydroxide nanoparticles and small interfering RNA for efficient knockdown of the target gene. ACS Omega 2018;3(5):4871 7.
322 Chapter 16 [42] Alcantara AC, Aranda P, Darder M, Ruiz-Hitzky E. Bionanocomposites based on alginate-zein/layered double hydroxide materials as drug delivery systems. J Mater Chem 2010;20(42):9495 504. [43] Han E, Shan D, Xue H, Cosnier S. Hybrid material based on chitosan and layered double hydroxides: characterization and application to the design of amperometric phenol biosensor. Biomacromolecules 2007;8(3):971 5. [44] Dagnon KL, Ambadapadi S, Shaito A, Ogbomo SM, DeLeon V, Golden TD, et al. Poly(L-lactic acid) nanocomposites with layered double hydroxides functionalized with ibuprofen. J Appl Polym Sci 2009;113(3):1905 15. [45] Darder M, Aranda P, Ruiz-Hitzky E. Bionanocomposites: a new concept of ecological, bioinspired, and functional hybrid materials. Adv Mater 2007;19(10):1309 19. [46] Taviot-Gue´ho C, Pre´vot V, Forano C, Renaudin G, Mousty C, Leroux F. Tailoring hybrid layered double hydroxides for the development of innovative applications. Adv Funct Mater 2018;28(27):1703868.
Biomedical Applications of Polymer/ Layered Double Hydroxide Bionanocomposites M.R. Sanjay1, Suchart Siengchin1, Catalin Iulian Pruncu2,3, Mohammad Jawaid4, T. Senthil Muthu Kumar1,5 and N. Rajini5 1
Department of Mechanical and Process Engineering, The Sirindhorn International Thai-German Graduate School of Engineering (TGGS), King Mongkut’s University of Technology North Bangkok, Bangkok, Thailand 2Department of Mechanical Engineering, Imperial College London, London, United Kingdom 3Department of Mechanical Engineering, School of Engineering, University of Birmingham, Birmingham, United Kingdom 4Department of Biocomposite Technology, Institute of Tropical Forestry and Forest Products, University Putra Malaysia, Seri Kembangan, Malaysia 5 Department of Mechanical Engineering, Kalasalingam University, Krishnankoil, India
16.1 Introduction The combination of an inorganic material with polymers has been widely considered in recent years in order to develop a new bionanocomposite material [1]. Polymers derived from renewable resources are now considered as a promising substitute to traditional (petro) polymers because they can meet current environmental concerns in terms of environmental pollution, greenhouse gas emissions, and depletion of fossil resources [2,3]. The bionanocomposite structure represents a promising alternative for creating functional, bioinspired materials within wide-ranging medical applications [4]. Polymer-based layered compound nanocomposites have gained considerable attention due to their excellent properties [5]. In general, polymer/layered nanocomposite materials can be categorized into three different types, namely: (1) intercalated nanocomposites, (2) flocculated nanocomposites, and (3) exfoliated nanocomposites [6]. Recently, a different type of layered inorganic material, named layered double hydroxide (LDH), has established a great deal of interest for use as a nanofiller for composite structures [7,8]. LDH is well known for its potential applications in fields such as heterogeneous catalysis for biomedical applications, heat stabilizers, and halogen scavengers for polyvinyl chloride, etc. [9,10].
Nanostructured Polymer Composites for Biomedical Applications. DOI: https://doi.org/10.1016/B978-0-12-816771-7.00016-8 © 2019 Elsevier Inc. All rights reserved.
315
316 Chapter 16 Polymer/LDH bionanocomposites have been extensively studied due to their good mechanical, barrier, and optical properties, along with their flammability resistance, which is very rarely present in any neat polymer [11 13]. Therefore many different polymers are currently being employed in this field. Some are stable and are used for perpetual applications such as poly(methylmetacrylate) (PMMA), polyethylene (PE), etc. In addition, biodegradable polymers such as polyglycolic and polylactic (PLA) acids are used in temporary applications [1,14]. The properties of biodegradable polymers might be enriched by the incorporation of nanoscale reinforcements [15]. It is noted that very few investigations have focused on polymer/LDH nanocomposites because there is a strong electrostatic interaction between highly charged hydroxide layers and intercalated anions to hinder the exfoliation of LDH layers. However, polymer/LDH nanocomposites could become a very promising new class of materials because of their exceptional thermal and mechanical properties [3,4,15 21]. This chapter reviews in detail the main properties and biomedical applications of polymer/LDH bionanocomposites used over the last decade.
16.2 Composition and Layered Double Hydroxide Structure LDH represent a class of chemical compounds that can be used to vary or incorporate characteristics into a variety of thermoplastic or thermoset polymer matrices [11]. LDH, also is known as anionic clay, may be represented by the [MII12xMIIIx(OH)2]An x/n. mH2O formula (see a representation in Fig. 16.1), where MII and MIII are divalent and trivalent metal cations within the brucite-like layer, such as Mg21 and Al31, respectively,
Figure 16.1 Pictographic structure of the LDH. LDH, Layered double hydroxide. Source: Reprinted (adapted) with permission from Leroux F, Besse JP. Polymer interleaved layered double hydroxide: a new emerging class of nanocomposites. Chem Mater 2001;13(10):3507 15 [22]. r2001 American Chemical Society.
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and An is an interlayer anion [23 25]. “Hydrotalcite” is a naturally occurring LDH form, which contains Mg21 and Al31 layers intercalated with a carbonate (CB) anion, denoted by the formula Mg6Al2(OH)16CO3 4H2O [8,26]. LDHs deliver advantages in terms of their structural homogeneity and configuration, high water content, nontoxicity and high reactivity towards organic anionic species that make them suitable for many applications. Their application in the biomedical field covers a complex mechanism of the release rate of various drugs and biomolecules and/or gene therapy; it addition it helps also to control the release rate of adsorption of different pesticides when used in the preparation of novel hybrid materials [11,27].
16.3 Properties of Polymer/Layered Double Hydroxide-Based Bionanocomposites Typically, incorporating polymers within the layers of LDH is carried out through numerous pathways such as direct intercalation, in situ polymerization, template synthesis, etc. [28,29]. The composition and ratio of the metals used in the layers and gallery anions of the LDH can be adjustable; this contributes to the LDHs having highly adjustable properties that can be suitable for use in an extensive range of applications [26]. LDHs generate a unique property called “memory effect,” for example, calcining hydrotalcite at around 450 C yields a mixture of oxides that can be rebuilt to the parental LDH by rehydration in an aqueous solution of the charge-balancing anion [26,30]. Wang et al. prepared a flame-retardant biodegradable poly(lactic acid) nanocomposite based on zinc aluminum LDH using melt-compounding directly. Their study demonstrated that the incorporation of flame retardant and ZnAl-LDH was very proficient in improving the flame retardance of a PLA composite [31]. Larocca et al. suggested that the polymer/LDH composite nanocoatings in combination with a high gas barrier, fast assembly, and high optical clarity can be suitable for the production of films used in food packaging and electronic encapsulation applications [16]. Nyambo et al. prepared polystyrene composites containing a LDH magnesium/aluminum (MgAl)-undecenoate (MAU-LDH) and ammonium polyphosphate (APP). This work exposes that the presence of MAU and APP individually has small effects on thermal stability and carbon formation, however the combination of both MAU and APP shows a remarkable stabilizing effect in the thermo-oxidative degradation stage while promoting char formation at high temperatures [32]. Tseng et al. investigated the thermal and mechanical properties of LDH/epoxy nanocomposites, while preparing LDH particles such as LDH-amino benzoate (LDHs-AB) and LDHs-CB particles by the coprecipitation method. LDH-AB/epoxy nanocomposites demonstrated outstanding performance in thermal and mechanical properties with excellent compatibility, but little enhancement and weak compatibility were recorded in LDH-CB/epoxy nanocomposites [24]. Kuila et al. prepared nanocomposites of ethylene vinyl acetate/low-density PE blended
318 Chapter 16 with varying amounts of organomodified layered double hydroxide (DS-LDH) by solution blending. The prepared LDH nanocomposites had enhanced mechanical and thermal properties with better solvent resistance property [33]. Chiang et al. described the preparation and physical properties of biodegradable nanocomposites fabricated using poly(L-lactide) (PLLA) and MgAl-LDH. The addition of PLA COOH-modified LDH (P-LDH) into a PLLA matrix induced a decrease in the degradation starting temperature and degradation activation energies with low mechanical properties [15]. Hsueh et al. enhanced the properties of nanocomposites by the incorporation of LDH nanolayers in a polyimide matrix [17]. Wang et al. also enhanced the tensile modulus of the nanocomposites by incorporating the 10-undecenoate intercalated LDH (LDH-U) into the PMMA matrix [19]. Lv et al. studied the properties of nanocomposites based on diglycidyl ether of bisphenol A, hyperbranched polymer (E1), and organically modified LDH (O-LDH). The O-LDH nanolayers were well dispersed in the polymer matrix and showed good compatibility, playing the role of crosslinkers during the curing process [23]. Chhetri et al. enhanced the mechanical, rheological, and thermal properties of epoxy composites by LDH nanolayers [34].
16.4 Biomedical Applications of Polymer/Layered Double Hydroxide The main use of polymer/LDH composites in biomedical applications includes their use as a heat stabilizer, molecular sieve, or ion exchanger, for designing sensors and biosensors based on clay-modified electrodes, as halogen scavengers, etc. [10]. Bio-based polymers with LDHs are identified in a wide range of applications, especially for tissue engineering, drug delivery, and gene therapy due to their great compatibility, noncytotoxicity and noninflammatory nature toward the biological system [35,36]. Ribeiro et al. developed a hybrid system by intercalation of enalaprilate between the main layers of the LDH, and coating them with xyloglucan that protects the drug by an ion exchange reaction. Their investigation helped to reduce the amount of ingested drugs, reducing the stress factor and improving quality of life [37]. Recently, Cao et al. worked on LDH nanoplates for pH-responsive cancer therapy. They used a coating with an ultrathin mesoporous silica layer (LDH@MS) that is presented schematically in Fig. 16.2 [38]. Peng et al. synthesized monolayer LDH nanosheets with high doxorubicin loading content for fast drug release [39]. Furthermore, Shi et al. produced silica nanoparticles doped with manganese and established tumor microenvironment-sensitive biodegradation and theranostic functions [40]. Wu et al. examined LDH nanoparticles and small interfering RNA for efficient knockdown of the target gene [41]. Alcantara et al. introduced hybrid materials based on the combination of LDH and two biopolymers (a protein and a polysaccharide) to produce LDH biopolymer nanocomposites which are able to act as effective drug-delivery systems [42]. Han et al. prepared a hybrid material based on chitosan and LDHs to support the
Biomedical Applications of Polymer/Layered Double Hydroxide Bionanocomposites
319
Figure 16.2 Representation of a pH-responsive drug-delivery system based on mesoporous silica-coated LDH (LDH@MS) for cancer therapy. LDH, Layered double hydroxide. Source: Reprinted (adapted) with permission from Cao W, Muhammad F, Cheng Y, Zhou M, Wang Q, Lou Z, et al. Acid susceptible ultrathin mesoporous silica coated on layered double hydroxide nanoplates for pH responsive cancer therapy. ACS Appl Bio Mater 2018;1(3):928 35. r2018 American Chemical Society.
immobilization of enzymes and application of amperometric phenol biosensor [43]. Dagnon et al. examined a possible decrease in cell proliferation while simultaneously increasing the mechanical performance by adding Zn Al layered LDH organically modified with ibuprofen dispersed in PLLA [44]. The effectiveness of using biocomposites based on LDH for the synthesis of phosphorylated sugars or the detection of important pharmaceutical molecules makes them very promising materials for use as biosensors, in biosynthesis, biodegradation, or energy conversion [45,46].
16.5 Concluding Remarks LDHs are a group of anionic clay materials that have attracted increasing attention in recent years for biomedical applications, such as gene delivery, vaccine delivery, and drug delivery. This chapter presents a review of the polymer/LDH bionanocomposites that are used in various biomedical applications. It is noted that, in the field of advanced ecological materials, bionanocomposite materials represent a fast-growing field of research and development due to their current potential in diverse applications. Significant research progress can be further extended in the use of the polymer/LDH bionanocomposites for various medical applications.
320 Chapter 16
Acknowledgment This research was partly supported by the King Mongkut’s University of Technology North Bangkok through the PostDoc Program (Grant No. KMUTNB-61-Post-001 and KMUTNB-62-KNOW-13).
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