English

• 1. INTRODUCTION

  Polysaccharides are natural biomaterials and widely used carriers for targeted drug delivery systems^{[1, 2]} due to the following advantages: they exist in a wide variety and are relatively inexpensive, they exhibit high biocompatibility and biodegradability, and they are nontoxic and nonreactive^[3]. Several natural gel matrices for drug-controlled release are gelatin^[4-6], graphene^{[7, 8]}, starch^{[9, 10]}, and cellulose^[11]. Polysaccharide gels have a continuous and stable three-dimensional network structure, and the development of controlled drug delivery systems for nontoxic, biodegradable and biocompatible natural polymers has broad application prospects^[3]. The potential applications of pH-sensitive hydrogels in controlled-release systems have been extensively studied.

  KGM is a natural, nontoxic and easily deacetylated aerogelforming polymer polysaccharide with biocompatibility, high abundance, and low cost, and it is water-soluble^{[12, 13]}. Its main chain is polymerized by D-mannose and D-glucose with an α-1, 4-pyranoside bond and a small number of acetyl groups at the C-6 position of the side chain^[10-12]. It can be hydrolyzed only by α-mannanase at the end of the small intestine; thus, KGM has broad application prospects in controlled-release systems and can be used as a biomedical material^[14]. KGM has gelation performance^[15], biocompatibility and biodegradability^[16]; thus, it has application prospects in foodstuffs^[17], drug carriers^[18], tissue scaffolds, absorbent materials^[19], etc. YiYuan et al.^[20] prepared a KGM/sodium alginate(SA)/graphene oxide (GO) solution by injection into a CaCl₂ solution under high-voltage static electricity assistance to fabricate microspheres and showed greatly efficiency improved ciprofloxacin (CPFX) loading and achieved a sustained release of CPFX. KGM can prevent the sudden release of a drug in the stomach, resulting in drug loss and toxicity and a low amount of release in the intestine. However, KGM, as a carrier for drug release, does not have good stability in water and is easy to disintegrate, which is not conducive to the continuous release of active substances, thus hindering its application.

  PGuA is the main component of terrestrial plant cell wall polysaccharides (pectin). It can be used for drug release or to immobilize cells or enzymes for the production of biomolecules. PGuA is a semirigid polymer that is insoluble in water and forms a rigid structure due to the presence of a galacturonic acid ring. Deepika Gupta et al.^[21] studied the electrospinning of PGuA and PVA. The PGuA solution produced only short fusiform fibers, and it was found that the addition of a small amount (10~30%) of high-molecularweight PVA resulted in the formation of continuous fibers and sodium dodecyl sulfate (SDS) as the surfactant. The surface tension can be lowered, the aggregation of PGuA can be prevented, and gelation can be suppressed. While PGuA is an important natural biopolymer, its potential has not been realized due to its anionic nature and rigid structure, which limits its processability. KGM with PGuA form an entangled network chain and impart elasticity to the blending solution, thereby increasing the mechanical strength and water solubility of the aerogel^[22].

  To compensate for the poor structure of KGM, the rigid characteristics of PGuA are used to form an entangled mesh chain with KGM to improve the mechanical strength and water solubility of aerogels. In this paper, a preparation method of KGM/PGuA aerogels was introduced, and its structure and properties were evaluated. The KGM/PGuA aerogels were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The effects of different component ratios on the rheological properties of the aerogels were investigated. The reaction mechanism of KGM/PGuA aerogel is shown in Scheme 1.

  Figure 1

  

  Figure 1.  KGM and PGuA interaction mechanism

  DownLoad: Full-Size Img PowerPoint

  2. EXPERIMENTAL

  2.1 Materials and chemicals

  PGuA (average molecular weight: 25000~50000) was purchased from Sigma-Aldrich. KGM (purity ≥ 90%; viscosity of a 1% solution at 30 ℃: ≥ 35, 000 mPa) was obtained from Hubei Yizhi Konjac Biotechnology Corp (Hubei, China). Sodium hydroxide and sodium dodecyl sulfate (SDS) were used as purchased.

  2.2 Method: preparation of KGM/PGuA aerogel

  First, 10% SDS (w/w of PGuA) and 4 mL of water were stirred until clear in a 50 ℃ water bath. Then, a certain amount of PGuA was added and stirred at 300 rpm for 1 h^[21]. Three milliliters of a 1 M NaOH solution was added and stirred for 3 min. Second, 1.2 g of KGM was dissolved in 100 mL of purified water and stirred at 500 rpm for 30 min at room temperature. Finally, the two solutions were mixed and stirred at 650 rpm for 5 min. A plate was filled with the mixture and frozen for 24 h in a freezer at −20 ℃; then, the mixture was vacuum-dried for 24 h to obtain the KGM/PGuA composite aerogel. The final ratios of PGuA to KGM were 0:8 (KGM), 1:8 (KGM/PGuA1), 2:8 (KGM/PGuA2), 3:8 (KGM/PGuA3), or 4:8 (KGM/PGuA4).

  2.3 Rheological properties of the solution

  The rheological properties of the different concentrations of KGM/PGuA composite gel (i.e., 0:8 (KGM), 1:8 (KGM/PGuA1), 2:8 (KGM/PGuA2), 3:8 (KGM/PGuA3), and 4:8 (KGM/PGuA4)) were investigated using a rotational rheometer (MCR301 Rheoplus), which consisted of a 50-mm parallel plate (PP50) with a plate-plate gap of 1 mm. The viscosity and stress of the KGM/PGuA gels were evaluated at 25 ℃, with shear rates ranging from 0.1 to 1000 s^-1. The temperature sweeps were operated over a temperature range from 25 to 85 ℃ at a rate of 5 ℃/min.

  2.4 Characterization of KGM/PGuA aerogels

  2.4.1   Scanning electron microscopy (SEM)

  The cross section of aerogel was observed with a Jsm-7500 f scanning electron microscope (Furebo International Co.). Samples were coated with gold, operated in high vacuum mode, and then scanned under an accelerating voltage of 15~20 kV.

  2.4.2   Infrared spectroscopy (FT-IR)

  The KGM/PGuA aerogels were characterized in KBr tablet form using an infrared spectrometer (BRUKER VERTEX 70; Madison, USA). The chemical structure of the KGM/PGuA composite aerogels and the interaction between the components were analyzed by infrared spectrometry (FT-IR). The spectral resolution was 4 cm^-1, and each spectrum was scanned in the range from 500 to 4000 cm^-1.

  2.4.3   X-ray diffraction (XRD)

  X-ray diffractograms of the aerogels were acquired by using a Bruker AXS X-ray (40 kV, 40 mA), and the scanning region of the diffraction ranged from 5° to 60° at a scan speed of 0.1 °/s.

  2.4.4   Statistical analysis

  The results of all analyses were expressed as averages with standard deviations of three independent experiments, and the OriginPro 9.0 was used to conduct the data analysis.

  3. RESULTS AND DISCUSSION

  3.1 Rheological behavior analysis of KGM/PGuA composite gel

  The relationship between the viscosity and shear stress of the KGM/PGuA composite aerogels in different proportions is presented in Fig. 1. It can be seen from the figure that, with increasing shear stress, the viscosity of KGM was larger than that of KGM/PGuA and the composite KGM/PGuA gel, but lower than those with ratios of 3:8 (KGM/PGuA3) and 4:8 (KGM/PGuA4), indicating that the addition of NaOH reduced the viscosity of KGM and that PGuA increased the viscosity of the composite gel and improved the molecular entanglement between KGM and PGuA molecules.

  Figure 1

  

  Figure 1.  Effect of different concentrations of PGuA on the shear stress of KGM/PGuA aerogels and viscosity

  DownLoad: Full-Size Img PowerPoint

  The relationship between the shear rate and viscosity of the KGM/PGuA composite aerogels is shown in Fig. 2. The viscosity of KGM and KGM/PGuA solution sharply decreased with increasing the shear rate, showing shearthinning behavior and indicating that the solution is a typical non-Newtonian pseudoplastic fluid^{[23, 24]}. The viscosity of the KGM/PGuA complex gel was higher than that of KGM, and the viscosity drastically decreased as the shear rate increased. The increasing ratio of PGuA increased the viscosity of KGM, which suggests that the rate of the viscosity declined in the high-shear-rate region because the random coil structure between the macromolecules in the KGM/PGuA composite gel was destroyed at a low shear rate; the molecules began to form a certain ordered arrangement, and the intermolecular forces were reduced. When the shear rate was further increased, a relatively stable and orderly structure was formed inside the composite gel, so the rate of viscosity decreased gradually.

  Figure 2

  

  Figure 2.  Effect of different concentrations of PGuA on the shear rate of KGM/PGuA gels and viscosity

  DownLoad: Full-Size Img PowerPoint

  Composite viscosity is one of the important parameters used to indicate the thermal sensitivity of hydrogels^[25]. As shown in Fig. 3, the viscosity of KGM and the composite aerogels exhibited an obvious temperature response above 60 ℃, which illustrated that PGuA and KGM were affected by temperature. However, when the ratio of KGM to PGuA is 4:8, the composite viscosity of the gel does not change much with increasing the temperature. This phenomenon may show that the interaction between KGM and PGuA led to stable physical cross-linking and that the KGM molecular chains in the composite hydrogels interacted with PGuA molecules by forming hydrogen bonds and physical entanglements.

  Figure 3

  

  Figure 3.  Effect of temperature on the composite viscosity of KGM/PGuA gels by PGuA with different mass ratios

  DownLoad: Full-Size Img PowerPoint

  3.2 Scanning electron microscopy analysis

  As shown in Fig. 4, the KGM aerogel and the KGM/PGuA composite aerogel were analyzed by electron microscopy (SEM). The KGM aerogel showed irregular structures with thin and broken pore walls. When PGuA was added, the pores of the KGM/PGuA aerogel became denser, and the surfaces became thicker and more complex, which helped to increase the specific surface area and mechanical strength and enhance the drug load ability. The small pores indicated that the PGuA increased the viscosity of the KGM/PGuA gel and that the hydroxyl groups in the PGuA interacted with the hydroxyl groups of KGM, and the interaction between molecules was enhanced to form a denser gel with better performance. Due to the ordered aggregation of polymer segments within the KGM/PGuA composite gel, stronger walls were formed. The interrelationship between the pores can be attributed to the formation of a crosslinked network in the gel. The composite gel had smaller pores that were more uniform in size and higher density than those of KGM, which revealed that the network connection between PGuA and KGM gel was enhanced.

  Figure 4

  

  Figure 4.  SEM images of (A) KGM and (B) KGM/PGuA at 100× magnification; SEM images of (a) KGM and (b) KGM/PGuA at 200× magnification

  DownLoad: Full-Size Img PowerPoint

  The infrared absorption spectra of KGM and KGM/PGuA aerogels in the wavelength range from 4000 to 400 cm^-1 were obtained, as shown in Fig. 5. The KGM characteristic peak of the -OH group was a broad and strong absorption peak in the wavelength range from 3500 to 3000 cm^-1, indicating that there was an abundance of -OH groups in the aerogel^{[26, 27]}. After adding PGuA, the KGM/PGuA aerogel, which had new properties, retained its characteristic absorption peak, and several new absorption peaks appeared at 954, 1244, and 1330 cm^-1. The absorption peak at 2924 cm^-1 increased with the addition of PGuA. The characteristic absorption peak of the ester νC-O-C bond had two absorption bands between 1330 and 1050 cm^-1, which indicated that an esterification reaction occurred between PGuA and KGM. The absorption peak near 1618 cm^-1 was obviously enhanced (tensile vibration) and represented C=O stretching vibration absorption, and the absorption peak with a higher wavenumber was compared. The new absorption peaks at 954 cm^-1 of KGM/PGuA indicated bonding between the PGuA and KGM molecules. These results indicate that PGuA successfully interacted with KGM.

  Figure 5

  

  Figure 5.  Infrared spectra of KGM and KGM/PGuA aerogels

  DownLoad: Full-Size Img PowerPoint

  3.5 X-ray diffraction analysis of the crystal structuresof different hydrogels

  The crystalline structures of KGM and KGM/PGuA aerogels and PGuA were evaluated by XRD. As shown in Fig. 6, broad diffusion and weak diffraction peaks at 21.74° were observed in the spectra of KGM aerogels, indicating the amorphous structure of KGM^[28]. PGuA showed two strong peaks at approximately 13.85° and 20.2°, which shows that PGuA has strong crystalline regions^{[29, 30]}. Compared with KGM, the KGM/PGuA aerogel also exhibited two significantly weak peaks at 2θ = 13.85° and 21.74°. These phenomena are attributed to the increased crystallization in the KGM/PGuA aerogels and the interaction of KGM with PGuA, which further reduced the aggregation of KGM and the helical structure of the molecular chain.

  Figure 6

  

  Figure 6.  XRD patterns of the KGM and KGM/PGuA aerogels and PGuA

  DownLoad: Full-Size Img PowerPoint

  4. CONCLUSION

  In this study, KGM/PGuA composite gels were successfully prepared by sol-gel via vacuum freeze-drying. The rheological properties of the KGM/PGuA aerogel indicated that PGuA enhanced the molecular interaction between the KGM/PGuA gels. The infrared spectroscopy and XRD results were mostly in agreement with the results of rheological properties, indicating that hydrogen bonding between PGuA and KGM has a certain effect on the gel properties. SEM images of the gel showed that PGuA improved the macrostructure of the gel and that the pores were denser. The above results support the improvement of the performance of KGM hydrogel by PGuA addition, which means that the gel has application prospects in drug loading.

  
  
• 1. [1]

     Ngo, H. V.; Tran, P. H. L.; Lee, B. J.; Tran, T. T. D. Development of film-forming gel containing nanoparticles for transdermal drug delivery. Nanotechnology 2019, 30, 415102−15. doi: 10.1088/1361-6528/ab2e29

  2. [2]

     Xu, Y.; Zhang, J. N.; Liu, X. Y.; Huo, P. C.; Zhang, Y.; Chen, H.; Tian, Q. F.; Zhang, N. MMP-2-responsive gelatin nanoparticles for synergistic tumor therapy. Pharm. Dev. Technol. 2019, 24, 1002−1013. doi: 10.1080/10837450.2019.1621899

  3. [3]

     Barclay, T. G.; Day, C. M.; Petrovsky, N.; Garg, S. Review of polysaccharide particle-based functional drug delivery. Carbohyd. Polym. 2019, 221, 94−112. doi: 10.1016/j.carbpol.2019.05.067

  4. [4]

     Moshkbar, H.; Arsalani, N.; Ghadimi, L. S. Synthesis of chitosan/gelatin granule containing amine derivated octa(ammonium chloride) substituted polyhedral oligomeric silsesquioxane and investigating its application as a drug carrier. Int. J. Polym. Mater. Po. 2019, 68, 836−843. doi: 10.1080/00914037.2018.1517345

  5. [5]

     Evranos, B.; Aycan, D.; Alemdar, N. Production of ciprofloxacin loaded chitosan/gelatin/bone ash wound dressing with improved mechanical properties. Carbohyd. Polym. 2019, 222, 115007−7. doi: 10.1016/j.carbpol.2019.115007

  6. [6]

     Boroojeni, F. R.; Mashayekhan, S.; Abbaszadeh, H. A. The controlled release of dexamethasone sodium phosphate from bioactive electrospun PCL/gelatin nanofiber scaffold. Iran J. Pharm. Res. 2019, 18, 111−124.

  7. [7]

     Yang, Y. F.; Meng, F. Y.; Li, X. H.; Wu, N. N.; Deng, Y. H.; Wei, L. Y.; Zeng, X. P. Magnetic graphene oxide-Fe₃O₄-PANI nanoparticle adsorbed platinum drugs as drug delivery systems for cancer therapy. J. Nanosci. Nanotechno. 2019, 19, 7517−7525. doi: 10.1166/jnn.2019.16768

  8. [8]

     Ambrosio, J. A. R.; Pinto, B. C. D.; Godoy, D. D.; Carvalho, J. A.; Abreu, A. D.; da Silva, B. G. M.; Leonel, L. D.; Costa, M. S.; Beltrame, M.; Simioni, A. R. Gelatin nanoparticles loaded methylene blue as a candidate for photodynamic antimicrobial chemotherapy applications in Candida albicans growth. J. Biomat. Sci. Polym E. 2019, 30, 1356−1373. doi: 10.1080/09205063.2019.1632615

  9. [9]

     Riyajan, S. A. Development of a novel pH-sensitive polymer matrix for drug encapsulation from maleated poly(vinyl alcohol) grafted with polyacrylamide. Polym. Bull. 2019, 76, 4585−4611. doi: 10.1007/s00289-018-2615-4

  10. [10]

      Jie, L. Y.; Lang, D.; Kang, X. Q.; Yang, Z. X.; Du, Y. Z.; Ying, X. Y. Superparamagnetic iron oxide nanoparticles/doxorubicin-loaded starch-octanoic micelles for targeted tumor therapy. J. Nanosci. Nanotechno. 2019, 19, 5456−5462. doi: 10.1166/jnn.2019.16548

  11. [11]

      Ting, G. L.; Chan, Y. Y.; Chaw, C. S. Mixed solvent system as binder for the production of silicified microcrystalline cellulose-based pellets. J. Appl. Polym. Sci. 2019, 136, 47924−9. doi: 10.1002/app.47924

  12. [12]

      Behera, S. S.; Ray, R. C. Nutritional and potential health benefits of konjac glucomannan, a promising polysaccharide of elephant foot yam. Amorphophallus konjac K. Koch: A review. Food Rev. Int. 2017, 33, 22−43. doi: 10.1080/87559129.2015.1137310

  13. [13]

      Huang, Y. C.; Yang, C. Y.; Chu, H. W.; Wu, W. C.; Tsai, J. S. Effect of alkali on konjac glucomannan film and its application on wound healing (vol 22, pg 737, 2015). Cellulose 2018, 25, 6819−6821. doi: 10.1007/s10570-018-2040-8

  14. [14]

      Neto, R. J. G.; Genevro, G. M.; Paulo, L. D.; Lopes, P. S.; de Moraes, M. A.; Beppu, M. M. Characterization and in vitro evaluation of chitosan/konjac glucomannan bilayer film as a wound dressing. Carbohyd. Polym. 2019, 212, 59−66. doi: 10.1016/j.carbpol.2019.02.017

  15. [15]

      Song, C. Z.; Lv, Y. K.; Qian, K. Y.; Chen, Y. L.; Qian, X. Preparation of konjac glucomannan-borax hydrogels with good self-healing property and pH-responsive behavior. J. Polym. Res. 2019, 26, 52−9. doi: 10.1007/s10965-019-1702-z

  16. [16]

      Wang, Y. X.; Chen, X.; Kuang, Y.; Xiao, M.; Su, Y. H.; Jiang, F. T. Microstructure and filtration performance of konjac glucomannan-based aerogels strengthened by wheat straw. Int. J. Low-Carbon. Tec. 2018, 13, 67−75.

  17. [17]

      Behera, S. S.; Ray, R. C. Konjac glucomannan, a promising polysaccharide of Amorphophallus konjac K. Koch in health care. Int J. Biol. Macromo. 2016, l92, 942-956.

  18. [18]

      Yuan, Y.; Yan, Z.; Mu, R. J.; Wang, L.; Gong, J. N.; Hong, X.; Haruna, M. H.; Pang, J. The effects of graphene oxide on the properties and drug delivery of konjac glucomannan hydrogel. J. Appl. Polym. Sci. 2017, 134, 45327−8. doi: 10.1002/app.45327

  19. [19]

      Yuan, Y.; Yang, D.; Mei, G.; Hong, X.; Wu, J.; Zheng, J.; Pang, J.; Yan, Z. Preparation of konjac glucomannan-based zeolitic imidazolate framework-8 composite aerogels with high adsorptive capacity of ciprofloxacin from water. Colloid Surf. A-Physicochem. Eng. Asp. 2018, 544, 187−195. doi: 10.1016/j.colsurfa.2018.01.042

  20. [20]

      Yuan, Y.; Xu, X. W.; Gong, J. N.; Mu, R. J.; Li, Y. Z.; Wu, C. H.; Pang, J. Fabrication of chitosan-coated konjac glucomannan/sodium alginate/graphene oxide microspheres with enhanced colon-targeted delivery. Int. J. Biol. Macromol. 2019, 131, 209−217. doi: 10.1016/j.ijbiomac.2019.03.061

  21. [21]

      Gupta, D.; Jassal, M.; Agrawal, A. K. Solution properties and electrospinning of poly(galacturonic acid) nanofibers. Carbohyd. Polym. 2019, 212, 102−111. doi: 10.1016/j.carbpol.2019.02.023

  22. [22]

      Abbott, D. W.; Hrynuik, S.; Boraston, A. B. Identification and characterization of a novel periplasmic polygalacturonic acid binding protein from Yersinia enterolitica. J. Mol. Biol. 2007, 367, 1023−1033. doi: 10.1016/j.jmb.2007.01.030

  23. [23]

      Liu, X. N.; Liu, S. C.; Xi, H. T.; Xu, J. J.; Deng, D. W.; Huang, G. H. Effects of soluble dietary fiber on the crystallinity, pasting, rheological, and morphological properties of corn resistant starch. Lwt-Food Sci. Technol. 2019, 111, 632−639. doi: 10.1016/j.lwt.2019.01.059

  24. [24]

      Liu, J. X.; Xu, B. J. A comparative study on texture, gelatinisation, retrogradation and potential food application of binary gels made from selected starches and edible gums. Food Chem. 2019, 296, 100−108. doi: 10.1016/j.foodchem.2019.05.193

  25. [25]

      Zhang, L. M.; Liu, Z. L.; Han, X. B.; Sun, Y.; Wang, X. Y. Effect of ethanol content on rheology of film-forming solutions and properties of zein/chitosan film. Int. J. Biol. Macromol. 2019, 134, 807−814. doi: 10.1016/j.ijbiomac.2019.05.085

  26. [26]

      Li, J. W.; Ma, J. W.; Chen, S. J.; He, J. M.; Huang, Y. D. Characterization of calcium alginate/deacetylated konjac glucomannan blend films prepared by Ca²⁺ crosslinking and deacetylation. Food Hydrocolloid. 2018, 82, 363−369. doi: 10.1016/j.foodhyd.2018.04.022

  27. [27]

      Hu, Y.; Tian, J.; Zou, J.; Yuan, X. Q.; Li, J.; Liang, H. S.; Zhan, F. C.; Li, B. Partial removal of acetyl groups in konjac glucomannan significantly improved the rheological properties and texture of konjac glucomannan and kappa-carrageenan blends. Int. J. Biol. Macromol 2019, 123, 1165−1171. doi: 10.1016/j.ijbiomac.2018.10.190

  28. [28]

      Wang, L.; Mu, R. J.; Yuan, Y.; Gong, J. N.; Ni, Y. S.; Wang, W. H.; Pang, J. Novel nanofiber membrane fabrication from konjac glucomannan and polydopamine via electrospinning method. J. Sol-Gel Sci. Techn. 2018, 85, 253−258. doi: 10.1007/s10971-017-4559-9

  29. [29]

      Wurfel, H.; Kayser, M.; Heinze, T. Non-aqueous solvent for efficient dissolution of polygalacturonic acid. Carbohyd. Polym. 2019, 207, 791−795. doi: 10.1016/j.carbpol.2018.12.036

  30. [30]

      Mishra, R. K.; Datt, M.; Banthia, A. K. Synthesis and characterization of pectin/PVP hydrogel membranes for drug delivery system. Aaps. Pharmscitech. 2008, 9, 395−403. doi: 10.1208/s12249-008-9048-6

• 

  Figure 1  KGM and PGuA interaction mechanism

  下载: 全尺寸图片 幻灯片
  

  Figure 1  Effect of different concentrations of PGuA on the shear stress of KGM/PGuA aerogels and viscosity

  下载: 全尺寸图片 幻灯片
  

  Figure 2  Effect of different concentrations of PGuA on the shear rate of KGM/PGuA gels and viscosity

  下载: 全尺寸图片 幻灯片
  

  Figure 3  Effect of temperature on the composite viscosity of KGM/PGuA gels by PGuA with different mass ratios

  下载: 全尺寸图片 幻灯片
  

  Figure 4  SEM images of (A) KGM and (B) KGM/PGuA at 100× magnification; SEM images of (a) KGM and (b) KGM/PGuA at 200× magnification

  下载: 全尺寸图片 幻灯片
  

  Figure 5  Infrared spectra of KGM and KGM/PGuA aerogels

  下载: 全尺寸图片 幻灯片
  

  Figure 6  XRD patterns of the KGM and KGM/PGuA aerogels and PGuA

  下载: 全尺寸图片 幻灯片
•