Antibiotic release controlled by sugarcane bagasse-based hydrogels as responsive carriers


 This work focuses on the transesterification of sugarcane bagasse cellulose (SBC) using tert-butyl acetoacetate (t-BAA) to obtain bagasse cellulose acetoacetate (BCAA), and the preparation of redox/pH dual-responsive hydrogels with cystamine dihydrochlorate (CYS). BCAA and cellulose hydrogels were comprehensively characterized with scanning electron microscopy (SEM), Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR), solubility and water retention. The results showed that BCAA was soluble in DMSO, and the degree of substitution (DS) ranged between 0.77 and 1.70, and the hydrogel had a certain water-retaining property. In addition, tetracycline hydrochloride (TH) was used as the model drug loaded in the hydrogel; and TH release can be manipulated or accelerated under reductive or weakly acidic conditions. According to the drug release kinetics analysis, suggested that the release mechanism of drug-loaded hydrogel was mainly driven by Fickian diffusion. The drug-loaded hydrogel also exhibited high antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Therefore, the dual-responsive and drug-loaded hydrogels have great potential in the applications associated with biomedicine.


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To further improve the performance of cellulose-based hydrogels, particularly for 108 those sugarcane bagasse-based ones which have not been fully explored yet, 6 temperature to obtain light yellow transparent viscous cellulose ionic solution. Under 146 the protection of nitrogen, DMAP (15 mg/g cellulose) was added at 110 ℃, followed 147 by dropwise-adding 14.8 g of t-BAA. The reactant was stirred for 3 h and then cooled.

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The product BCAA was precipitated by methanol, washed by Soxhlet extraction, and 149 then dried in a vacuum oven at 60 ℃ for 24 h. The morphology of sugarcane bagasse cellulose, bagasse cellulose acetoacetate and 162 hydrogel sample were observed using a scanning electron microscope (SEM, 163 S-3400N, Hitachi, Japan). The hydrogel was frozen at ultra-low temperature and then 164 freeze-dried. In order to analyze the internal structure of the hydrogel, the hydrogel 165 was broken under liquid nitrogen, and the cross section of the hydrogel was coated 166 with gold prior to SEM observation.

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The samples or products were ground into powder and mixed with KBr for Fourier  Hydrogen spectrum testing of BCAA samples using a 1 H nuclear magnetic resonance 174 (NMR) spectrometer (NMR, Avance III HD500, Bruker, Germany), 3 mg of BCAA 175 was dissolved in 0.6 mL of DMSO-d6 at 60 ℃, and the sample was scanned 64 times.   Where Wdrug-loaded is the amount of drug loaded into hydrogel, Wdry-hydrogel is the quality 208 of lyophilized hydrogel and Wdrug-added is the initial total amount of the drug.

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The drug-loaded hydrogel was placed in a flask and 10 mL buffer solutions with 210 different pH or GHS contents were added and put into a thermostatic water bath 211 oscillator for drug release (37 ℃, 100 rpm). At the set time, 4 mL of drug released 212 solution were removed and the same volume of buffer solution was added. The 213 solution was analyzed by ultraviolet spectrophotometer. Equation (5) and (6) were 214 used to calculate the cumulative release and release rate.

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Cumulative release(%) = 10 Where Cn is the concentration of TH released when sampled at the n times and Wdrug 218 is the amount of TH released during the time period from tn-1 to tn. 219 Drug release kinetics 220 To reveal the mechanism and kinetics of drug release from hydrogels, drug release 221 data were fitted to various kinetic models, which are the zero order model (Eq. (7)),  The samples were further characterized by FTIR (Fig. 1a). Compared with SBC, the acetoacetyl groups. After the cellulose hydrogel was loaded with drugs, it was also 269 subjected to FTIR analysis (Fig. 1b). 1579 cm -1 and 1614 cm -1 are the characteristic 270 absorption peaks corresponding to the carbonyl group on ring a and ring c of TH.

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Comparing the infrared spectra before and after the drug loading, it was found that The crystal structures of BC, SBC and BCAA were analyzed by XRD; whereas, the 291 DS of BCAA was quantified based on the results obtained from 1 H NMR (Fig. 2) of BCAA was completely transformed into cellulose II crystal structure (Fig. 2a), and 298 the crystallinities of SBC and BCAA were 80.8% and 11.5%, respectively. This    decreased with the increase of BCAA concentration (Fig. 4b). The reason may be that The hydrogel exhibited an excellent sustained release property, clearly demonstrating 358 the good feasibility of loading drug into hydrogel network scaffolds for sustained 359 release. When pH was adjusted to 5.0, the total drug release of cellulose hydrogel 360 increased, and reached the maximum sustained release within the first 7 h. After the 361 addition of 10 mM GSH, the drug release rate of cellulose hydrogel was significantly 362 accelerated (Fig. 4d), and 75% of the total drug load was released within 6.5 h. And and Korsmeyer-Peppas models (Fig. 5 and 6). According to the fitting results of drug 383 release data of BCAA/CYS hydrogel in different conditions (Table 2), the correlation 384 coefficient R 2 of the Korsmeyer-Peppas model was higher than those from other 385 models, which indicated that the drug release kinetics of BCAA/CYS hydrogel 386 follows the Korsmemeyer-Peppas model well. In addition, the exponent (n) in Table 2 387 suggested that the release mechanism of BCAA/CYS hydrogel is mainly driven by 388 Fickian diffusion.  conditions, but that the antibacterial activities were not sufficiently high. However, 435 when pH was reduced or GSH was added, the growth inhibition rates increased. After