A novel pH‐ and thermo‐sensitive PVP/CMC semi‐IPN hydrogel: Swelling,phase behavior,and drug release study

Poly(N‐vinyl‐pyrrolidone) (PVP) hydrogel has been considered as a very interesting and promising thermosensitive material. The most vital shortcoming of PVP hydrogel as thermosensitive material is that it does not exhibit thermosensitivity under usual conditions. In this work, semi‐interpenetrating polymer network (semi‐IPN) hydrogels based on PVP and carboxymethylcellulose (CMC) were prepared. The volume phase transition temperature (VPTT) of the hydrogels was determined by swelling behavior and differential scanning calorimetry (DSC). The results showed that the VPTT was significantly dependent on CMC content and the pH of the swelling medium. The amount of CMC in the semi‐IPN hydrogels was 0.050, 0.075, and 0.100 g, the VPTT in buffer solution of pH 1.2 was 29.9 °C, 27.5 °C and 24.5 °C, respectively. In addition, the VPTT occurred in buffer solution of pH 1.2, but did not appear in alkaline medium. Bovine serum albumin (BSA) as a model drug was loaded and the in vitro release studies were carried out in different buffer solutions and at different temperatures. The results of this study suggest that PVP/CMC semi‐IPN hydrogels could serve as potential candidates for protein drug delivery in the intestine. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1749–1756, 2010     

Konjac glucomannan‐graft‐acrylic acid hydrogels containing azo crosslinker for colon‐specific delivery

In this article, the synthesis and characterization of novel hydrogel systems designed for colon‐targeting drug delivery are reported. The gels were composed of konjac glucomannan, copolymerized with acrylic acid, and crosslinked by the aromatic azo agent bis(methacryloylamino)‐azobenzene. The influence of various parameters on the dynamic and equilibrium swelling ratios (SRs) of the hydrogels was investigated. It is shown that the SR was inversely proportional to the grafting degree of acrylic acid and the content of bis(methacryloylamino)‐azobenzene. The dependence of SR on the pH indicates that obtained hydrogels are potential for drug delivery to colon. It was possible to modulate the degree of swelling and the pH sensitivity of the gels by changing crosslinking density of the polymer. The main chain of hydrogels can be degraded by β‐glycosidase which is abundant in colon. They can be in vitro degraded for 73% in a month by Cereflo® and 86% in 20 days by Mannaway25L. We have also prepared the hydrogels that loaded with bovine serum albumin about 1.5%, 3%, 9%, and 20% by weight. In vitro release of model drug bovine serum albumin was studied in the presence of Mannaway25L or Fungamyl®800L in pH 7.4 phosphate buffer at 37 °C. The drug release can be controlled by the biodegradation of the hydrogels. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4370–4378, 2004     

Thermoresponsive drug controlled release from chitosan‐based hydrogel embedded with poly(N‐isopropylacrylamide) nanogels

A facile synthetic strategy was developed for the preparation of thermoresponsive nanocomposite hydrogels comprising crosslinked chitosan (CS) networks and poly(N‐isopropylacrylamide) [p(NIPAAm)] nanogels. First, thermoresponsive p(NIPAAm) nanogels were synthesized via emulsion polymerization. The p(NIPAAm) nanogels were introduced into methacrylamide CS (MC) solution and the free‐radical initiated crosslinking reaction of MC produced nanogel‐embedded hydrogels. The last step involves the loading of the antibacterial model drug levofloxacin (LFX) into the prepared nanocomposite hydrogels by allowing the preformed hydrogels to swell to equilibrium in the drug's aqueous solution. The integration of p(NIPAAm) nanogel into CS networks facilitates thermoresponsive release of LFX with an enhancement of the drug‐loading capacity within the hydrogel. Notably, thermoresponsive drug‐release was achieved without unwarranted modification of the hydrogel's dimension and shape, although an increase in temperature caused the collapse of the p(NIPAAm) nanogels. The thermoresponsive property of the investigated nanocomposite hydrogel is beneficial and may offer broad opportunities for drug temperature‐triggered release for clinical applications. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1907–1914     

Synthesis,characterization, and evaluation of enzymatically degradable poly(N‐isopropylacrylamide‐co‐acrylic acid) hydrogels for colon‐specific drug delivery

The enzymatically degradable poly(N‐isopropylacrylamide‐co‐acrylic acid) hydrogels were prepared using 4,4^′‐bis(methacryloylamino)azobenzene (BMAAB) as the crosslinker. It was found that the incorporated N‐isopropylacrylamide (NIPAAm) monomer did not change the enzymatic degradation of hydrogel, but remarkably enhanced the loading of protein drug. The hydrogels exhibited a phase transition temperature between 4°C (refrigerator temperature) and 37°C (human body temperature). Bovine serum albumin (BSA) as a model drug was loaded into the hydrogels by soaking the gels in a pH 7.4 buffer solution at 4°C, where the hydrogel was in a swollen status. The high swelling of hydrogels at 4°C enhanced the loading of BSA (loading capability, ca. 144.5 mg BSA/g gel). The drug was released gradually in the pH 7.4 buffer solution at 37°C, where the hydrogel was in a shrunken state. In contrast, the enzymatic degradation of hydrogels resulted in complete release of BSA in pH 7.4 buffer solution containing the cecal suspension at 37°C (cumulative release: ca. 100 mg BSA/g gel after 4 days). Copyright © 2008 John Wiley & Sons, Ltd.     

pH and reduction dual‐stimuli‐responsive PEGDA/PAMAM injectable network hydrogels via aza‐michael addition for anticancer drug delivery

A pH and reduction dual‐stimuli‐responsive PEGDA/PAMAM injectable network hydrogel containing “acetals” as pH‐sensitive groups and “disulfides” as reducible linkages was designed and synthesized via aza‐Michael addition reaction between PAMAM and PEGDA diacrylates. The pore size and swelling ratio of hydrogels was varied from 14 ± 3 to 19 ± 4 μm and 214 ± 13 to 300 ± 19 μm, respectively, with varying ethylene glycol repeating units in diacrylates. The swelling ratio of PEGDA/PAMAM network hydrogel increased with increase in the molecular weight of PEG and with decrease in pH. The presence of different cationizable amino‐functionalities in PEGDA/PAMAM network hydrogel helped to enhance the swelling ability of hydrogel under the acidic conditions. The continuous increase in metabolically active live HeLa cells with time in MTT assay implied biocompatibility/noncytotoxicity of the synthesized PEGDA/PAMAM injectable network hydrogel. Furthermore, the prepared PEGDA/PAMAM hydrogel showed higher degradation at lower pH and at higher concentration of DTT. The burst release of doxorubicin from PEGDA/PAMAM hydrogel under the environment of the lower pH and in presence of DTT compared to the release at normal physiological pH and in absence of DTT suggested the potential ability of this model hydrogel system for targeted and selective anticancer drug release at tumor tissues. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 2080–2095     

Three‐dimensional microfabrication of protein hydrogels via two‐photon‐excited thiol‐vinyl ester photopolymerization

Engineering three‐dimensional (3D) hydrogels with well‐defined architectures has become increasingly important for tissue engineering and basic research in biomaterials science. To fabricate 3D hydrogels with (sub)cellular‐scale features, two‐photon polymerization (2PP) shows great promise although the technique is limited by the selection of appropriate hydrogel precursors. In this study, we report the synthesis of gelatin hydrolysate vinyl esters (GH‐VE) and its copolymerization with reduced derivatives of bovine serum albumin (acting as macrothiols). Photorheology of the thiol‐ene copolymerization shows a much more rapid onset of polymerization and a higher end modulus in reference to neat GH‐VE. This allowed 2PP to provide well‐defined and stable hydrogel microstructures. Efficiency of the radical‐mediated thiol‐vinyl ester photopolymerization allows high 2PP writing speed (as high as 50 mm s^?1) with low laser power (as low as 20 mW). MTT assays indicate negligible cytotoxicities of the GH‐VE macromers and of the thiol‐ene hydrogel pellets. Osteosarcoma cells seeded onto GH‐VE/BSA hydrogels with different macromer relative ratios showed a preference for hydrogels with higher percentage of GH‐VE. This can be attributed both to a favorable modulus and preferable protein environment since gelatin favors cell adhesion and albumin incurs nonspecific binding. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 4799–4810     

Biodegradable thermo‐ and pH‐responsive hydrogels for oral drug delivery

In this article, novel smart hydrogels based on biodegradable pH sensitive poly(L ‐glutamic acid‐g‐2‐hydroxylethyl methacrylate) (PGH) chains and temperature‐sensitive hydroxypropylcellulose‐g‐acrylic acid (HPC‐g‐AA) segments were designed and synthesized. The influence of pH and temperature on the equilibrium swelling ratios of the hydrogels was discussed. The optical transmittance of the hydrogels was also changed as a function of temperature, which reflecting that the HPC‐g‐AA part of the hydrogels became hydrophobic at the temperature above the lower critical solution temperature (LCST). At the same time, the LCST of the hydrogels had a visible pH‐dependent behavior. Scanning electron microscopic analysis revealed the morphology of the hydrogels before and after enzymatic degradation. The biodegradation rate of the hydrogels was directly related to the PGH content and the pH value. The in vitro release of bovine serum albumin from the hydrogels were investigated. The release profiles indicated that both the HPC‐g‐AA and PGH contents played important roles in the drug release behaviors. These results show that the smart hydrogels seem to be of great promise in pH–temperature oral drug delivery systems. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Drug‐Loaded Elastin‐Like Polypeptide–Collagen Hydrogels with High Modulus for Bone Tissue Engineering

Emphasizing the role of hydrogel stiffness and cellular differentiation, this study develops collagen and elastin‐like polypeptide (ELP)–based bone regenerative hydrogels loaded with recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and doxycycline with mechanical properties suitable for osteogenesis. The drug‐incorporated collagen–ELP hydrogels has significantly higher modulus of 35 ± 5 kPa compared to collagen‐only hydrogels. Doxycycline shows a bi‐phasic release with an initial burst release followed by a gradual release, while rhBMP‐2 exhibits a nearly linear release profile for all hydrogels. The released doxycycline shows anti‐microbial activity against Pseudomonas aeruginosa, Streptococcus sanguinis, and Escherichia coli. Microscopic observation of the hydrogels reveals their interconnected, macroporous, 3D open architecture with pore diameters between 160 and 400 µm. This architecture supports human adipose–derived stem cell attachment and proliferation from initial days of cell seeding, forming a thick cellular sheath by day 21. Interestingly, in collagen and collagen–ELP hydrogels, cell morphology is elongated with stretched slender lamellipodial formation, while cells assemble as spheroidal aggregates in crosslinked as well as drug‐loaded hydrogels. Osteogenic markers, alkaline phosphatase and osteocalcin, are expressed maximally for drug‐loaded hydrogels compared to those without drugs. The drug‐loaded collagen–ELP hydrogels are thus promising for combating bacterial infection and promoting guided bone regeneration.     

pH/temperature double responsive behaviors and mechanical strength of laponite‐crosslinked poly(DEA‐co‐DMAEMA) nanocomposite hydrogels

A nanocomposite (NC) hydrogel crosslinked by inorganic Laponite XLG was successfully synthesized via in situ free radical polymerization of monomers N,N‐diethylacrylamide and (2‐dimethylamino) ethyl methacrylate (DMAEMA). Polymerization was carried out at room temperature due to the accelerating effect of DMAEMA. The as‐prepared hydrogels displayed controlled transformation in optical transmittance and volume in response to small diversification of environmental factors, such as temperature and pH. The compressive strength of swollen D_6:1G₆ hydrogels was as high as 2219 kPa while compressive strain was 95%. Cyclic compression measurement exhibited good elastic properties of NC hydrogels. This work provides a facile method for fabricating stimuli‐responsive hydrogels with superior mechanical property. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 876–884     

Synthesis and rheological investigation of self‐healable deferoxamine grafted alginate hydrogel

Deferoxamine grafted alginate (SA‐DFA) was successfully synthesized via amidation of sodium alginate with deferoxamine mesylate as determined by H‐NMR and elemental analysis. SA‐DFA with different graft yield was obtained by adjusting the ratio of sodium alginate and deferoxamine mesylate. It was found that aqueous solution of SA‐DFA could form hydrogel spontaneously due to hydrogen bonding interactions, which also endowed the SA‐DFA hydrogel with self‐healing capability. The healing efficiency of SA‐DFA hydrogels ranged from 53.64 to 90.16%. In addition, surface morphologies of SA‐DFA hydrogels before/after self‐healing process were demonstrated by SEM images. We anticipated that such self‐healable alginate hydrogel would be applied in the field of wound healing. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017 , 55, 856–865     

Network structure and swelling–shrinking behaviors of pH‐sensitive poly(acrylamide‐co‐itaconic acid) hydrogels

pH‐sensitive poly(acrylamide‐co‐itaconic acid) [P(AAm/IA)] hydrogels were prepared by radiation induced copolymerization of acrylamide (AAm) and itaconic acid (IA) at various ratios. Swelling and shrinking behaviors of these hydrogels were found greatly dependent on the composition of the hydrogel and pH of the buffer solution. The basic structural parameters of the P(AAm/IA) networks such as the molecular weight between crosslinks (M _c) and polymer–solvent interaction parameter (χ) were also determined using the modified Flory‐Rehner equations. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 2586–2594, 2004     

Zr(IV)‐Crosslinked Polyacrylamide/Polyanionic Cellulose Composite Hydrogels with High Strength and Unique Acid Resistance

Recently, metal coordination has been widely utilized to fabricate high‐performance hydrogels, but conventional metal‐based hydrogels face some drawbacks, such as staining or acid lability. In the present study, a novel kind of colorless Zr(IV)‐crosslinked polyacrylamide/polyanionic cellulose (PAM/PAC) composite hydrogel with unique acid resistance was constructed via acrylamide polymerization in a PAC solution, followed by posttreatment in a zirconium oxychloride (ZrOCl₂) solution. The prepared gels were characterized in terms of Fourier transform infrared spectroscopy, scanning electron microscopy, and tensile and compressive mechanics, as well as acid resistance. Inside the gels, the synergistic action of hydrogen bonding and Zr(IV) coordination is responsible for their improved mechanical properties and good energy dissipation ability. One hydrogel with nearly 90 wt % of water content can sustain approximately 5 MPa of compression stress at 90% strain without damage. Both microscopic network structures and macroscopic mechanics demonstrate facile adjustability via changing the PAC dosages in polymerization and/or ZrOCl₂ concentrations in posttreatment. Moreover, the gels present unexpected acid resistance due to the strong Zr(IV) coordination with PAC, demonstrating their potential application as hydrogel electrolytes in supercapacitors. The current work provides a new approach to fabricate metal coordination‐based high strength, colorless hydrogels with acid resistance. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 981–991     

Preparation and properties of poly(N‐isopropylacrylamide)/poly(N‐isopropylacrylamide) interpenetrating polymer networks for drug delivery

A novel poly(N‐isopropylacrylamide) (PNIPA)/PNIPA interpenetrating polymer network (IPN) was synthesized and characterized. In comparison with conventional PNIPA hydrogels, the shrinking rate of the IPN hydrogel increased when gels, swollen at 20 °C, were immersed in 50 °C water. The phase‐transition temperature of the IPN gel remained unchangeable because of the same chemical constituent in the PNIPA gel. The reswelling kinetics were slower than those of the PNIPA hydrogel because of the higher crosslinking density of the IPN hydrogel. The IPN hydrogel had better mechanical strength because of its higher crosslinking density and polymer volume fraction. The release behavior of 5‐fluorouracil (5‐Fu) from the IPN hydrogel showed that, at a lower temperature, the release of 5‐Fu was controlled by the diffusion of water molecules in the gel network. At a higher temperature, 5‐Fu inside the gel could not diffuse into the medium after a burst release caused by the release of the drug on the surface of the gel. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1249–1254, 2004     

Synthesis,characterization, and drug release behaviors of a novel thermo‐sensitive poly(N‐acryloylglycinates)

In this study, a novel thermo‐sensitive poly(N‐acryloylglycinates) was prepared in order to get a potential drug release carrier. The corresponding monomers and the polymers were characterized with Fourier‐transform infrared (FTIR) and ¹H NMR. The thermo‐sensitivity of the poly(N‐acryloylglycinates) was evaluated by measuring their lower critical solution temperatures (LCST) in water, inorganic salt solution, and different pH solutions. The results indicated that poly(N‐acryloylglycine methyl ester) (NAGME) and poly(N‐acryloylglycine ethyl ester) (NAGEE) exhibit a reversible thermo‐sensibility in their aqueous solutions at 61.5 and 12.5°C, respectively. However, no thermo‐sensitive behavior of poly(N‐acryloylglycine propyl ester) (NAGPE) was found due to its over hydrophobicity. The swelling studies on hydrogels were carried out at different temperatures, in different pH, and inorganic salt solutions. The hydrogels showed a remarkable phase transition at about 35°C with changing temperature. The release rate of caffeine from the thermo‐sensitive hydrogel was apparently decreased as the crosslinker content increased and temperature decreased. Seventy five percent caffeine from the polymeric hydrogel with 5% NMBA (N, N‐methylenebis(acrylamide)) was released at room temperature within 240 min, whereas 95.4% caffeine diffused into the medium at 37°C. Copyright © 2009 John Wiley & Sons, Ltd.     

Double‐crosslinked reversible redox‐responsive hydrogels based on disulfide–thiol interchange

We present novel redox‐responsive hydrogels based on poly(N‐isopropylacrylamide) or poly(acrylamide), consisting of a reversible disulfide crosslinking agent N,N′‐bis(acryloyl)cystamine and a permanent crosslinking agent N,N′‐methylenebisacrylamide for microfluidic applications. The mechanism of swelling/deswelling behavior starts with the cleavage and reformation of disulfide bonds, leading to a change of crosslinking density and crosslinking points. Raman and ultraviolet‐visible spectroscopy confirm that conversion efficiency of thiol–disulfide interchange up to 99%. Rheological analysis reveals that the E modulus of hydrogel is dependent on the crosslinking density and can be repeatedly manipulated between high‐ and low‐stiffness states over at least 5 cycles without significant decrease. Kinetic studies showed that the mechanical strength of the gels changes as the redox reaction proceeds. This process is much faster than the autonomous diffusion in the hydrogel. Moreover, cooperative diffusion coefficient (D_coop) indicates that the swelling process of the hydrogel is affected by the reduction reaction. Finally, this reversibly switchable redox behavior of bulky hydrogel could be proven in microstructured hydrogel dots through short‐term photopatterning process. These hydrogel dots on glass substrates also showed the desired short response time on cyclic swelling and shrinking processes known from downsized hydrogel shapes. Such stimuli‐responsive hydrogels with redox‐sensitive crosslinkers open a new pathway in exchanging analytes for sensing and separating in microfluidics applications. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 2590–2601     

Lactose‐containing hydrogels for enzyme stabilization

A lactose‐containing monomer, N‐(2‐lactosylethyl)acrylamide, was synthesized and polymerized with N‐hydroxyethyl acrylamide and 1 wt % of N, N'‐methylenebis(acrylamide) and potassium persulfate as the initiator to produce hydrogels. The weight percent of N‐(2‐lactosylethyl)acrylamide were increased from 0 to 100% in increments of 10%. Hydrogels were successfully produced with up to 90 wt % of N‐(2‐lactosylethyl)acrylamide. Gelation was confirmed by inverted vial tests and rheology measurements. The as‐prepared hydrogels were used for papain stabilization against heat burden and papain that was loaded into hydrogels showed 45% more activity after heating as compared to papain that was heated without hydrogel stabilization. This hydrogel stabilization technique has potential applications in preserving enzyme activity. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2507–2514     

3‐D Interdigitated electrodes for uniform stimulation of electro‐responsive hydrogels for biomedical applications

Stimuli‐responsive hydrogels are continuing to increase in demand in biomedical applications. Occluding a blood vessel is one possible application which is ideal for a hydrogel because of their ability to expand in a fluid environment. However, typically stimuli‐responsive hydrogels focus on bending instead of radial uniform expansion, which is required for an occlusion application. This article focuses on using an interdigitated electrode device to stimulate an electro‐responsive hydrogel in order to demonstrate a uniform swelling/deswelling of the hydrogel. A Pluronic‐bismethacrylate (PF127‐BMA) hydrogel modified with hydrolyzed methacrylic acid, in order to make it electrically responsive, is used in this article. An interdigitated electrode device was manufactured containing Platinum electrodes. The results in this paper show that the electrically biased hydrogels deswelled 230% more than the non‐biased samples on average. The hydrogels deswelled uniformly and showed no visual deformations due to the electrical bias. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013 , 51, 1523–1528     

Synthesis,characterization and evaluation of semi‐IPN hydrogels consisted of poly(methacrylic acid) and guar gum for colon‐specific drug delivery

The semi‐IPN hydrogels consisting of poly(methacrylic acid) and guar gum (GG) are prepared at room temperature using water as solvent. 5‐aminosalicylic acid (5‐ASA) is entrapped in the hydrogel in the synthesis of hydrogel and all entrapment efficiencies are found above 85%. The hydrogel shows excellent pH‐sensitivity. It exhibited minimum swelling in an acidic pH medium through the formation of a complex hydrogen‐bonded structure and maximal swelling due to the electrostatic repulsion due to the ionization of the carboxylic groups in pH 7.4 medium. The degradation in vitro shows that the degree of degradation (R%) depended on the concentration of cross‐linking agent and content of GG. The hydrogel shows a minimum release of 5‐ASA due to the complex hydrogen bonded structure of the hydrogels in the medium of pH 2.2. The enzymatic degradation of hydrogels by cecal bacteria can accelerate the release of 5‐ASA entrapped in the hydrogel in pH 7.4 medium. Copyright © 2007 John Wiley & Sons, Ltd.     

Positron annihilation studies on radiation‐crosslinked poly(N‐isopropylacrylamide) hydrogels

The temperature‐sensitive poly(N‐isopropylacrylamide) hydrogels, prepared by γ and electron‐beam (EB) irradiation, were studied using positron annihilation lifetime spectroscopy (PALS). The effect of water content in the hydrogel on the ortho‐positronium (o‐Ps) lifetime and intensity was investigated. The observed positronium lifetime suggests microstructural differences between γ‐ and EB‐synthesized hydrogels. The distribution in positronium lifetime indicates nonhomogeneity in the distribution of free‐volume holes in EB‐synthesized hydrogels. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 3462–3466, 2000     

Chitosan‐Based Thermo/pH Double Sensitive Hydrogel for Controlled Drug Delivery

A series of thermo/pH sensitive N‐succinyl hydroxybutyl chitosan (NSHBC) hydrogels with different substitution degrees of succinyl are prepared for drug delivery. Rheology analysis shows that the gelation temperature of NSHBC hydrogels is 3.8 °C higher than that of hydroxybutyl chitosan (HBC) hydrogels. A model drug bovine serum albumin (BSA) is successfully loaded and released. NSHBC hydrogels show excellent pH sensitivity drug release behaviors. After incubation for 24 h, 93.7% of BSA is released from NSHBC hydrogels in phosphate buffer saline (PBS) (pH 7.4), which is significantly greater than that of 24.6% at pH 3.0. In contrast, the release rate of BSA from HBC is about 70.0% at pH 3.0 and 7.4. Thus, these novel hydrogels have the prominent merits of high adaptability to soluble drugs and pH sensitivity triggered release, indicating that NSHBC hydrogels have promising applications in oral drug delivery.