pH-responsive Hydrogels Research Articles

Flexible wood-based pH-responsive hydrogel excipient for rapid recovery of infected wounds

Infected wounds heal slowly and may become pus-filled, bloated, and feverish if left untreated. Wood is an ideal substrate for improving the mechanical properties of composites and increasing the number of loading positions because of the unique structure and excellent properties. In this work, after chemically eliminating some of the lingin and hemicellulose from wood, a flexible wood was obtained. The freeze-thaw approach was used to create a pH-responsive flexible wood-based hydrogel (FTS-G@PC) comprising polyvinyl alcohol (PVA) and chitosan (CS) crosslinked wrapped gentamicin (GS). It is particularly biocompatible because to the natural wood employed and the physically cross-linked hydrogel generated by cyclic freezing, and the pH responsiveness is more relevant for septic wounds. Results demonstrated that the surface stiffness of the modified wood was significantly decreased closer to the skin and that the flexibility and increased adhesion permitted excellent skin adaptation. In vitro experiments had revealed that FTS-G@PC had high cytocompatibility, pH-responsiveness, and a strong antibacterial. The dressing promoted wound recovery faster in a mouse model of infected wounds. Therefore, FTS-G@PC is one of the promising and excellent renewable dressings.

A novel pH-responsive hydrogel system based on Prunus armeniaca gum and acrylic acid: Preparation and evaluation as a potential candidate for controlled drug delivery

pH-responsive hydrogels have become effective and attractive materials for the controlled release of drugs at pre-determined destinations. In the present study, a novel hydrogel system based on Prunus armeniaca gum (PAG) and acrylic acid (AA) was prepared by a free radical mechanism using N, N-methylene bisacrylamide (MBA) as cross-linker and potassium persulfate (KPS) as initiator. A series of hydrogels varying PAG, AA, and MBA concentration was developed to determine the impact of these components. Formulated hydrogels were characterized for pH-responsive swelling, drug release, gel content, and porosity. Structural analysis was performed by FTIR, XRD, and SEM analysis. TGA study was applied to assess thermal stability. Oral acute toxicity and in vivo drug release were performed in rabbits. Hydrogels exhibited pH-dependent swelling and drug release. Swelling, drug loading and release, and porosity increased by increasing PAG and AA concentration while decreased by increasing MBA. The gel content of formulations was increased by increasing all three components. FTIR studies confirmed the development of copolymeric networks and the loading of drug. XRD studies revealed that hydrogels were amorphous, and the crystalline drug was changed into an amorphous form during loading. TGA results indicated that hydrogels were stable up to 600 °C. Acute oral toxicity results confirm that hydrogels were nontoxic up to a dose of 2 g/kg body weight in rabbits. The pharmacokinetic evaluation revealed that hydrogels prolonged the availability of the drug and the peak plasma concentration of the drug was obtained in 6 h as compared to the oral solution of the drug. Tramadol hydrochloride (THC) was used as a model drug. Hence, pH-responsive swelling and release, nontoxic nature and improved pharmacokinetics support that PAG-based hydrogels may be considered as potential controlled-release polymeric carriers.

Development and assessment of carboxymethyl tamarind kernel gum-based pH-responsive hydrogel for release of diclofenac sodium

The current research work focuses on the fabrication of carboxymethyl tamarind kernel gum/polyvinylpyrrolidone/polyacrylamide (CMTKG/PVP/PAM) based hydrogel and its loading was done with diclofenac sodium drug (DS) to obtain smart pH-responsive hydrogels. In addition, the effect of concentration of cross-linker- N, N′-methylene bis(acrylamide) (MBA), biopolymer (CMTKG), as well as initiator- potassium persulphate (KPS) on the swelling behavior of smart hydrogel was also analyzed. The synthesized hydrogels were characterized using Scanning Electron Microscopy (SEM), Powder X-ray Diffraction (PXRD), Thermogravimetry Analysis (TGA), and Attenuated Total Reflection-Fourier Transform Infrared spectroscopy (ATR-FTIR). ATR-FTIR confirms the successful formation of hydrogels, while PXRD and SEM indicate the amorphous and porous nature of the polymeric network. The TGA results indicate higher thermal stability for DS-loaded hydrogel than unloaded hydrogel. However, sol–gel analysis shows a rise in gel fraction, with increased concentrations of CMTKG, MBA, and KPS. The swelling ratio as well as the release of DS were found to be higher under slightly alkaline conditions. The result of drug loading and release indicates that PVP increases drug loading (%) and release (%). The drug release behavior of DS-loaded hydrogel follows the Fickian mechanism of diffusion with the Korsmeyer-Peppas model as the best-fitted one. The synthesized DS-loaded CMTKG/PVP/PAM hydrogels could be a promising substitute for prolonged delivery of sparingly soluble DS in pH 7.4.

Synthesis and Evaluation of Functionalized Polyurethanes for pH-Responsive Delivery of Compounds in Chronic Wounds.

Chronic wounds, depending on the bacteria that caused the infection, can be associated with an extreme acidic or basic pH. Therefore, the application of pH-responsive hydrogels has been instigated for the delivery of therapeutics to chronic wounds. Herein, with the aim of developing a flexible pH-responsive hydrogel, we functionalized hydrophilic polyurethanes with either cationic (polyethylene imine) or anionic (succinic anhydride) moieties. A comprehensive physicochemical characterization of corresponding polymers was carried out. Particularly, when tested in aqueous buffers, the surface charge of hydrogel films was closely correlated with the pH of the buffers. The loading of the cationic and anionic hydrogel films with various compound models (bromophenol blue; negatively charged or Pyronin Y; positively charged) showed that the electrostatic forces between the polymeric backbone and the compound model will determine the ultimate release rate at any given pH. The potential application of these films for chronic wound drug delivery was assessed by loading them with an antibiotic (ciprofloxacin). In vitro bacterial culturing was performed using Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Results showed that at the same drug dosage, different release profiles achievable from cationic and anionic polyurethanes can yield different degrees of an antibacterial effect. Overall, our results suggest the potential application of cationic and anionic hydrophilic polyurethanes as flexible pH-responsive materials for the delivery of therapeutics to chronic wounds.

Development and characterization of pH responsive sodium alginate hydrogel containing metal-phenolic network for anthocyanin delivery

Favorable hydrogels can be used as a material to deliver bioactive molecules and improve the stability of bioactive substances, while their safety needs to be improved. In this study, protocatechuic acid (PCA) and Fe3+ were rapidly self-assembled to form a metal-phenolic network under different pH conditions, and then sodium alginate (SA) was added to prepare the SA/PCA/Fe hydrogel without adding other chemical reagents. The structural characteristic of SA/PCA/Fe hydrogel was characterized by infrared spectroscopy, X-ray diffraction analysis and scanning electron microscopy. The results showed that the structures of SA/PCA/Fe hydrogels prepared at different pH values were significantly different. The texture analysis, water-holding measurement and rheological analysis indicated that the SA/PCA/Fe hydrogel showed higher gel strength, water holding capacity and storage modulus. Thermogravimetric analysis illuminated that the SA/PCA/Fe hydrogel enhanced the thermal stability of free anthocyanins through encapsulating anthocyanins. Moreover, in vitro simulated digestion experiment revealed that SA/PCA/Fe hydrogel could control the release of anthocyanins in the simulated gastrointestinal tract. To sum up, this present study might provide a safer and feasible way for the delivery of bioactive substances.

3D printed swelling-driven shape-morphing pH-responsive hydrogel gripper.

Stimuli-responsive soft robots have provided new directions for obtaining advanced biomedical healthcare systems, such as targeted drug delivery capsules, less-invasive biopsy tools, and untethered microsurgical robots. We designed, 3D printed, and tested diverse time-dependent shape changeable 3D pH-responsive soft grippers consisting of N-isopropylacrylamide (NIPAM) and N-isopropylacrylamide-co-acrylic acid (NIPAM-AAc) bilayer. We found that the swelling/deswelling-driven actuation of the pH-responsive NIPAM/NIPAM-AAc gripper is primarily affected by the volume percent (% v/v) of the acrylic acid (AAc) and intensity of UV light. We expect that this study can be applied to untethered pH-responsive soft grippers as smart drug delivery capsules or biopsy tools in biomedical healthcare systems.

PH and temperature dual-responsive hydrogel actuator with bidirectional bending behavior and ultra large bending angle

Smart hydrogels have received attentions for the great potentials in biomedical and robots applications. However, the deformation performance of hydrogels still needs to be improved, especially for the pH and thermal dual responsive hydrogels. In this study, a pH and temperature dual-responsive poly(acrylamide-acrylic acid-3-acrylamidophenylboronic acid)/Poly(N-isopropylacrylamide) (P(AAm-AAc-3-AAPBA)/PNIPAM) bilayer structures have been prepared by UV polymerization. The PNIPAM layer shrinks/swells when the temperature is higher/lower than the low critical solution temperature, while P(AAm-AAc-3-AAPBA) layer will swell/shrink when pH is too high/low. The volume change trend of the two layer is different, resulting in the bending behaviors of P(AAm-AAc-3-AAPBA)/PNIPAM hydrogel actuator. The bidirectional bending performance can be reversibly, repeatedly, and precisely controlled by pH and temperature-induced cooperative swelling-shrinking properties from both layers. The bending angle of the bilayer structure achieves about 1420° at the environment of pH 2 and 55 ℃. It takes about 70 s to convert the bending angle of the bilayer structures from 355° (10 ℃, pH 2) to −360° (55 ℃, pH 12). In addition, three kinds of biomimetic hydrogel structures, such as mechanical gripper, bionic flower and bionic hand, have been prepared and demonstrated good performance. The obtained P(AAm-AAc-3-AAPBA)/PNIPAM hydrogels exhibit excellent pH and thermal responsive bending properties, which enable them as an ideal smart hydrogel system.

Injectable multifunctional carboxymethyl chitosan/hyaluronic acid hydrogel for drug delivery systems

Injectable hydrogels with notable mechanical properties and self-healing ability are promising carriers for use as a drug delivery system. Here, adipic acid dihydrazide (ADH) and calcium ions (Ca2+) were introduced into quaternary ammonium carboxymethyl chitosan and aldehyde-modified hyaluronic acid hydrogels (QCS + OHA). The hydrogels were synthesized through the interaction of the Schiff bases (imine bonds, acylhydrazone bonds) and coordination bonds via a facile one-step approach. The gelation time (∼54 s) ensured excellent injectability. The QCS + OHA + ADH + Ca2+ hydrogel had notable mechanical properties (compressive stress up to 896.30 KPa), good self-healing ability (up to 94 %), good pH responsiveness, and excellent antibacterial properties. In addition, the QCS + OHA + ADH + Ca2+ hydrogel had a high drug loading capacity (121.3 mg/g) and sustained drug release behaviour (≥120 h). The results of cytotoxicity tests showed a high cell proliferation rate (up to 98 %) and good cytocompatibility. In summary, this work presents an injectable and self-healing pH-responsive hydrogel that can be used as a carrier for drug delivery systems.

PH-Sensitive Hydrogel Bilayers: Investigation on Transient Swelling-Induced Bending through Analytical and FEM Approaches.

pH-responsive hydrogels are recognized as versatile sensors and actuators due to their unique time-dependent properties. Specifically, pH-sensitive hydrogel-based bilayers exhibit remarkable bending capabilities when exposed to pH-triggered swelling. This study introduces a semi-analytical technique that combines non-linear solid mechanics with ionic species transport to investigate the bending behavior of such bilayers. The technique is validated through numerical simulations, exploring the influence of kinetic and geometric properties on bilayer behavior. The results highlight the significance of the interfacial region, particularly in configurations with lower hydrogel geometric ratios, which are susceptible to rupture. The study also uncovers the benefits of a lower hydrogel layer ratio in improving the swelling rate and final deflection, with a stronger effect observed in the presence of a buffer solution. Additionally, the compressibility of the elastomer contributes to the durability of the final bent shape. These findings enhance our understanding of pH-sensitive hydrogel-based bilayers and offer valuable insights for their design and optimization in diverse applications.

PH-Responsive Gallol-Functionalized Hyaluronic Acid-Based Tissue Adhesive Hydrogels for Injection and Three-Dimensional Bioprinting.

The major challenges of hyaluronic acid-based bioinks in extrusion-based three-dimensional bioprinting are poor printability and low printing accuracy. To tackle the challenges, we developed a bioink in which two components are blended: gallic acid-functionalized hyaluronic acid (HAGA) and hyaluronic acid methacrylate (HAMA). In the precursor phase, the blend's HAGA component enables pH-dependent viscosity modulation that results in improved injectability and printability at physiological temperature. Postprinting, the blend's HAMA component is photocrosslinked to create a true hydrogel with a complementary network of both HAGA and HAMA. The ready structures of the HAGA-HAMA hydrogel showed sufficient printing quality and accuracy compared to plain HAMA. The blend also displayed enhanced viscoelastic properties and stable swelling behavior. In addition to the pH tunability, the HAGA component also imparted tissue adhesion and antioxidant activity. This bioink has the potential to be printed directly on an infected wound site due to its adhesiveness to tissue and dimensional stability in situ.

Bioinspired pH-Responsive Microalgal Hydrogels for Oral Insulin Delivery with Both Hypoglycemic and Insulin Sensitizing Effects.

The oral form of insulin is more convenient and has better patient compliance than subcutaneous or intravenous insulin. Current oral insulin preparations, however, cannot overcome the enzyme barrier, chemical barrier, and epithelial barrier of the gastrointestinal tract completely. In this study, a microalgae-based oral insulin delivery strategy (CV@INS@ALG) was developed using Chlorella vulgaris (CV)-based insulin delivery system cross-linking with sodium alginate (ALG). CV@INS@ALG could overcome the gastrointestinal barrier, protect insulin from harsh gastric conditions, and achieve a pH-responsive drug release in the intestine. CV@INS@ALG might contribute to two mechanisms of insulin absorption, including direct insulin release from the delivery system and endocytosis by M cells and macrophages. In the streptozotocin (STZ)-induced type 1 diabetic mouse model, CV@INS@ALG showed a more effective and long-lasting hypoglycemic effect than direct insulin injection and did not cause any damage to the intestinal tract. Additionally, the long-term oral administration of the carrier CV@ALG effectively ameliorated gut microbiota disorder, and significantly increased the abundance of probiotic Akkermansia in db/db type 2 diabetic mice, thereby enhancing the insulin sensitivity of mice. Microalgal insulin delivery systems could be degraded and metabolized in the intestinal tract after oral administration, showing good biodegradability and biosafety. This insulin delivery strategy based on microalgal biomaterials provides a natural, efficient, and multifunctional solution for oral insulin delivery.

Preparation of pH-responsive magnetic nanocomposite hydrogels based on k-carrageenan/chitosan/silver nanoparticles: Antibacterial carrier for potential targeted anticancer drug delivery

This study reports the development of new pH-responsive drug delivery systems that are important for the treatment of cancer. The Mentha plant extract was obtained and then used for the biosynthesis of magnetic Ag bio nanoparticles (M-Ag bio-NPs). They were added in the formulation of hybrid hydrogel of k-carrageenan (k-Cr) and chitosan (CS) toward the synthesis of magnetic nanocomposite hydrogels. Their chemical structure and morphology were characterized by different analyses. Doxorubicin (DOX) was used as a model anticancer drug to study the targeted drug release behavior of the synthesized nanocomposite hydrogels (loading capacity: about 98 %). In vitro drug release studies showed that the release profile was noticeably controlled in a pH-dependent manner (higher drug release at pH 5). The antibacterial assessment confirmed the high antibacterial activity for the synthesized hydrogel against S. aureus (MIC values 39.06 μg/mL) and E. coli (MIC values > 19.53). In-vitro cytotoxicity results (MTT assay) demonstrated good biocompatibility (higher than 88 %) for the blank nanocomposite hydrogels, while DOX-loaded nanocomposite hydrogels showed high toxicity (about 22 % in the concentration of 20 μg/mL) against HeLa cells. The results showed that the present nanocomposite hydrogels can be suggested for potential application as an antibacterial and anticancer carrier.

Hydrogel-Encapsulated Biofilm Inhibitors Abrogate the Cariogenic Activity of Streptococcus mutans.

We designed and synthesized analogues of a previously identified biofilm inhibitor IIIC5 to improve solubility, retain inhibitory activities, and to facilitate encapsulation into pH-responsive hydrogel microparticles. The optimized lead compound HA5 showed improved solubility of 120.09 μg/mL, inhibited Streptococcus mutans biofilm with an IC50 value of 6.42 μM, and did not affect the growth of oral commensal species up to a 15-fold higher concentration. The cocrystal structure of HA5 with GtfB catalytic domain determined at 2.35 Å resolution revealed its active site interactions. The ability of HA5 to inhibit S. mutans Gtfs and to reduce glucan production has been demonstrated. The hydrogel-encapsulated biofilm inhibitor (HEBI), generated by encapsulating HA5 in hydrogel, selectively inhibited S. mutans biofilms like HA5. Treatment of S. mutans-infected rats with HA5 or HEBI resulted in a significant reduction in buccal, sulcal, and proximal dental caries compared to untreated, infected rats.

Colloidal curcumin-laden pH-responsive hydrogels: A promising approach to enhance solubility, dissolution, and permeation of hydrophobic drug

Colloidal curcumin-laden pH-responsive hydrogels: A promising approach to enhance solubility, dissolution, and permeation of hydrophobic drug

Green synthesis of nano silver-embedded carboxymethyl starch waste/poly vinyl alcohol hydrogel with photothermal sterilization and pH-responsive behavior

Bacterial wound infections remain a significant health issue of great concern. Hence, there is a need to develop a novel material with antibacterial properties and smart functions. In this study, the effects of silver nanoparticles content (AgNPs) on properties of photothermal and pH-responsive nanocomposite hydrogels were investigated. The nanocomposite hydrogel samples were prepared using cassava starch waste modified by carboxymethylation (CMS), and mixed with poly vinly alcohol (PVA) and tannic acid (TA). The presence of AgNPs in the hydrogel samples enhanced antibacterial activities and photothermal conversion ability. The use of as-prepared hydrogel using 200 mM silver nitrate (H-AgNPs-200) combined with near infrared (NIR) radiation produced 100 % antibacterial efficiency for Escherichia coli (E.coli) and 98.2 % for Staphylococcus aureus (S.aureus). Furthermore, the H-AgNPs-200 also provided the highest storage modulus at 8.78 kPa. The obtained nanocomposite hydrogel was shown to exhibit pH-responsive release of TA. Under NIR radiation, higher release of TA at different pH was observed. The cytotoxicity study indicated that the nanocomposite hydrogels had good biocompatibility. Hence, the development of nanocomposite hydrogel-based CMS from cassava starch waste/PVA/AgNPs is a promising and sustainable approach where agro-waste product is used as the base material for medical application in wound dressing.

Antibacterial and Cytocompatible pH-Responsive Peptide Hydrogel.

A short peptide, FHHF-11, was designed to change stiffness as a function of pH due to changing degree of protonation of histidines. As pH changes in the physiologically relevant range, G' was measured at 0 Pa (pH 6) and 50,000 Pa (pH 8). This peptide-based hydrogel is antimicrobial and cytocompatible with skin cells (fibroblasts). It was demonstrated that the incorporation of unnatural AzAla tryptophan analog residue improves the antimicrobial properties of the hydrogel. The material developed can have a practical application and be a paradigm shift in the approach to wound treatment, and it will improve healing outcomes for millions of patients each year.

Polyurethane Shape Memory Polymer/pH-Responsive Hydrogel Hybrid for Bi-Function Synergistic Actuations

Stimuli-responsive actuating hydrogels response to the external stimulus with complex deformation behaviors based on the programmable anisotropic structure design are one of the most important smart soft materials, which have great potential applications in artificial muscles, smart values, and mini-robots. However, the anisotropic structure of one actuating hydrogel can only be programmed one time, which can only provide single actuating performance, and subsequently, has severely limited their further applications. Herein, we have explored a novel SMP/hydrogel hybrid actuator through combining polyurethane shape memory polymer (PU SMP) layer and pH-responsive polyacrylic-acid (PAA) hydrogel layer by a napkin with UV-adhesive. Owing to both the super-hydrophilicity and super-lipophilicity of the cellulose-fiber based napkin, the SMP and the hydrogel can be bonded firmly by the UV-adhesive in the napkin. More importantly, this bilayer hybrid 2D sheet can be programmed by designing a different temporary shape in heat water which can be fixed easily in cool water to achieve various fixed shapes. This hybrid with a fixed temporary shape can achieve complex actuating performance based on the bi-functional synergy of temperature-triggered SMP and pH-responsive hydrogel. The relatively high modulus PU SMP achieved high to 87.19% and 88.92% shape-fixing ratio, respectively, correspond to bending and folding shapes. The hybrid actuator can actuate with the 25.71 °/min actuating speed. Most importantly, one SMP/hydrogel bi-layer hybrid sheet was repeatedly programmed at least nine times in our research to fix various temporary 1D, 2D and 3D shapes, including bending, folding and spiraling shapes. As a result, only one SMP/hydrogel hybrid can provide various complex stimuli-responsive actuations, including the reversable bending-straightening, spiraling-unspiraling. A few of the intelligent devices have been designed to simulate the movement of the natural organisms, such as bio-mimetic "paw", "pangolin" and "octopus". This work has developed a new SMP/hydrogel hybrid with excellent multi-repeatable (≥9 times) programmability for high-level complex actuations, including the 1D to 2D bending and the 2D to 3D spiraling actuations, which also provides a new strategy to design other new soft intelligent materials and systems.

PH-responsive chitosan/acrylamide/gold/nanocomposite supported with silver nanoparticles for controlled release of anticancer drug

In this study, we prepared a pH-responsive nanocomposite hydrogel based on chitosan grafted with acrylamide monomer and gold nanoparticles using gamma irradiation method (Cs-g-PAAm/AuNPs). The nanocomposite was enhanced with a layer coating of silver nanoparticles to improve the controlled release of the anticancer drug fluorouracil while increasing antimicrobial activity and decreasing the cytotoxicity of silver nanoparticles in nanocomposite hydrogel by combining with gold nanoparticles to enhance the ability to kill a high number of liver cancer cells. The structure of the nanocomposite materials was studied using FTIR spectroscopy and XRD patterns, which demonstrated the entrapment of gold and silver nanoparticles within the prepared polymer matrix. Dynamic light scattering data revealed the presence of gold and silver in the nanoscale with the polydispersity indexes in the mid-range values, indicating that distribution systems work best. Swelling experiments at various pH levels revealed that the prepared Cs-g-PAAm/Au–Ag-NPs nanocomposite hydrogels were highly responsive to pH changes. Bimetallic pH-responsive Cs-g-PAAm/Au–Ag-NPs nanocomposites exhibit strong antimicrobial activity. The presence of AuNPs reduced the cytotoxicity of AgNPs while increasing their ability to kill a high number of liver cancer cells.Cs-g-PAAm/Au–Ag-NPs has a high amount of fluorouracil drug loaded at pH 7.4 reaching 95 mg/g with a maximum drug release of 97% within 300 min. Cs-g-PAAm/Au–Ag-NPs have been recommended to use as oral delivery of anticancer drugs because they secure the encapsulated drug in the acidic medium of the stomach and release it in the intestinal pH.

Swarming self-adhesive microgels enabled aneurysm on-demand embolization in physiological blood flow

The recent rise of swarming microrobotics offers great promise in the revolution of minimally invasive embolization procedure for treating aneurysm. However, targeted embolization treatment of aneurysm using microrobots has significant challenges in the delivery capability and filling controllability. Here, we develop an interventional catheterization-integrated swarming microrobotic platform for aneurysm on-demand embolization in physiological blood flow. A pH-responsive self-healing hydrogel doped with magnetic and imaging agents is developed as the embolic microgels, which enables long-term self-adhesion under biological condition in a controllable manner. The embolization strategy is initiated by catheter-assisted deployment of swarming microgels, followed by the application of external magnetic field for targeted aggregation of microrobots into aneurysm sac under the real-time guidance of ultrasound and fluoroscopy imaging. Mild acidic stimulus is applied to trigger the welding of microgels with satisfactory bio-/hemocompatibility and physical stability and realize complete embolization. Our work presents a promising connection between the design and control of microrobotic swarms toward practical applications in dynamic environments.

Redox- and pH-responsive alginate-based magnetic hydrogel: “Smart” drug delivery and protein corona studies

A redox- and pH-responsive magnetic hydrogel was designed and developed based on alginate (Alg) through double crosslinking approach for sustained and targeted delivery of doxorubicin (Dox). For this objective, Fe3O4 nanoparticles (NPs) were synthesized by a chemical co-precipitation method, and then their surfaces were modified using an amine-end capped silane coupling agent. Alginate was oxidized using sodium periodate. Then, an alginate-based pH- and redox-responsive magnetic hydrogel with and without Dox loading was synthesized by adding amine-modified Fe3O4 NPs and cystamine (Cys) moiety through “Schiff-Base” condensation followed by double crosslinking with CaCl2. Drug loading and encapsulation efficiencies were quantified as 3.4 ± 0.27 and 83 ± 2.7%, respectively. Drug release study by dialysis method approved pH- and redox-dependent drug release behavior. Interactions between hydrogel and human serum albumin (HSA) was investigated using spectroscopy techniques, and it was found that the developed hydrogel can interact strongly with HSA. The thermodynamic parameters of the protein-hydrogel interaction were also calculated, and it was revealed that interaction process is spontaneous and endothermic. The anti-cancer activity of the developed magnetic DDS was assessed against MCF7 cells by MTT assay. It was found that free Dox had a stronger cytotoxic effect in the first 24 and 48 h in comparison with Dox-loaded DDS, while after 72 h, the DDS showed higher anti-cancer activity, possibly due to the controlled release of drug by the hydrogel over time.