Albumin Hydrogel Research Articles

Tissue-Adaptive BSA Hydrogel with Dual Release of PTX and bFGF Promotes Spinal Cord Injury Repair via Glial Scar Inhibition and Axon Regeneration.

Spinal cord injury (SCI) is a severe clinical disease usually accompanied by activated glial scar, neuronal axon rupture, and disabled motor function. To mimic the microenvironment of the SCI injury site, a hydrogel system with a comparable mechanical property to the spinal cord is desirable. Therefore, a novel elastic bovine serum albumin (BSA) hydrogel is fabricated with excellent adhesive, injectable, and biocompatible properties. The hydrogel is used to deliver paclitaxel (PTX) together with basic fibroblast growth factor (bFGF) to inhibit glial scar formation as well as promote axon regeneration and motor function for SCI repair. Due to the specific interaction of BSA with both drugs, bFGF, and PTX can be controllably released from the hydrogel system to achieve an effective concentration at the wound site during the SCI regeneration process. Moreover, benefiting from the combination of PTX and bFGF, this bFGF/PTX@BSA system significantly aided axon repair by promoting the elongation of axons across the glial scar with reduced reactive astrocyte secretion. In addition, remarkable anti-apoptosis of nerve cells is evident with the bFGF/PTX@BSA system. Subsequently, this multi-functionalized drug system significantly improved the motor function of the rats after SCI. These results reveal that bFGF/PTX@BSA is an ideal functionalized material for nerve repair in SCI.

Remodeling the tumor immune microenvironment through hydrogel encapsulated G-Rh2 in situ vaccine and systemic immunotherapy

Ginsenoside Rh2 (G-Rh2) is a vital bioactive compound in Traditional Chinese Medicine, celebrated for its strong pharmacological properties, particularly its potent antitumor effects. However, its poor water solubility and limited bioavailability have necessitated the development of a novel drug delivery method. In this study, we utilized an indocyanine green carboxylic acid-hydroxypropyl cellulose-abietic acid-bovine serum albumin hydrogel (ICG-HPC-AA/BSA hydrogel) as a tumor in situ vaccine to enhance the permeability, retention, and tumor-targeted therapeutic efficacy of G-Rh2. We examined the therapeutic impact of a G-Rh2-loaded hydrogel combined with systemic PD-1 antibody treatment in murine models of H22 liver cancer and CT26 colon cancer. Additionally, we explored the immune microenvironment of the tumors influenced by this in situ vaccination strategy.

Liposomal nano-encapsulation of bFGF combined with injectable BSA hydrogel for efficient burn wound healing

Rapid and scar-free healing of burn wounds is an urgent clinical issue. Basic fibroblast growth factor (bFGF) has been proven to promote the healing of burn wounds by accelerating ECM remodeling and angiogenesis. However, exudates from burn wounds can accelerate bFGF degradation, thereby affecting its bioactivity. This study proposes an effective protection strategy for bFGF that involves encapsulating bFGF in nanoliposomes (bFGF-NLip) and then incorporating bFGF-NLip into a bovine serum albumin (BSA) hydrogel. This hybrid hydrogel system (bFGF-NLip@B) could maintain the activity of bFGF, achieve sustained release, and allow phospholipids and cholesterol to penetrate the skin, thereby enabling bFGF to function in the dermis. The experimental results showed that the hydrogel was injectable with good mechanical properties and biocompatibility. In a mouse scald wound model, owing to the sustained release of bFGF and skin permeation function of the nanoliposomes, the hydrogel promoted granulation formation, collagen deposition, vascular regeneration, and re-epithelialisation, ultimately accelerating wound healing. In addition, the hydrogel effectively inhibited scar formation. This system provides novel insights into the delivery of bFGF and scar-free healing of burn wounds.

Antifouling and antimicrobial wearable electrochemical sweat sensors for accurate dopamine monitoring based on amyloid albumin composite hydrogels

Wearable electrochemical sweat sensors are potentially promising for health monitoring in a continuous and non-invasive mode with high sensitivity. However, due to the complexity of sweat composition and the growth of skin bacteria, the wearable sweat sensors may gradually lose their sensitivity or even fail over time. To deal with this issue, herein, we proposed a new strategy to construct wearable sweat sensors with antifouling and antimicrobial capabilities. Amyloid albumin hydrogels (ABSAG) were doped with two-dimensional (2D) nanomaterial MXene and CeO2 nanorods to obtain the antifouling and antimicrobial amyloid albumin composite hydrogels (ABSACG, CeO2/MXene/ABSAG), and the wearable sensors were prepared by modifying flexible screen-printed electrodes with the ABSACG. Within this sensing system, the hydrophilic ABSAG possesses strong hydration capability, and it can form a hydration layer on the electrode surface to resist biofouling in sweat. The 2D nanomaterial MXene dispersed in the hydrogel endows the hydrogel with good conductivity and electrocatalytic capability, while the doping of CeO2 nanorods further improves the electrocatalytic performance of the hydrogel and also provides excellent antimicrobial capability. The designed wearable electrochemical sensors based on the ABSACG demonstrated satisfying antifouling and antimicrobial abilities, and they were capable of detecting dopamine accurately in human sweat. It is expected that wearable sensors utilizing the antifouling and antimicrobial ABSACG may find practical applications in human body fluids analysis and health monitoring.

3D printed subcutaneous implant for prolonged delivery of tenofovir with desired release capability, biocompatibility, and viability

This study introduced a progressive approach to address the challenges associated with drug delivery in hepatitis B by developing a 3D printed subcutaneous implant. The implant, composed of a polymer-reinforced bovine serum albumin hydrogel crosslinked with glutaraldehyde, exhibited shear thinning and thixotropic behavior. This allows it to undergo transformation into an implant using a semisolid extrusion-based 3D printing technique. Thorough analysis encompassing physical, thermal, and spectroscopy assessments ensured thermal and chemical stability of the implant. Scanning electron microscopy revealed the highly porous microstructures of the hydrogel implant, enhancing its suitability for drug encapsulation. Swelling study showed only 7.88 % swelling of the implant after 28 days, suggesting restricted water movement into the implant matrix, leading to a gradual release of the encapsulated drug. The biodegradable nature of the implant was confirmed using an enzyme degradation study. Notably, the hydrogel implant exhibited sustained release of tenofovir of approximately 63 % over a 28-day period, presenting a promising avenue for prolonged therapeutic interventions in both hepatitis B. Furthermore, the crosslinked hydrogel was found to be cytocompatible in human kidney and dermal fibroblast cells. Overall, this work signifies a notable advancement in implantable drug delivery systems utilizing both hydrogel and the emerging 3D printing technique, offering a potential solution for sustained and localized treatment of chronic viral infections.

Microfluidics-derived hierarchical microparticles for the delivery of dienogest for localized endometriosis therapy

Drug therapy is one of the most important strategies for treating gynecological diseases. Local drug delivery is promising for achieving optimal regional drug exposure, considering the complex anatomy and dynamic environment of the upper genital tract. Here, we present microparticle-based microcarriers with a hierarchical structure for localized dienogest (DNG) delivery and endometriosis treatment. The microparticles were fabricated by microfluidics and consisted of photo-crosslinked bovine serum albumin hydrogel particles (D@P-B MPs) encapsulating DNG-loaded PLGA (poly lactic-co-glycolic acid) microspheres. Such design enables the microparticles to have sustained release capacity and cell adhesion ability. Based on this, the microparticles were applied for the treatment of peritoneal endometriosis through intraperitoneal injection. The performance of the microparticles in inhibiting the growth of ectopic lesions as well as their anti-inflammatory, anti-angiogenesis, and pelvic pain-relieving effects are well demonstrated in vivo. These findings indicate that the present hierarchical microparticles are good candidates for localized treatment of endometriosis and are promising for the management of gynecological diseases. STATEMENT OF SIGNIFICANCE: We prepared photo-crosslinked bovine serum albumin hydrogel particles (D@P-B MPs) encapsulating DNG-loaded PLGA microspheres using microfluidic electrospray. Such hierarchical structure provided multiple functions of the particles as drug carriers. The hierarchical microparticles not only supported the sustained release of drugs but also provided adhesion to human ectopic endometrial stromal cells. The hierarchical microparticles represented a localized treatment method for endometriosis and is promising for the management of gynecological diseases.

Serum albumin hydrogels designed by protein Re-association for self-powered intelligent interactive systems

Advancements in protein structural engineering have made it possible to design protein materials that can mediate between humans and intelligent systems, manifesting a combination of characteristics such as elastic recovery, electrical conductivity, and stability. This work describes the design of a hydrogel using bovine serum albumin (BSA), based on protein-protein interactions and sulfhydryl-alkene click reactions. The multiple α-helices of BSA were intertwined together by the multi-armed olefin derivatives, acting like Lego blocks to form a gel network and locking in bound water and ions, thus imparting mechanical recovery characteristics (demonstrating 80 % recovery after the compressive strain and 638 % after tensile strain), electrical conductivity, resistance to freezing (maintaining mechanical properties after being frozen at -20 °C for 48 h), biocompatibility (the cell viability of mouse pre-osteoblast-like cells in the hydrogels was 97.5 %), antimicrobial properties, and biodegradability to the BSA hydrogels. A multi-channel wireless signal acquisition system based on BSA hydrogel devices designed for bioenergy conversion and harvesting was developed for the real-time detection of human motion along with a human-mechanics interaction system for manipulating robotic gestures with simple human finger movements. This restructuring of the BSA structure represents a significant advancement in the systematic exploration of protein structures and the development of protein materials. These applications serve as a secure bridge between humans and energy storage devices.

Load-bearing columns inspired fabrication of ductile and mechanically enhanced BSA hydrogels

Currently, protein-based hydrogels are widely applied in soft materials, tissue engineering and implantable scaffolds owing to their excellent biocompatibility, and degradability. However, most protein-based hydrogels are soft brittle. In this study, a ductile and mechanically enhanced bovine serum albumin (BSA) hydrogel is fabricated by soaking the a 1-(3-dimethylaminopropyl)-3ethylcarbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) induced BSA hydrogel in (NH4)2SO4 solution. An EDC/NHS coupling reaction induce protein coupling reactions that cause the BSA skeleton to resemble architectural load-bearing walls, protecting the integrity of the hydrogel and preventing collapse. The effects of the BSA and (NH4)2SO4 concentrations on the hydrogel mechanics are evaluated, and the possible strengthening mechanism is discussed. Besides, the highly kosmotropic ions greatly enhance the hydrophobic interaction within BSA gels and dehydration effect and their mechanical properties were significantly enhanced. The various mechanical properties of hydrogels can be regulated over a large window by soaking hydrogels into various ions. And most of them can be washed away, maintaining high biocompatibility of the protein. Importantly, the protein hydrogels prepared by this strategy could also be modified as strain sensors. In a word, this work demonstrates a new, universal method to provide multi-functional, biocompatible, strength enhanced and regulable mechanical pure protein hydrogel, combining the Hofmeister effect with -NH2/-COOH association groups.

Albumin Hydrogel-Coated Mesoporous Silica Nanoparticle as a Carrier of Cationic Porphyrin and Ratiometric Fluorescence pH Sensor.

Here, we report that a mesoporous silica nanoparticle (MSN) coated with a fluoresceine-labeled bovine serum albumin (F-BSA) hydrogel layer works as a temperature-responsive nanocarrier for tetrakis-N-methylpyridyl porphyrin (TMPyP) and as a fluorescence ratiometric pH probe. F-BSA hydrogel-coated MSN containing TMPyP (F-BSA/MSN/TMPyP) was synthesized by thermal gelation of denatured F-BSA on the external surface of MSN. The F-BSA hydrogel layer was composed of an inner hard corona layer and an outer soft layer and was stable under physiological conditions. F-BSA/MSN/TMPyP exhibited temperature-dependent exponential release of TMPyP. In this release profile, the MSN was found to be a suitable host for stable encapsulation of tetracationic TMPyP by electrostatic interactions, and the F-BSA hydrogel layer mediated the diffusion of TMPyP from the MSN pore interior into the solution phase. Increasing temperature promoted partitioning of TMPyP from the pore interior to the F-BSA hydrogel layer, from where it was spontaneously released into the bulk solution phase by cation exchange. F-BSA/MSN/TMPyP also gave a linear ratiometric fluorescence response (1.3 per pH unit) in the pH range from 6.1 to 8.9.

Low fouling electrochemical sensing interfaces based on Bovine serum albumin hydrogel for the detection of protein biomarkers in human serum

The development of electrochemical biosensor capable of detecting specific biomarkers in real complex biological samples remains a challenge significantly relevant to a range of disease diagnostic applications. Herein an antifouling electrochemical biosensor suitable for biomarker detection in human serum was constructed based on protein hydrogels. A typical protein bovine serum albumin (BSA) was crosslinked with glutaraldehyde to form a hydrogel, which was freeze-dried and re-swollen to exhibit excellent antifouling capability. The rheological testing revealed that the prepared BSA hydrogel possessed good elasticity with a critical strain value of about 600 %, which is important for the construction of stable hydrogel-based biosensors. Following the immobilization of CA125 antibodies onto the BSA hydrogel modified electrode, an electrochemical biosensor for the detection of CA125 was constructed, with a linear range of 0.1 ∼ 1000 U mL−1 and a limit of detection of 0.026 U mL−1. Owing to the unique properties of the BSA hydrogel, the biosensor exhibited good stability and excellent antifouling performances, and it was able to detect CA125 in human serum with acceptable accuracy. The strategy of constructing low fouling biosensors based on hydrogels prepared from BSA with biocompatibility and widespread availability represented a very promising advance along the road to develop biosensing devices with robust operation in complex biological fluids.

Albumin hydrogels for repeated capture of drugs from the bloodstream and release into the tumor

Despite the efficacy of hydrogels for consistently delivering drugs to targeted areas (primarily tumors), these systems face challenges such as initial burst release, non-refillable drugs, and a lack of dosage control. To address these issues, a novel strategy has been developed to capture and release drugs from the bloodstream, thereby overcoming the limitations of traditional hydrogels. In this study, an innovative albumin hydrogel system was developed through a bioorthogonal reaction using azide-modified albumin and 4-arm PEG-DBCO. This system can repeatedly capture and release drugs over prolonged periods. Inspired by albumin-drug binding in vivo, this hydrogel can be injected intratumorally and acts as a reservoir for capturing drugs circulating in the bloodstream. Drugs captured in hydrogels are released slowly and effectively delivered to tumors through a “capture and release process.” Both the in vitro and in vivo results indicated that the hydrogel effectively captured and released drugs, such as indocyanine green and doxorubicin, over repeated cycles without compromising the activity of the drugs. Moreover, implanting the hydrogel at surgical sites successfully inhibited tumor recurrence through its drug capture-release capability. These findings establish the albumin hydrogel system as a promising capture-release platform that leverages drug-binding affinity to effectively deliver drugs to tumors, offering potential advancements in cancer treatment and post-surgery recurrence prevention.

Synthesis of hydrogels from fractionated proteins of Moringa oleifera Lam. seeds for the treatment of water contaminated with black reactive dye 5

AbstractAs has been portrayed in the literature, the main proteins extracted from the seeds of Moringa oleifera Lam. have coagulant and clarifying potential in water treatment. However, when using them as coagulant agents, sludge formation occurs, which is an environmental problem. Thus, it was proposed to synthesize hydrogels from the main Moringa seeds proteins and use them as adsorbents. This work aimed to synthesize albumin hydrogels and globulin hydrogels and evaluate their efficiency as adsorbents to remove the reactive black 5 dye. Through FTIR spectrum it was possible to confirm that the synthesis of hydrogels occurred successfully. The kinetic data fit the pseudo‐second order model for both hydrogels. The equilibrium isotherms showed that adsorption occurs in multilayers, due to Freundlich fitting. The maximum adsorption capacity occurred at 298 K and was 1.19 mg g−1 for the albumin hydrogel and 10.06 mg g−1 for the globulin hydrogel. Through the results it is possible to state that globulin hydrogel was more favourable for adsorption since it has a more porous morphology and requires less mass compared to albumin hydrogel.

Bovine Serum Albumin Hydrogel Formation: pH Dependence and Rheological Analyses.

In vitro evaluation of the physical properties of biopolymer-based hydrogels can help in understanding certain phenomena, such as liquid-liquid phase separation. The formation of bovine serum albumin (BSA) hydrogels was investigated in the pH range of 1.0 to 4.0. Hydrogels were formed in the pH range of 3.0 to 4.0, whereas viscous solutions were formed in the pH range of 1.5 to 2.5. Unexpectedly, formation of BSA hydrogel was observed in extremely acidic condition (pH 1.0). The circular dichroism spectra of BSA solutions were recorded at pH values of 1.0, 2.0, 3.0, and 7.0, and α-helix contents were determined from the ellipticity data at 222 nm. The α-helix content decreased with a decrease in pH, and this decrease was associated with the partial denaturation (F-isoform) and the denaturation (E-isoform) of BSA. However, the α-helix contents at pH 1.0 and 3.0 were similar. BSA hydrogels at pH 1.0 and 3.5 showed similar dynamic viscoelastic properties, further supporting the stereo structural change of BSA from the denatured E-isoform to the partially denatured F-isoform at pH 1.0. The study also focused on measuring viscoelasticity, a fundamental physical property of hydrogels, using traditional rheometer and with minimal sample volume. A highly reproducible procedure for measuring the viscoelastic properties of hydrogels was established using sample volumes of 200 and 350 μL.

Emerging albumin hydrogels as personalized biomaterials.

Developing biomaterials-based tissue engineering scaffolds with personalized features and intrinsic biocompatibility is appealing and urgent. Through utilizing various strategies, albumin, as the most abundant protein in plasma, could be fabricated into sustainable, cost-effective, and potentially personalized hydrogels that would display enormous biological applications. To date, much of the albumin-based research is primarily engrossed in using albumin as a therapeutic molecule or a drug carrier, not much as a scaffold for tissue engineering. For this reason, we have come up with a detailed and insightful review of recent progress in albumin-based hydrogels having an emphasis on production techniques, material characteristics, and biological uses. It is envisioned that albumin-based scaffolds would be appealing and useful platforms to meet current tissue engineering needs and achieve the goal of clinical translation to benefit patients. STATEMENT OF SIGNIFICANCE: The creation of autologous material-based scaffolds is a potential method for preventing immunological reactions and obtaining the best therapeutic results. Patient-derived albumin hydrogels may consequently provide improved opportunities for personalized treatment due to their abundant supply and minimal immunogenicity. To provide a detailed and insightful summary on albumin-based hydrogels, this review includes latest comprehensive information on their preparation procedures, features, and applications in 3D printing and other biomedical applications. The challenges, along with the future potential for implementing albumin-based hydrogels in clinics, have also been addressed.

Spectroscopic Characterization of the Binding and Release of Hydrophilic, Hydrophobic and Amphiphilic Molecules from Ovalbumin Supramolecular Hydrogels.

Protein-based hydrogels have attracted growing attention for pharmaceutical and biomedical applications. Ovalbumin (OVA), the hen egg white albumin, possessing good foaming and gelling properties and being widely used in the food industry, has recently been indicated as a potential pharmaceutical vehicle. In this study, the binding and release properties of pure OVA hydrogels were investigated by electron paramagnetic resonance (EPR) spin labeling. The comparative analysis between OVA and serum albumin (SA) hydrogels revealed the same release kinetics of hydrophilic 3-carbamoyl-proxyl and 3-carboxy-proxyl, suggesting the diffusion-dominated release of small probes from both hydrogel types. The results obtained with the amphiphilic 16-doxylstearate (16-DS) indicate that OVA, unlike SAs, does not possess a specific fatty acid binding site. However, the OVA hydrogels were able to accommodate a two-fold excess of 16-DS, resulting from protein thermally induced conformational changes, as confirmed by Raman spectroscopy. Similarly, the hydrophobic modified paullone ligand HL, which was initially free in the OVA solution, was bound in the hydrogel. The hydrogels were found to retain a significant amount of 16-DS and HL after 7-day dialysis in physiological saline. The observed facilitated binding of amphiphilic/hydrophobic molecules in OVA hydrogels compared to the solution, and their sustained release, demonstrate the applicability of OVA hydrogels in pharmaceutics.

Amyloid-Based Albumin Hydrogels.

Amyloid fibrils may serve as building blocks for the preparation of novel hydrogel materials from abundant, low-cost, and biocompatible polypeptides. This work presents the formation of physically cross-linked, self-healing hydrogels based on bovine serum albumin at room temperature through a straightforward disulfide reduction step induced by tris (2-carboxyethyl) phosphine hydrochloride. The structure and surface charge of the amyloid-like fibrils is determined by the pH of the solution during self-assembly, giving rise to hydrogels with distinct physicochemical properties. The hydrogel surface can be readily functionalized with the extracellular matrix protein fibronectin and supports cell adhesion, spreading, and long-term culture. This study offers a simple, versatile, and inexpensive method to prepare amyloid-based albumin hydrogels with potential applications in the biomedical field.

Integration of enzyme-encapsulated mesoporous silica between nanohole array electrode and hydrogel film for flow-type electrochemical biosensor.

We herein propose a simple and sensitive electrochemical flow biosensor platform without an external flow device. The sensing unit comprises a platinum nanohole array electrode deposited on a nanoporous track-etched membrane (PtNH/NPM), a packed-layer of glucose oxidase-encapsulated mesoporous silica particles (GOD/MPS), and bovine serum albumin hydrogel film (BSA gel film). This sensing unit was fixed at the open window at the side of the plastic container with internal solution containing NaCl as osmotic reagent. When the sample glucose solution (0.10mL) was pipetted at the sensing unit, a portion of the sample solution (5 μL) was spontaneously transferred into the BSA gel film. The concentration gradient of NaCl between the internal solution and the BSA gel film induced osmotic flow of water toward the internal solution. This osmotic flow assisted delivery of glucose to the GOD/MPS and enzymatically generated H2O2 to the PtNH/NPM. The proposed sensor could be used repeatedly and produced a linear current response for glucose, with a limit of detection of 16μM. These sensor performances confirmed availability of the sensor design utilizing the osmotic flow.

Bioresponsive cisplatin crosslinked albumin hydrogel served for efficient cancer combination therapy

Bioresponsive cisplatin crosslinked albumin hydrogel served for efficient cancer combination therapy

Denatured bovine serum albumin hydrogel-based electrochemical biosensors for detection of IgG.

Anantifouling sensing surface was constructed by crosslinking two-dimensional nanomaterial MXene with bovine serum albumin (BSA) denatured by urea previously. The immunoglobulin G (IgG) capture peptide was then modified to the surface to construct a highly selective antifouling electrochemical biosensor. Due to the large specific surface area and good electrical conductivity of MXene, the sensitivity of the biosensor is significantly enhanced. The biosensor at a working potential of around - 0.18V (vs. Ag/AgCl) provides a wide linear detection range (0.1 ng/mL to 10 µg/mL)for IgGwith alimit of detection of 23pg/mL (3σ/k). The result is consistent with that obtained from the commercial enzyme-linked immunosorbent kit. Compared with BSA, which is usually used as a passivator or blocker for biosensing platforms, the hydrogel formed through the peptide chain obtained from BSA with good hydrophilicity can provide a better antifouling sensing surface to resist nonspecific adsorption. The prepared biosensor can quantitatively detect the concentration of IgG in complex human serum with high sensitivity. Thus, the antifouling sensing surface constructed without expensive antifouling materials and complex process is expected to develop as a variety of electrochemical biosensors and used for the clinical testing of biomarkers. Graphical abstract An antifouling sensing surface was constructed by crosslinking two-dimensional nanomaterial MXene with bovine serum albumin (BSA) denatured by urea previously. The immunoglobulin G (IgG) capture peptide was then modified to the surface to construct a highly selective antifouling electrochemical biosensor.

Injectable redox albumin-based hydrogel with in-situ loaded dihydromyricetin

Albumin is widely used in clinics due to its demonstrated biological safety and functional flexibility. Hydrogels derived from natural albumin possess high moisture retention ability and good biodegradability, making albumin ideal biomaterials compared with synthetic polymers. Herein, by reducing disulfide bonds in bovine serum albumin molecules with glutathione and re-oxidizing the free thiols using dimethyl sulfoxide (DMSO) as additional oxidant, three-dimensional network was assembled, leading to the formation of hydrogel. Meanwhile, DMSO is also an excellent solvent for many drugs, and the hydrophobic drug dihydromyricetin (DMY) can be well dissolved in DMSO. During the crosslinking reaction, DMSO participated in fabricating a porous albumin hydrogel network. At the same time, increased loading of DMY and sustained release of DMY were achieved, improving bioavailability of hydrophobic drug DMY. Rheological test and cytotoxicity assay proved excellent elasticity and biocompatibility of the hydrogel. Self-healing property and narrow-needle injection provided potential application of the hydrogel as biomedical materials. This method for formation hydrogels and in situ loading of drugs may expand to preparing other drug loaded hydrogels and find wide applications.