Preparation of bacterial cellulose/acrylic acid-based pH-responsive smart dressings by graft copolymerization method.

Conventional wound dressings used in trauma treatment have a single function and insufficient adaptability to the wound environment, making it difficult to meet the complex demands of the healing process. Stimuli-responsive hydrogels can respond specifically to the particular environment of the wound area and realize on-demand responsive release by loading active substances, which can effectively promote wound healing. In this paper, BC/PAA-pH responsive hydrogels (BPPRHs) were prepared by graft copolymerization of acrylic acid (AA) to the end of the molecular chain of bacterial cellulose (BC) network structure. Antibacterial pH-responsive 'smart' dressings were prepared by loading curcumin (Cur) onto the hydrogels. Surface morphology, chemical groups, crystallinity, rheological, and mechanical properties of BPPRHs were analyzed by different characterization methods. The drug release behavior under different physiological conditions and bacteriostatic properties of BPPRH-Cur dressings were also investigated. The results of structural characterization and performance studies show that the hydrogel has a three-dimensional mesh structure and can respond to wound pH in a 'smart' drug release capacity. The drug release behavior of the BPPRH-Cur dressings under different environmental conditions conformed to the logistic and Weibull kinetic models. BPPRH-Cur displayed good antimicrobial activity against common pathogens of wound infections such as E. coli, S. aureus, and P. aeruginosa by destroying the cell membrane and lysing the bacterial cells. This study lays the foundation for the development of new pharmaceutical dressings with positive health, economic and social benefits.

Fabrication, optimization, and in vitro validation of penicillin-loaded hydrogels for controlled drug delivery.

Bacterial infections present a major global challenge. Penicillin, a widely used antibiotic known for its effectiveness and safety, is frequently prescribed. However, its short half-life necessitates multiple high-dose daily administrations, leading to severe side-effects. Therefore, this study aims to address these issues by developing hydrogels which control the release of penicillin and alleviate its adverse effects. Various combinations of aspartic acid and acrylamide were crosslinked by N', N'-methylene bisacrylamide through a free radical polymerization process to prepare aspartic acid/acrylamide (Asp/Am) hydrogels. The fabricated hydrogels underwent comprehensive characterization to assess physical properties and thermal stability. The soluble and insoluble fractions and porosity of the synthesized matrix were evaluated by sol-gel and porosity studies. Gel fraction was estimated at 88-96%, whereas sol fraction was found 12-4% and porosity found within the 63-78% range for fabricated hydrogel formulations. Maximum swelling and drug release were seen at pH 7.4, demonstrating a controlled drug release from hydrogel networks. The results showed that swelling, porosity, gel fraction, and drug release increased with higher concentrations of aspartic acid and acrylamide. However, integration of N', N'-methylene bisacrylamide exhibited the opposite effect on swelling and porosity, while increasing gel fraction. All formulations followed the Korsymer-Peppas model of kinetics with 'r' values within the range of 0.9740-0.9980. Furthermore, the cytotoxicity study indicated an effective and safe use of hydrogel because the cell viability was higher than 70%. Therefore, these prepared hydrogels show promise candidates for controlled release of Penicillin and are anticipated to be valuable in clinical applications.

Synthesis of Gelatin Methacryloyl Analogs and Their Use in the Fabrication of pH-Responsive Microspheres.

pH-responsive hydrogels have numerous applications in tissue engineering, drug delivery systems, and diagnostics. Gelatin methacryloyl (GelMA) is a biocompatible, semi-synthetic polymer prepared from gelatin. When combined with aqueous solvents, GelMA forms hydrogels that have extensive applications in biomedical engineering. GelMA can be produced with different degrees of methacryloyl substitution; however, the synthesis of this polymer has not been tuned towards producing selectively modified materials for single-component pH-responsive hydrogels. In this work, we have explored two different synthetic routes targeting different gelatin functional groups (amine, hydroxyl, and/or carboxyl) to produce two GelMA analogs: gelatin A methacryloyl glycerylester (polymer A) and gelatin B methacrylamide (polymer B). Polymers A and B were used to fabricate pH-responsive hydrogel microspheres in a flow-focusing microfluidic device. At neutral pH, polymer A and B microspheres displayed an average diameter of ~40 µm. At pH 6, microspheres from polymer A showed a swelling ratio of 159.1 ± 11.5%, while at pH 10, a 288.6 ± 11.6% swelling ratio was recorded for polymer B particles.

pH factors in chronic wound and pH-responsive polysaccharide-based hydrogel dressings.

Chronic wounds present a significant healthcare challenge marked by complexities such as persistent bleeding, inhibited cell proliferation, dysregulated inflammation, vulnerability to infection, and compromised tissue remodeling. Conventional wound dressings often prove inadequate in addressing the intricate requirements of chronic wound healing, leading to slow healing and heightened susceptibility to infections in patients with prolonged medical conditions. Bacterial biofilms in chronic wounds pose an additional challenge due to drug resistance. Advanced wound dressings have emerged as promising tools in expediting the healing process. Among these, pH-responsive polysaccharide-based hydrogels exhibit immense prospect by adapting their functions to dynamic wound conditions. Despite their potential, the current literature lacks a thorough review of these wound dressings. This review bridges this gap by meticulously examining factors related to chronic wounds, current strategies for healing, and the mechanisms and potential applications of pH-responsive hydrogel wound dressings as an emerging therapeutic solution. Special focus is given to their remarkable antibacterial properties and significant self-healing abilities. It further explores the pH-monitoring functions of these dressings, elucidating the associated pH indicators. This synthesis of knowledge aims to guide future research and development in the field of pH-responsive wound dressings, providing valuable insights into their potential applications in wound care.

pH-Responsive injectable self-healing hydrogels loading Au nanoparticles-decorated bimetallic organic frameworks for synergistic sonodynamic-chemodynamic-starvation-chemo therapy of cancer.

A novel and efficient cancer therapy was developed using a smart hydrogel containing multifunctional bimetallic organic frameworks and anticancer drugs. The injectable self-healing hydrogel with pH-responsiveness was constructed through borate ester and imine bonds among dopamine-grafted sodium alginate (SADA), hydroxypropyl chitosan (HPCS) and 2-formylphenylboronic acid (2-FPBA). The Au nanoparticles-decorated Ti/Fe bimetallic organic framework tetragonal nanosheets (Au/TF-MOF TNS) were synthesized and incorporated into the hydrogel with the anticancer drugs doxorubicin (DOX). Upon intratumoral injection of nanocomposite hydrogel, the acidic tumor microenvironment triggered the cleavage of borate ester and imine bonds, causing the hydrogel to break down and accelerating the release of both Au/TF-MOF TNS and DOX. These Au/TF-MOF TNS functioned as nanozymes, producing hydroxyl radicals (·OH) for chemodynamic therapy (CDT), generating oxygen (O2) to support sonodynamic therapy (SDT), and depleting glucose for starvation therapy (ST). Additionally, the Au/TF-MOF TNS served as sonosensitizers, capable of converting O2 into singlet oxygen (1O2) upon ultrasound irradiation to achieve SDT. Therefore, this nanocomposite hydrogel system enabled synergistic sonodynamic-chemodynamic-starvation-chemo therapy (SDT-CDT-ST-CT) of cancer, presenting a promising platform for advanced cancer therapy strategies.

4D Multimaterial Printing of Soft Actuators with Spatial and Temporal Control.

Soft actuators (SAs) are devices which can interact with delicate objects in a manner not achievable with traditional robotics. While it is possible to design a SA whose actuation is triggered via an external stimulus, the use of a single stimulus creates challenges in the spatial and temporal control of the actuation. Herein, a 4D printed multimaterial soft actuator design (MMSA) whose actuation is only initiated by a combination of triggers (i.e., pH and temperature) is presented. Using 3D printing, a multilayered soft actuator with a hydrophilic pH-sensitive layer, and a hydrophobic magnetic and temperature-responsive shape-memory polymer layer, is designed. The hydrogel responds to environmental pH conditions by swelling or shrinking, while the shape-memory polymer can resist the shape deformation of the hydrogel until triggered by temperature or light. The combination of these stimuli-responsive layers allows for a high level of spatiotemporal control of the actuation. The utility of the 4D MMSA is demonstrated via a series of cargo capture and release experiments, validating its ability to demonstrate active spatiotemporal control. The MMSA concept provides a promising research direction to develop multifunctional soft devices with potential applications in biomedical engineering and environmental engineering.

Fabrication of resveratrol-loaded soy protein isolate-glycyrrhizin nanocomplex for improving bioavailability via pH-responsive hydrogel properties.

Resveratrol (RES) is a functional polyphenol that suffers from low water solubility and poor bioavailability. A novel RES-loaded soy protein isolate-dipotassium glycyrrhizinate (SPI-DG) nanocomplex (RES@SPI-DG) was designed and evaluated in this study. RES@SPI-DG was prepared using a simple but novel self-assembly ultrasonic-assisted pH-driven method. The interactions between RES and SPI-DG were non-covalent bonds, including hydrophobic interactions, hydrogen bonds, and van der Waals interactions. RES@SPI-DG exhibited high encapsulation efficiency (97.60 ± 0.38 %) and loading capacity (8.74 ± 0.03 %) of RES with a uniform small size (68.39 ± 1.10 nm). RES in RES@SPI-DG was in an amorphous state and demonstrated a 24-h apparent solubility 482.53-fold higher than bare RES. RES@SPI-DG also showed strong in vitro antioxidant properties. The pH-responsive hydrogel character of SPI-DG makes it an effective intestine-targeted delivery system that could retard the release of RES in a simulated stomach and accelerate it in a simulated intestine. In animal experiments, the bioavailability of RES@SPI-DG was 5.17 times higher than that of bare RES, and the biodistribution was also significantly improved. RES@SPI-DG demonstrated a strong hepatoprotective effect against overdose acetaminophen-induced liver injury. The SPI-DG complex might be a promising nano-platform for enhancing the bioavailability and efficacy of hydrophobic polyphenols such as RES.

Synthesis and Characterization of Novel pH-Responsive Aminated Alginate Derivatives Hydrogels for Tissue Engineering and Drug Delivery.

AIMS: The aims of this study are to synthesize new derivatives of sodium alginate that improve the inherent properties, such as hydrogel strengthening, and create environmental sensitivity, such as pH sensitivity, for use in drug delivery. BACKGROUND: Today, hydrogels, due to outstanding properties such as biodegradability, biocompatibility, mechanical properties, and response to stimuli properties, are widely used as harmless biomaterials in various fields in drug delivery, wound dressing, and tissue engineering. Stimulus-sensitive polymers significantly respond to slight changes in their environment. Different types of stimuli are used to influence the properties of polymers, the most important of which are temperature and pH because these are two vital factors in the human body; hence, temperature-sensitive and pHsensitive hydrogels have been extensively studied. The ability to absorb water and swell the hydrogel is due to hydrophilic chains in the hydrogel network, and water absorption by hydrogel can be controlled by response to the stimuli. Since hydrogels mimic human tissue, the ability to retain water in them is essential. As a result, it is considered in many biomedical drug delivery systems. Stimulusresponsive swelling can control diffusion out of and into the hydrogel network, which allows temporal and spatial control of drug release. When a drug is loaded onto a biodegradable and stimulisensitive hydrogel, the drug delivery system has the added advantage of sustained release of the drug, which reduces side effects. METHODS: In this study, two different hydrocarbons, [1,3-diaminopropane (DAP)] as a short-chain hydrocarbon, and [1,7-diaminoheptane (DAH)] as a long-chain hydrocarbon were grafted onto three types ofsodium alginate (SA), through amide bond linkages. The hydrogel copolymer matrices were compared with sodium alginate (SA) beads. The graft copolymers were characterized using FTIR, 1HNMR, XRD spectroscopy, elemental analysis (CHNS) and thermal analysis (TGA, DTA and DSC). An environmental scanning electron microscope (ESEM) was used to investigate the surface morphology of hydrogels. RESULTS: Effects of variables such as the length of hydrocarbon chains cross-linked to alginate, temperature, pH, and cross-linkers on the properties of hydrogels investigated in the temperature range of 2-70 ˚C and two different pH values (4.4 and 7.4). The results showed that when the hydrocarbon chain length of diamines decreases, the extent of cross-linking and strength of the hydrogels are increased. Other results suggest that the hydrogels obtained from high-viscosity alginate derivatives had positive pH sensitivity. Hydrogels prepared in this study demonstrated good mechanical and swelling ratios that are necessary for wound dressing. CONCLUSION: DAP-g-SA and DAH-g-SA pH-sensitive hydrogels were successfully synthesized through amide bond linkages. The new synthesis derivatives showed lower swelling levels at low pH (4.4). In contrast, their swelling levels at higher pH (7.4) were significantly enhanced. Higher swelling degree could be obtained at high pH. pH-responsive hydrogels are especially useful for various biological applications due to their unique feature of controlled swelling, biodegradability, biocompatibility, and fluid retention in their network structures. pH-responsive hydrogels, as intelligent systems, can be used in controlled-release drug delivery systems such as insulin delivery.

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.

Ultrafast Laser-Ablated Bioinspired Hydrogel-Based Porous Gating System for Sustained Drug Release.

Gating systems have been extensively researched in energy harvesting, lab-on-chip applications, and so forth. However, the controlled drug delivery system with artificial hydrogel-based porous gating systems (HPGSs) is rarely reported. Herein, a biomimetic HPGS with a pH-responsive hydrogel as the valve and polydimethylsiloxane as the frame is fabricated by in situ femtosecond laser microdrilling and subsequent ultraviolet exposure. The proposed HPGS loaded with doxorubicin hydrochloride (DOX) is stable under physiological conditions, has a low drug leakage rate, and can achieve sustained drug release in a low pH environment. The experimental results show that the drug release is mainly controlled by non-Fickian diffusion, which renders the dynamic speed control of molecular transport possible. Moreover, the HPGS can also be prepared into an antitumor microcapsule. The results of in vitro cell experiments demonstrate that DOX@HPGS can release drugs and achieve terrific therapeutic efficacy in the elimination of HeLa cells in the acidic environments around tumor cells. This functional HPGS is envisioned to be an ideal pH-response carrier for sustained drug release treatment of digestive diseases such as inflammatory bowel disease and gastrointestinal cancer.

Preparation of pH-Responsive Poly(γ-glutamic acid) Hydrogels by Enzymatic Cross-Linking.

pH-responsive hydrogels are important for oral drug release applications, and they are increasingly demanded to reduce the adverse side effects of drug release and improve drug absorption. In this study, a new type of pH-responsive hydrogel comprised of poly(γ-glutamic acid) modified with tyramine (PGA-Tyr) was developed through enzymatic cross-linking in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). The gelation rate, stiffness, swelling behavior, and pore size of the resulting hydrogels were tuned by changing the concentrations of HRP and H2O2 or the degree of substitution (DS) of PGA-Tyr. The pH responsiveness of the hydrogels was evaluated by the swelling ratio in solutions with various pH values, and their pH responsiveness exhibited a good reversibility in pH 2.0 and 7.0 solutions. The degradation rate of the hydrogels in simulated intestinal fluid (SIF) was faster than that in simulated gastric fluid (SGF). Moreover, indomethacin (IM), a hydrophobic drug model, was encapsulated in the hydrogels by rapid in situ gelation, and the pH-dependent drug release of IM-loaded hydrogels was achieved in SGF and SIF. Importantly, when IM was entrapped in pluronic F-127 to form drug micelles, the burst release of the IM-micelle-loaded hydrogels with a high DS of PGA-Tyr was remarkably decreased in SGF, and sustained drug release was presented in SIF. Thus, pH-responsive PGA-based hydrogels have tremendous promise for biomedical applications, especially oral drug delivery.

Fenugreek seed mucilage grafted poly methacrylate pH-responsive hydrogel: A promising tool to enhance the oral bioavailability of methotrexate.

This study aimed to develop the Fenugreek seed mucilage-based pH-responsive hydrogel system in order to improve the oral bioavailability of methotrexate (MTX). Fenugreek seed mucilage (FSM) was extracted from Trigonella foenum-graecum seeds. F1-F9 formulations of pH-responsive hydrogels were prepared using various FSM ratios, methacrylic acid (MAA), and methylene bis acrylamide (MBA) via free radical polymerization technique. Swelling behavior and in vitro drug release studies of prepared hydrogels were evaluated. Toxicity studies of prepared hydrogels were performed on normal cells and on Wistar rats (n = 6). Moreover, in vivo pharmacokinetics parameters were studied on albino rabbits. Hydrogels formation was confirmed by FTIR analysis, thermal analysis and SEM studies. The maximum swelling of hydrogel was found to be 384.7% at pH 7.4. MTX-loaded hydrogel showed the controlled release of MTX up to 24 h following Super Case II transport. Prepared hydrogels exhibited no toxicity in normal cells as well as in experimental subjects. MTX loaded hydrogels exhibited less inhibition compared to free MTX on Hela cells. In Vivo studies revealed 7.5-fold improved oral bioavailability of MTX with higher Cmax (928 ng/mL). These results indicate that the pH-responsive hydrogel system based on FSM is a promising tool for the controlled delivery of MTX.

Modified chitosan-hyaluronic acid based hydrogel for the pH-responsive Co-delivery of cisplatin and doxorubicin.

Combination chemotherapy has attracted more attention in the field of anticancer treatment due to the synergetic effects achieved in the targeted delivery of anticancer drugs. In the present work a hydrogel-based drug delivery system (CS-NSA/A-HA) was successfully developed from chitosan modified by nitrosalicylaldehyde and aldehyde hyaluronic acid. Anticancer drugs, Cisplatin (CDDP) and Doxorubicin (DOX) were incorporated into this hydrogel separately and a dual drug loaded system was synthesized and the potential of the single and dual drug loaded materials for lung cancer therapy was compared. The obtained hydrogel was characterized by various spectroscopic techniques. Morphological studies conducted by FE-SEM analysis. The loading and encapsulation efficiencies and percentage of drug release were determined by UV-Vis spectroscopy at different pHs. Cytotoxicity studies performed in A549 lung cancer cells confirmed the enhanced activity of the material as a dual drug carrier compared with the single loaded system. All the findings strongly suggest the applicability of the material for lung cancer therapy.

Novel Black Seed Polysaccharide Extract-g-Poly (Acrylate) pH-Responsive Hydrogel Nanocomposites for Safe Oral Insulin Delivery: Development, In Vitro, In Vivo and Toxicological Evaluation.

Oral delivery of insulin has always been a challenging task due to harsh gut environment involving variable pH and peptidase actions. Currently, no Food and Drug Administration (FDA) approved oral insulin formulation is commercially available, only intravenous (IV) or subcutaneous (SC) routes. Therefore, it is really cumbersome for diabetic patients to go through invasive approaches for insulin delivery on daily basis. In the present study, a novel pH-responsive hydrogel nanocomposite (NC) system was developed and optimized for safe oral delivery of insulin. Black seed polysaccharide extract-based hydrogel (BA hydrogel) was formulated by free radical polymerization and loaded with insulin. Blank BA hydrogel was also incorporated with insulin-loaded montmorillonite nanoclay (Ins-Mmt) to form an Ins-Mmt-BA hydrogel NC and compared with the insulin-loaded hydrogel. Swelling, sol-gel analysis and in vitro release studies proved that Ins-Mmt-BA6 hydrogel NC has the best formulation, with 96.17% maximum insulin released in 24 h. Kinetic modeling applied on insulin release data showed the Korsemeyer-Peppas model (R2 = 0.9637) as the best fit model with a super case II transport mechanism for insulin transport (n > 0.89). Energy Dispersive X-ray (EDX) Spectroscopy, Fourier Transformed Infrared (FTIR) spectroscopy and Powdered X-ray diffraction (PXRD) analysis results also confirmed successful development of a hydrogel NC with no significant denaturation of insulin. Toxicity results confirmed the safety profile and biocompatibility of the developed NC. In vivo studies showed a maximum decrease in blood glucose levels of 52.61% and percentage relative bioavailability (% RBA) of 26.3% for an Ins-Mmt-BA hydrogel NC as compared to BA hydrogels and insulin administered through the SC route.

Multifunctional Oxidized Succinoglycan/Poly(N-isopropylacrylamide-co-acrylamide) Hydrogels for Drug Delivery.

We prepared the self-healing and temperature/pH-responsive hydrogels using oxidized succinoglycan (OSG) and a poly (N-isopropyl acrylamide-co-acrylamide) [P(NIPAM-AM)] copolymer. OSG was synthesized by periodate oxidation of succinoglycan (SG) isolated directly from soil microorganisms, Sinorhizobium meliloti Rm1021. The OSG/P(NIPAM-AM) hydrogels were obtained by introducing OSG into P(NIPAM-AM) networks. The chemical structure and physical properties of these hydrogels were characterized by ATR-FTIR, XRD, TGA, and FE-SEM. The OSG/P(NIPAM-AM) hydrogels showed improved elasticity, increased thermal stability, new self-healing ability, and 4-fold enhanced tensile strength compared with the P(NIPAM-AM) hydrogels. Furthermore, the 5-FU-loaded OSG/P(NIPAM-AM) hydrogels exhibited effective temperature/pH-responsive drug release. Cytotoxicity experiments showed that the OSG/P(NIPAM-AM) hydrogels were non-toxic, suggesting that OSG/P(NIPAM-AM) hydrogels could have the potential for biomedical applications, such as stimuli-responsive drug delivery systems, wound healing, smart scaffolds, and tissue engineering.

Fabrication, Structure and Functional Characterizations of pH-Responsive Hydrogels Derived from Phytoglycogen.

The pH-responsive hydrogels were obtained through successive carboxymethylation and phosphorylase elongatation of phytoglycogen and their structure and functional characterizations were investigated. Phytoglycogen (PG) was first carboxymethylated to obtain carboxymethyl phytoglycogen (CM-PG) with degree of substitution (DS) at 0.15, 0.25, 0.30, and 0.40, respectively. Iodine staining and X-ray diffraction analysis suggested that the linear glucan chains were successfully phosphorylase-elongated from the non-reducing ends at the CM-PG surface and assembled into the double helical segments, leading to formation of the hydrogel. The DS of CM-PG significantly influenced elongation of glucan chains. Specifically, fewer glucan chains were elongated for CM-PG with higher DS and the final glucan chains were shorter, resulting in lower gelation rate of chain-elongated CM-PG and lower firmness of the corresponding hydrogels. Scanning electron microscope observed that the hydrogels exhibited a porous and interconnected morphology. The swelling ratio and volume of hydrogels was low at pH 3-5 and then became larger at pH 6-8 due to electrostatic repulsion resulting from deprotonated carboxymethyl groups. Particularly, the hydrogel prepared from chain-elongated CM-PG (DS = 0.25) showed the highest sensitivity to pH. These results suggested that phosphorylase-treated CM-PG formed the pH-responsive hydrogel and that the elongation degree and the properties of hydrogels depended on the carboxymethylation degree. Thus, it was inferred that these hydrogels was a potential carrier system of bioactive substances for their targeted releasing in small intestine.

Security-Enhanced 3D Data Encryption Using a Degradable pH-Responsive Hydrogel.

Based on degradable pH-responsive hydrogel, we report on an enhanced three-dimensional data encryption security technique in which a pH value is used for information manipulation. Featuring three types of states upon the pH value variation, namely, shrinkage, expansion and degradation, the hydrogel renders a limited pH value window as the "key" for information decryption. The pH-dependent shrinkage-to-expansion conversion of the hydrogel leads to a threshold pH value for retrieving the recorded data, whilst the degradability of the hydrogel, which can be tuned by adjusting the composition ratio of PEGDA/AAc, gives rise to a second threshold pH value for irreversibly sabotaging the retrieved data. Pre-doping silver ions in the hydrogel facilitates explicit recording and reading of binary data in forms of three-dimensional silver patterns through photoreduction and scattering, respectively, with a femtosecond laser. By accurately matching the vertical spacing of the encoded silver nanopatterns with the diffraction-limited focal depth of the decryption microscope, we can tune the pH value to encrypt and retrieve information recorded in layers and set a critical pH value to smash encoded information, which proves a highly secured 3D data encoding protocol. This strategy can effectively enrich data encryption techniques, vastly enhancing data security within unattained chemical dimensions.

Multifunctional alginate-based hydrogel with reversible crosslinking for controlled therapeutics delivery.

Glycan-based alginate hydrogels have great potential in creating new vehicles with responsive behavior and tunable properties for biomedicine. However, precise control and tunability in properties present major barrier for clinical translation of these materials. Here, we report the synthesis of pH responsive anthracene modified glycan-based hydrogels for selective release of therapeutic molecules. Hydrogels were crosslinked through simultaneous photopolymerization of vinyl groups and photodimerization of anthracene. Incorporation of anthracene into these gels leads to reversible control on crosslinking and transition between gel/sol states through dimerization/dedimerization of anthracene groups. Chemotherapeutic drug doxorubicin-loaded hydrogels were then tested in a cancer mimetic microenvironment where 85% of the drug was released from anthracene-conjugated hydrogels at pH 2 for 6 days. Control on gelation with anthracene incorporation was observed through alterations in modulus, where storage modulus was increased two-fold with anthracene conjugation during photopolymerization and photodimerization. Furthermore, cell survival analysis revealed that anthracene conjugation could selectively compromise cancer cell viability without inducing significant toxicity on healthy fibroblasts. This study combines light-induced control of crosslink density due to anthracene and pH-triggered therapeutics delivery with alginate. The approach would be applicable for systems where multiple control is required with high precision.

Dual pH-Responsive Hydrogel Actuator for Lipophilic Drug Delivery.

As one of the most promising drug delivery carriers, hydrogels have received considerable attention in recent years. Many previous efforts have focused on diffusion-controlled release, which allows hydrogels to load and release drugs in vitro and/or in vivo. However, it hardly applies to lipophilic drug delivery due to their poor compatibility with hydrogels. Herein, we propose a novel method for lipophilic drug release based on a dual pH-responsive hydrogel actuator. Specifically, the drug is encapsulated and can be released by a dual pH-controlled capsule switch. Inspired by the deformation mechanism of Drosera leaves, we fabricate the capsule switch with a double-layer structure that is made of two kinds of pH-responsive hydrogels. Two layers are covalently bonded together through silane coupling agents. They can bend collaboratively in a basic or acidic environment to achieve the "turn on" motion of the capsule switch. By incorporating an array of parallel elastomer stripes on one side of the hydrogel bilayer, various motions (e.g., bending, twisting, and rolling) of the hydrogel bilayer actuator were achieved. We conducted an in vitro lipophilic drug release test. The feasibility of this new drug release method is verified. We believe this dual pH-responsive actuator-controlled drug release method may shed light on the possibilities of various drug delivery systems.

pH responsive doxorubucin loaded zein nanoparticle crosslinked pectin hydrogel as effective site-specific anticancer substrates.

Herein, we report pH-responsive hydrogels of hierarchically self-assembled protein (zein, in the form of its nanoparticles of size 80-120 nm) and polysaccharide (pectin), where gelation occurred below pH 3 in the absence of crosslinkers, which we used for encapsulation and release of anticancer drug, Doxorubicin (DOX) in the cell nucleus. These nanoparticles, spherical in shape, in addition to helping in the formation of gel network also encapsulate the drug and pectin layer adsorbed on the surface of these nanoparticle allows for the drying, redispersion and enhanced swelling. A monovalent salt-dependent study performed in the concentration range of 1-100 mM clearly showed the associative interaction between the zein nanoparticles and pectin chains were hydrophobic in nature. FTIR results confirmed the loading of the drug inside the nanoparticles. Melting profile studies of these gels revealed that encapsulation of drug did not change the thermo-physical properties. Doxorubicin drug loaded hydrogels exhibited superior cytotoxicity towards cervical cancer cell lines by inducing intracellular-antioxidative stress-based apoptosis. Confocal microscopy revealed that the hydrogels required quite less time of 4 h to completely penetrate the cells assisted by the charge specific electrostatic interaction between the negatively charged HeLa cells and positively charged crosslinks. The data, further revealed that these pH specific hydrogels were suitable for release of the drug in cell nucleus is assisted by the acidic environment of cellular organelles, and hence have a potential in cancer therapy with minimal collateral damage to healthy cells.