Controlled Drug Delivery Research Articles

Atlas Drug-Eluting Coronary Stents Inhibit Neointimal Hyperplasia in Sheep Modeling.

Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity worldwide. Many patients with CAD require mechanical revascularization. However, restenosis after minimally invasive interventions is a major problem for these patients. Fortunately, the controlled drug delivery properties of drug-eluting stents seem to be able to overcome this problem. In this study, the pharmacodynamic and pharmacokinetic properties of Atlas Drug-eluting Coronary Stents coated with poly (lactic acid-coglycolic acid) (PLGA) were evaluated. This study included 20 non-atherosclerotic female sheep divided into 4 groups that included 4 study and 1 control animal randomly assigned to each group. Animals in the study groups were stented with Atlas Drug-eluting Coronary Stents, and the pharmacodynamic and pharmacokinetic properties were evaluated. Sirolimus was shown to have a statistically important effect on the vascular endothelium. With time, the decrease in sirolimus in blood samples was statistically significant. Two animals died after implantation; however no clinically significant side effects were observed in the others. The results in this study showed a significant reduction in neointimal hyperplasia after experimental implantation of Atlas Drug-eluting Coronary Stents coated with PLGA polymer. Pharmacokinetic studies also showed that the stent did not release a significant amount of sirolimus after 28 days.

HYDROPHILIC MATRIX TABLETS AS ORAL CONTROLLED DRUG DELIVERY SYSTEMS IN 20TH CENTURY: A REVIEW

Matrix systems are easy to formulate compared to other controlled release dosage forms. The manufacture of matrix tablets involves the direct compression of blend of drug, retardant material and additives to form a tablet in which drug is embedded in a matrix core of the retardant. Alternatively, retardant-drug blends may be granulated prior to compression. Of the three classes of retardant material used to formulate matrix tablets, polymers that form hydrophilic matrices are attracting the attention of pharmaceutical technologists. These polymers include Methyl cellulose (MC), Hydroxy ethyl cellulose (HEC), Hydroxy popyl methyl cellulose (HPMC), Sodium carboxy methyl cellulose (NaCMC), carbomers, chitosan, plant gums etc. The hydrophilic matrix-formers alone or in combination with other excipients form gels in situ on coming in contact with biological fluids which control the drug release. The present review gives a detailed account on the factors to be considered in the design of hydrophilic matrix systems, formulation of hydrophilic matrix tablets, in vitro and in vivo evaluation methods and advances in the design of hydrophilic matrix tablets. This review further focuses on the development of oral controlled drug delivery systems using hydrophilic matrix carriers in 20th century.

Preparation of alginate/vermiculite composite functionalized with silanol group for controlled drug delivery: Effect of CaCl2 concentration, release kinetics, cytotoxicity, and antimicrobial activities

In this study, alginate/vermiculite (Alg/VMT) hydrogel with 3-aminopropyl triethoxysilane (Alg/VSN) and tetraethoxysilane (Alg/VS) synthesized with various concentrations of CaCl2 (10 %–15 %–20 % M) to extend the release of 6-Aminopenicillanic acid (AP). Composites characterized by XRD, FTIR and BET. The result of Alg/VS composite shows an excellent loading of 243.90 mg/g through AP intercalated in the VMT layer. The equilibrium and Kinetic studies indicated that AP adsorption on Alg/VS and Alg/VSN was heterogeneous with chemical interaction. The in-vitro release Alg/VS showed a rapid burst release of 14 % in the first half an hour and only 75 % of the drug remained in the composite. Whereas, the in-vitro release Alg/VSN showed substantially less burst release with the cumulative release of 9 % (in the first 0.5 h). In-vitro release kinetics in the presence of CaCl2 concentrations showed that maximum 19 % of AP released within 12 h. The kinetic release was followed by a controlled release pattern (Korsmeyer-Peppas model) with Fick's law mechanism. The composites behaved as barriers against cell growth and had better biocompatibility against standard strains of Pseudomonas aeruginosa and Methicillin-Resistant Staphylococcus. MTT assay results from per cent cell viability composites modified by silanol groups were 96 % the means samples were nontoxic. The types of newly synthesized composites were able to finely decrease cell toxicity and improve AP release in vitro.

PEGylation of Mesoporous Silica Nanoparticles for Drug Delivery Applications

Mesoporous silica nanoparticles (MSNs) and PEGylated mesoporous silica nanoparticles (PEG-MSNs) were synthesized and characterized for potential targeted drug delivery applications. In this study, MSNs were synthesized via a sol-gel process to investigate in vitro drug release efficacy and subsequently PEGylated to impart colloidal stability and biocompatibility for future mouse model experiment. Comprehensive characterization techniques, including Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Brunauer-Emmett-Teller (BET) analysis, and zeta potential measurements were employed. SEM analysis revealed uniformly distributed spherical nanoparticles with smooth surfaces, while FTIR confirmed the successful PEGylation in the surface of MSNs. BET analysis also indicated a reduction in surface area, pore volume, and pore size upon PEGylation, suggesting that PEG chains influence the nanoparticle structure. Zeta potential measurements showed a shift from negative to positive surface charge post-PEGylation, indicating improved colloidal stability. Drug loading and release studies utilizing doxorubicin hydrochloride (DOX) demonstrated a controlled release profile, with MSNs exhibiting a higher cumulative release compared to PEG-MSNs over 24 h. These findings underscore the potential of PEG-MSNs for controlled drug delivery, offering advantages such as reduced systemic toxicity and enhanced therapeutic efficacy for PEG-MSNs nanocarrier in the animal studies due to their increased colloidal stability.

Nanofibers Membrane Loaded with Titanium Oxide and Rifampicin as Controlled Drug Delivery System for Wound Dressing Applications

Nanofibers Membrane Loaded with Titanium Oxide and Rifampicin as Controlled Drug Delivery System for Wound Dressing Applications

Multifunctional magneto-plasmonic lipogel based on peptide hydrogel for application in combined cancer therapy.

Supramolecular hydrogels, particularly low-molecular-weight peptide hydrogels, are promising drug delivery systems due to their ability to change the solubility, targeting, metabolism and toxicity of drugs. Magneto-plasmonic liposomes, in addition to being remotely controllable with the application of an external magnetic field, also increase the efficiency of encapsulated drug release through thermal stimulation, for example, with magnetic and optical hyperthermia. Thus, the combination of those two materials-giving magneto-plasmonic lipogels-brings together several functionalities, among which are hyperthermia and spatiotemporally controlled drug delivery. In this work, a novel dehydrodipeptide hydrogelator was synthesised, and the respective hydrogel was functionalized with magneto-plasmonic liposomes. After individually characterising the components with regard to their rheological, spectroscopic and magnetic properties, the magneto-plasmonic lipogel was equally characterised and evaluated concerning its ability to deliver drugs in a controlled fashion. To this end, the response of the 5(6)-carboxyfluorescein-loaded magneto-plasmonic lipogel to near-infrared light was assessed. The results showed that the system is a proper carrier of hydrophilic drugs and allows to envisage photo-responsive drug delivery. These facts, together with the magnetic guidance and hyperthermia capabilities of the developed composite gel, may pave the way to a new era in the treatment of cancer and other diseases.

Visible-Light-Induced Diselenide-Crosslinked Polymeric Micelles for ROS-Triggered Drug Delivery.

To synthesize an effective and versatile nano-platform serving as a promising carrier for controlled drug delivery, visible-light-induced diselenide-crosslinked polyurethane micelles were designed and prepared for ROS-triggered on-demand doxorubicin (DOX) release. A rationally designed amphiphilic block copolymer, poly(ethylene glycol)-b-poly(diselenolane diol-co-isophorone diisocyanate)-b-poly(ethylene glycol) (PEG-b-PUSe-b-PEG), which incorporates dangling diselenolane groups within the hydrophobic PU segments, was initially synthesized through the polycondensation reaction. In aqueous media, this type of amphiphilic block copolymer can self-assemble into micellar aggregates and encapsulate DOX within the micellar core, forming DOX-loaded micelles that are subsequently in situ core-crosslinked by diselenides via a visible-light-triggered metathesis reaction of Se-Se bonds. Compared with the non-crosslinked micelles (NCLMs), the as-prepared diselenide-crosslinked micelles (CLMs) exhibited a smaller particle size and improved colloidal stability. In vitro release studies have demonstrated suppressed drug release behavior for CLMs in physiological conditions, as compared to the NCLMs, whereas a burst release of DOX occurred upon exposure to an oxidation environment. Moreover, MTT assay results have revealed that the crosslinked polyurethane micelles displayed no significant cytotoxicity towards HeLa cells. Cellular uptake analyses have suggested the effective internalization of DOX-loaded crosslinked micelles and DOX release within cancer cells. These findings suggest that this kind of ROS-triggered reversibly crosslinked polyurethane micelles hold significant potential as a ROS-responsive drug delivery system.

Nano-Bio Interfaces: Pioneering Targeted Approaches for Disease Treatment and Prevention

Nanotechnology has emerged as a pivotal force in biomedical research, offering groundbreaking solutions for disease treatment and prevention through the integration of nanoscience with biology. This review explores the multifaceted applications of nano-bio interfaces in revolutionizing therapeutic interventions and public health strategies. At the forefront of innovation, nanomaterial-based drug delivery systems demonstrate unparalleled precision and efficacy in targeted drug delivery, minimizing systemic toxicity and maximizing therapeutic outcomes. Furthermore, the development of multifunctional nanoparticles capable of simultaneous drug delivery and diagnostic imaging enables real-time monitoring of treatment responses, heralding a new era of personalized medicine. Nano-bio interfaces also play a crucial role in advancing vaccine development and immunotherapies, with nanoparticle-based vaccine platforms offering enhanced antigen delivery and immune stimulation for robust and durable immune responses against infectious diseases and cancer. In the realm of disease prevention, antimicrobial nanomaterials provide effective strategies for infection control, while nanovaccines and prophylactic drug delivery systems offer tailored solutions for mitigating the spread of infectious agents. Through a comprehensive exploration of these pioneering approaches, this review, we believe, highlights the transformative potential of nano-bio interfaces in reshaping the landscape of disease treatment and prevention.

Flaxseed (Linum usitatissimum) mucilage: A versatile stimuli–responsive functional biomaterial for pharmaceuticals and healthcare

The present review is novel as it discusses the main findings of researchers on the topic and their implications, as well as highlights the emerging research in this particular area and its future prospective. The seeds of Flax (Linum usitatissimum) extrude mucilage (FSM) that has a diverse and wide range of applications, especially in the food industry and as a pharmaceutical ingredient. FSM has been blended with several food and dairy products to improve gelling ability, optical properties, taste, and user compliance. The FSM is recognized as a foaming, encapsulating, emulsifying, suspending, film–forming, and gelling agent for several pharmaceutical preparations and healthcare materials. Owing to stimuli (pH) –responsive swelling–deswelling characteristics, high swelling indices at different physiological pHs of the human body, and biocompatibility, FSM is considered a smart material for intelligent, targeted, and controlled drug delivery applications through conventional and advanced drug delivery systems. FSM has been modified through carboxymethylation, acetylation, copolymerization, and electrostatic complexation to get the desired properties for pharma, food, and healthcare products. The present review is therefore devoted to the isolation techniques, structural characterization, highly valuable properties for food and pharmaceutical industries, preclinical and clinical trials, pharmacological aspects, biomedical attributes, and patents of FSM.

Cubosomes and hexosomes stabilized by sorbitan monooleate as biocompatible nanoplatforms against skin metastatic human melanoma

Nanoparticles have become versatile assets in the medical field, providing notable benefits across diverse medical arenas including controlled drug delivery, imaging, and immunological assays. Among these, non-lamellar lipid nanoparticles, notably cubosomes and hexosomes, showcase remarkable biocompatibility and stability, rendering them as optimal choices for theranostic applications. Particularly, incorporating edge activators like sodium taurocholate enhances the potential of these nanoparticles for dermal and transdermal drug delivery, overcoming the stratum corneum, a first line of defense in our skin. This study reports on the formulation of monoolein-based cubosomes and hexosomes incorporating taurocholate and stabilized by Span 80 and co-encapsulating Chlorin e6 and coenzyme QH for photodynamic therapy in skin metastatic melanoma. The formulations were optimized using small-angle X-ray scattering, and cryo-transmission electron microscopy confirmed the presence of cubosomes or hexosomes, depending on the ratio between taurocholate and Span 80. Furthermore, the co-loaded nanoparticles exhibited high encapsulation efficiencies for both Ce6 and the coenzyme QH. In vitro studies on human melanoma cells (Me45) demonstrated the biocompatibility and photodynamic activity of the loaded formulations. These findings show the possibility of formulating more biocompatible cubosomes and hexosomes for photodynamic therapy in skin cancer treatment.

A Comprehensive Guide to Hydrogel-Based Controlled Drug Delivery for Cancer Treatment

Common kinds of chemotherapy may cause harm to normal cells and tissues. Localised chemotherapy, unlike systemic chemotherapy, can lessen side effects by providing a consistent supply of chemotherapeutic chemicals directly to the tumour location. This emphasises the importance of controlled-release biodegradable hydrogels as chemotherapeutic drug delivery systems. This study looks at employing hydrogels as drug delivery methods for HCC, including thermosensitive, pH-sensitive, photosensitive, dual-sensitive, and glutathione-responsive hydrogels. Hydrogel-based drug delivery systems outperform traditional systemic chemotherapy in cancer treatment. Cancer immunotherapy has emerged as the new paradigm for cancer treatment. The development and discovery of new therapeutic molecules has increased the use of immunotherapy in clinical studies. This article discusses the current state of functional hydrogels for effective cancer immunotherapy. First, we will discuss the fundamental principles of cancer immunotherapy and the benefits of employing hydrogels to implement these mechanisms. Finally, we briefly explore the existing issues and potential applications of hydrogels for effective cancer immunotherapy. Keywords: Cancer, Hydrogel-based controlled drug delivery system, postoperative radiotherapy, chemotherapy, Immunotherapy.

Understanding X-ray-induced isomerisation in photoswitchable surfactant assemblies.

Dynamic, responsive materials can be built using photosurfactants (PS) that self-assemble into ordered nanostructures, such as micelles or liquid crystals. These PS contain photoswitchable groups, such as azobenzene (Azo) or, more recently, arylazopyrazoles (AAPs), which change shape and polarity on photoisomerisation between the E and Z states, thus changing the self-assembled structure. Small-angle X-ray scattering (SAXS) is a powerful technique to probe the morphology of PS and can be used to measure the mechanisms of structural changes using in-situ light irradiation with rapid, time-resolved data collection. However, X-ray irradiation has been shown previously to induce Z-to-E isomerisation of Azo-PS, which can lead to inaccuracies in the measured photostationary state. Here, we investigate the effect of light and X-ray irradiation on micelles formed from two different PS, containing either an Azo or AAP photoswitch using SAXS with in-situ light irradiation. The effect of X-ray irradiation on the Z isomer is shown to depend on the photoswitch, solvent, concentration and morphology. We use this to create guidelines for future X-ray experiments using photoswitchable molecules, which can aid more accurate understanding of these materials for application in solar energy storage, catalysis or controlled drug delivery.

Starch nanoparticle preparation by the nanoprecipitation technique: Effects of formulation parameters

This study investigates how key formulation parameters influence the formation of starch nanoparticles using the nanoprecipitation technique. When loaded with different compounds, starch nanoparticles present a promising option for controlled drug delivery in food, biomedical, and pharmaceutical applications. The work thoroughly examines factors such as polymer concentration, NaOH concentration, solvent ratios, stirring speed, injection flow, and properties of the non-solvent phase. Characterization is conducted using dynamic light scattering, laser Doppler electrophoresis, and scanning electron microscopy, followed by statistical analysis. Increasing the stirring speed notably decreases nanoparticle size, yielding dimensions of 161.5±2.1 nm, 157.6±2.5 nm, and 136.0±0.8 nm at 500, 700, and 900 rpm, respectively. Higher starch concentrations slightly increase the zeta potential of starch nanoparticles to values of −1.97±0.4 mV, −3.1±0.7 mV, and −3.9±1.5 mV for concentrations of 0.5 %, 1 %, and 2 %, respectively. This charge can be attributed to the hydroxyl functional groups in starch monomers. The study also assesses the stability of starch nanoparticles at different pH levels (4, 7.4, and 9) and explores the use of cryoprotectants during freeze-drying. Remarkably, nanoparticles show enhanced stability at pH 7.4, maintaining their initial sizes over six weeks. Cryoprotectants, even in small amounts, effectively preserve nanoparticle size post-freeze-drying. By adjusting formulation parameters, researchers can tailor the physicochemical characteristics of nanoparticles to achieve specific sizes and ensure stability.

Correction: Fabrication and evaluation of chitosan nanoparticles/sodium alginate composite dressings for controlled drug delivery of tetracycline in wound healing

Correction: Fabrication and evaluation of chitosan nanoparticles/sodium alginate composite dressings for controlled drug delivery of tetracycline in wound healing

Porous egg microparticles for controllable drug delivery and oncotherapy

AbstractBaicalein (BAI) extracted from Chinese herb has been proved to increase the sensitivity of tumor cells to gemcitabine (GEM) and effectively solve the problem of drug resistance of tumor cells. Nevertheless, intravenous administration often leads to intolerance of patients and side effects. In this paper, we introduced egg‐based porous microparticles for controllable drug delivery and oncotherapy, which avoided frequent intravenous administration. The interconnected porous structure endowed the microparticles with the capacity of loading sufficient drugs and releasing in a controllable way by adjusting the concentration and proportion of egg white and yolk. We have demonstrated that the cell viability of drug delivery system group was less than 50%, while the single drug group was more than 70%, which indicated that the co‐delivery of GEM and BAI could significantly reduce the proliferation of cells. These features indicated that the egg porous microparticles are ideal for controllable drug delivery and oncotherapy.

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.

Cancer Treatment Using Nanofibers: A Review.

Currently, the number of patients with cancer is expanding consistently because of a low quality of life. For this reason, the therapies used to treat cancer have received a lot of consideration from specialists. Numerous anticancer medications have been utilized to treat patients with cancer. However, the immediate utilization of anticancer medicines leads to unpleasant side effects for patients and there are many restrictions to applying these treatments. A number of polymers like cellulose, chitosan, Polyvinyl Alcohol (PVA), Polyacrylonitrile (PAN), peptides and Poly (hydroxy alkanoate) have good properties for the treatment of cancer, but the nanofibers-based target and controlled drug delivery system produced by the co-axial electrospinning technique have extraordinary properties like favorable mechanical characteristics, an excellent release profile, a high surface area, and a high sponginess and are harmless, bio-renewable, biofriendly, highly degradable, and can be produced very conveniently on an industrial scale. Thus, nanofibers produced through coaxial electrospinning can be designed to target specific cancer cells or tissues. By modifying the composition and properties of the nanofibers, researchers can control the release kinetics of the therapeutic agent and enhance its accumulation at the tumor site while minimizing systemic toxicity. The core-shell structure of coaxial electrospun nanofibers allows for a controlled and sustained release of therapeutic agents over time. This controlled release profile can improve the efficacy of cancer treatment by maintaining therapeutic drug concentrations within the tumor microenvironment for an extended period.

Finite element method for natural convection flow of Casson hybrid (Al2O3–Cu/water) nanofluid inside H-shaped enclosure

The fundamental problem in electronic cooling systems is the implementation of a cavity such that it can be used to provide localized cooling to specific components, such as CPUs or GPUs, enhancing their performance and longevity. It can also be used in microfluidic devices for controlled drug delivery, where precise control of fluid flow is crucial. The present article numerically explores the free convection non-Newtonian Casson hybrid nanofluid phenomena that occur within an H-shaped cavity while heated from the middle. The heating efficiency and heat flow in a cavity are influenced by perpendicular hot walls that connect two vertical closed channels. A numerical solution is obtained by implementing the Galerkin finite element method to solve the partial differential equation. The numerical outcomes are depicted on the contour of streamlines and isotherms for different parameters in the following ranges: 0.1 ≤ η ≤ 0.4, 0.005≤ϕhp≤0.020, 0.1 ≤ γ ≤ 2, and 103 ≤ Ra ≤ 106 at fixed Pr = 6.2. In addition, line graphs show rate of heat transfer within the enclosure using the average Nusselt number for these parameters. Increased aspect ratios (η = 0.4) result in a minimal rate of heat transfer enhancement, whereas decreasing η leads to a significantly higher average Nusselt number and maximum heat transfer within the cavity. The convective rate of heat transfer increases with the presence of hybrid nanoparticles inside an H-shaped cavity for all Rayleigh numbers. The rotation of the Casson hybrid nanofluid also rises as the volume ratio of nanoparticles increases. For a fixed aspect ratio (A.R) of 0.1, the heat dissipation is 6.91% at a lower ϕhp value of 0.005 at a fixed Ra value of 105. However, it increases to 7.072% for a higher ϕhp value of 0.02 at Ra = 105. With increasing Ra number, ϕhp, and γ, the number NuAve increases.

Synthesis and rheological analyzes of temperature and light sensitive gels comprising amphiphilic azobenzene polymers, chitosan and pluronic F127

AbstractThis study investigates the reinforcement of pluronic (PF127) based temperature responsive hydrogels with photosensitive functionalities to create smart and injectable materials. For this purpose, 4‐[4‐[(4‐phenyl)azo]phenoxy] methacrylate (PAzPMA) was synthesized and further polymerized via reversible addition‐fragmentation chain transfer (RAFT) polymerization. The structures of the copolymers were characterized by several techniques such as Fourier‐transform infrared (FT‐IR), nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). The azobenzene‐functionalized copolymer was combined with P127 solid polymer in micelle form and with P127 micelles in solid form to obtain PF127‐AzoMx and PF127‐AzoPx gels, respectively. When the temperature profiles of the PF127‐AzoMx and PF127‐AzoPx systems were compared with PF127, sol–gel phase transition were shifted to lower temperatures due to stronger hydrophobic interactions. Additionally, different concentrations of N,N,N‐trimethyl chitosan (f‐chitosan) were added to the gel systems and their rheological properties were investigated by exposing them to UV light. It has been observed that the presence and concentration of f‐chitosan are important for the variation of the interactions' strength between the micelles. The study highlights the potential of multifunctional hydrogels for specific biomedical applications that combine sensitivity to both thermal and optical stimuli for controlled drug delivery and tissue engineering purposes.

Synthesis of stimuli-responsive copolymeric hydrogels for temperature, reduction and pH-controlled drug delivery

Stimuli-responsive copolymeric hydrogels (CH) are synthesized for controlled drug delivery. Oxidized glycyrrhizic acid is connected to acrylamide through Schiff base reaction, which is then copolymerized with N,N-bis (acryloyl) cystamine and N-isopropylacrylamide by free-radical polymerization for the loading of 5-fluorouracil with a loading efficiency of 96.7 %. The lower critical solution temperature of the CH is 39.14 °C. The N-isopropylacrylamide unit in the CH is sensitive to temperature, endowing the CH with temperature sensitivity. The carboxyl groups of oxidized glycyrrhizic acid can be deprotonated in alkaline solutions, and the electrostatic repulsions between the resultant carboxylate can cause swelling of the CH. The disulfide bond (S–S) of the N,N-bis (acryloyl) cystamine unit can be reduced to sulfhydryl (–SH) by glutathione, and thus the CH is also reduction-sensitive. Therefore, temperature, reduction and pH-controlled delivery of 5-fluorouracil from the CH is achieved. Cytotoxicity assay reveals that the drug-free hydrogels have good biocompatibility while the CH shows high cytotoxicity against human hepatoma SMMC-7721 cells, and the cell viability is only 25 % at the CH concentration of 1 mg mL−1.