pH-responsive Drug Delivery Research Articles

Fabrication of Flexible pH-Responsive Agarose/Succinoglycan Hydrogels for Controlled Drug Release.

Agarose/succinoglycan hydrogels were prepared as pH-responsive drug delivery systems with significantly improved flexibility, thermostability, and porosity compared to agarose gels alone. Agarose/succinoglycan hydrogels were made using agarose and succinoglycan, a polysaccharide directly isolated from Sinorhizobium meliloti. Mechanical and physical properties of agarose/succinoglycan hydrogels were investigated using various instrumental methods such as rheological measurements, attenuated total reflection–Fourier transform infrared (ATR-FTIR) spectroscopic analysis, X-ray diffraction (XRD), and field-emission scanning electron microscopy (FE-SEM). The results showed that the agarose/succinoglycan hydrogels became flexible and stable network gels with an improved swelling pattern in basic solution compared to the hard and brittle agarose gel alone. In addition, these hydrogels showed a pH-responsive delivery of ciprofloxacin (CPFX), with a cumulative release of ~41% within 35 h at pH 1.2 and complete release at pH 7.4. Agarose/succinoglycan hydrogels also proved to be non-toxic as a result of the cell cytotoxicity test, suggesting that these hydrogels would be a potential natural biomaterial for biomedical applications such as various drug delivery system and cell culture scaffolds.

Photo- and pH-responsive drug delivery nanocomposite based on o-nitrobenzyl functionalized upconversion nanoparticles

A near infrared (NIR) and pH dual-responsive nanocomposite, composed of a lanthanide-doped upconversion nanoparticle (UCNP) core and a transformable poly-o-nitrobenzyl shell, was prepared by the distillation precipitation polymerization and template method. The poly-o-nitrobenzyl shell can undergo hydrophobic-hydrophilic transformation upon an irradiation of 980 nm, rendering the capability of NIR-activated drug release. The anticancer drug, doxorubicin (DOX), can be loaded into these nanocomposites with a loading efficiency of 7.23 wt%. Furthermore, pH responsiveness caused by the hydrogen bond and charge interactions between DOX and nanocapsules can trigger the release of drugs at low pH. Under visible light irradiation and neutral (pH 7.4) conditions, the cumulative release of DOX was only 8.35% after 300 min, while it reached 59.5% under the synergistic effect of NIR irradiation and acidic conditions. The Baker-Lonsdale model was used to describe the drug release kinetics of this system, and the diffusion coefficient (3DCs/r02C0) and R2 under different conditions were determined to be 4.15 × 10−6 and 0.98 (pH 7.4 and visible light), 2.64 × 10−5 and 0.99 (NIR light), 3.26 × 10−5 and 0.97 (pH 4.5 and visible light), 2.59 × 10−4 and 0.99 (pH 4.5 and NIR light), respectively. This controlled release feature makes the nanocomposite a promising therapeutic agent for treating diseases.

A pH-responsive mesoporous silica nanoparticles-based drug delivery system with controlled release of andrographolide for OA treatment.

Andrographolide (AG) has favorable anti-inflammatory and antioxidative capacity. However, it has low bioavailability due to high lipophilicity and can be easily cleared by the synovial fluid after intra-articular injection, leading to low therapeutic efficiency in osteoarthritis (OA). Herein, we designed a nano-sized pH-responsive drug delivery system (DDS) for OA treatment by using modified mesoporous silica nanoparticles (MSNs) with pH-responsive polyacrylic acid (PAA) for loading of AG to form AG@MSNs-PAA nanoplatform. The nanoparticles have uniform size (∼120 nm), high drug loading efficiency (22.38 ± 0.71%) and pH-responsive properties, beneficial to sustained release in OA environment. Compared with AG, AG@MSNs-PAA showed enhanced antiarthritic efficacy and chondro-protective capacity based on IL-1β-stimulated chondrocytes and anterior cruciate ligament transection-induced rat OA model, as demonstrated by lower expression of inflammatory factors and better prevention of proteoglycan loss. Therefore, the AG@MSNs-PAA nanoplatform may be developed as a promising OA-specific and on-demand DDS.

Dual-drug delivery system based on the hydrogels of alginate and sodium carboxymethyl cellulose for colorectal cancer treatment

To improve the efficacy of chemotherapy and relieve the pain associated with colorectal cancer, a dual-drug delivery system (DDDS) is proposed. In this system, methotrexate (MTX) loaded CaCO3 (CaCO3/MTX) and aspirin (Asp) are co-entrapped in the hydrogels of alginate (Alg) and sodium carboxymethyl cellulose (CMC) crosslinked with Ca2+. The hydrogels can protect the anti-cancer drug of MTX from being absorbed in stomach and small intestine and ensure their efficacy at the target site of colorectum. More importantly, dual pH-responsive drug delivery can be achieved by the DDDS. Because the pH varies at small intestine and colorectum of human body, dual pH-responsive delivery of Asp and MTX can be achieved at the two organs, respectively, in response to ambient pH. These finding are of significant importance for medical science and pharmaceutics.

Simultaneous surface functionalization and drug loading: A novel method for fabrication of cellulose nanocrystals-based pH responsive drug delivery system

Herein, a novel strategy for surface functionalization and drug loading of cellulose nanocrystals (CNCs) through formation of hydrazone bonds between functionalized CNCs and aldehyde group containing polyethylene glycol (CHO-PEG)/anticancer drug doxorubicin (DOX) was reported for the first time. DOX could be loaded on PEGylated CNCs with high capacity and released from drug complexes (P-CNCs-D) with pH dependent behavior. The biological evaluation results demonstrated that drug carriers (CNCs-EBO-NH) showed negative cytotoxicity while DOX could be transported into cells and exhibits desirable anticancer effects. As compared with other method, the method developed in this work is rather simple and effective and can be achieved for simultaneous for surface functionalization and drug loading in a one-pot route. This work will open a new avenue for fabrication of various multifunctional composites based on other carbohydrate polymers or materials and to explore their applications in biomedical fields.

Polydopamine loaded fluorescent nanocellulose–agarose hydrogel: A pH-responsive drug delivery carrier for cancer therapy

Herein, PDA-Py–CNC–AG composite hydrogel was developed by agarose, polydopamine and pyrene fluorophore labeled nanocellulose through interpenetrating polymer network strategy, which exhibited both fluorescent characteristics and pH responsive properties. Moreover, the adhesion to cells and controlled release performance to drug of the developed hydrogel was enhanced by the incorporation of polydopamine. As compared with single network hydrogel, the composite hydrogel yield a drug release up to 86.3% through a sustained drug release for 8 days at pH 5.5, the cytotoxicity was also enhanced obviously. More significantly, the fluorescent chromophore, pyrene was covalently linked to the amino group of amino-derivative nanocellulose, thereby providing attractive fluorescence properties to the synthesized hydrogel. Therefore, this composite hydrogel with multifunctional properties provides enhanced ability to cope with complexed tumor microenvironment and other challenging applications.

Synthesis and surface modification of mesoporous metal-organic framework (UiO-66) for efficient pH-responsive drug delivery and lung cancer treatment

This paper applied mesoporous metal-organic frameworks (MOFs) of UiO-66 particles for pH-responsive doxorubicin (DOX) delivery and cancer treatment. Mesoporous structured UiO-66 MOFs were synthesized, and carboxymethylcellulose (CMC) was loaded for sensitive pH response and also as a linker to encapsulate the chemotherapeutic drug of DOX. The composite of UiO-66/CMC@DOX was synthesized, and the loading capacity was as high as 45 μg DOX per mg of the carrier. The structure and crystalization of the UiO-66 MOFs were determined by the Transmitting Electron Microscope (TEM) and x-ray diffraction methods, while the loading of CMC and DOX was inspected by Fourier Transform InfraRed (FT-IR) and UV–vis spectroscopy. The DOX release from UiO-66/CMC@DOX was tested under different pH at 37 °C. The DOX accumulative release could reach 78% under the pH of 5. A lower pH was more favorable for DOX release due to the CMC shrinking and higher DOX solubility in an acidic environment. The cytotoxicity study indicated that, under the DOX concentration of 4 μg ml−1, the A549 cell (Lung Carcinoma Cell Line) viability of UiO-66/CMC was 28%, which was lower than that from free DOX solution (47%). UiO-66 MOFs were demonstrated to be an efficient drug delivery carrier for chemotherapeutic drug and release.

PH-responsive mesoporous silica drug delivery system, its biocompatibility and co-adsorption/co-release of 5-Fluorouracil and Naproxen

A pH-responsive drug delivery system composed of N-(propyl)aniline (N-ANI) modified mesoporous silica nanoparticles as a carrier, and β-cyclodextrin (β-CD) as a cap was prepared and investigated. The system was studied for co-adsorption and co-delivery of two different drugs; an anticancer drug 5-fluorouracil (5-FU), and anti-inflammatory agent naproxen (NAP). Detailed adsorption study of the drugs themselves as well as in their mutual mixture was performed. The drug release experiments were realized in simulated body fluid (pH = 7.4) and slightly acidic medium (pH = 5) imitating the pH of tumor affected area. The experiments showed, that at physiological pH 7.4, the prepared drug delivery system released no drug, at slightly acidic medium (pH = 5) the β-CD caps were loosened, and drugs were released (88.5% and 98.7% for 5-FU and NAP, respectively). To investigate the efficiency of the designed system for the delivery in biological environment, the biocompatibility and cytotoxicity experiments were performed using U87 MG and SKBR3 cancer cells by fluorescence microscopy, flow-cytometry, MTT. apoptotic and CAM assays.

Preparation of carbon dots-hematite quantum dots-loaded hydroxypropyl cellulose-chitosan nanocomposites for drug delivery, sunlight catalytic and antimicrobial application

In this project, we studied the thermal and chemical method for the synthesis of carbon dots (CDs)/Hematite (α-Fe2O3) quantum dots and the preparation of hydroxypropyl cellulose cross-linked chitosan (HPCCS) and ulvan (UN) was performed by chemical method. Carbon dots/α-Fe2O3 quantum dots with size distribution of 3–5 nm were completely encapsulated in the HPCCS/UN NPs to obtain composites, which indicated unique characteristics with respect to antimicrobial, pH-responsive and optical properties. The CDs-HQDs/HPCCS/UN nanocomposites exhibited a single-excitation (440 nm), dual-emission fluorescence property (505 nm and 628 nm for green and red light from CDs-HQDs and HPCCS/UN NPs). The nanocomposites played as a pH-responsive drug delivery process to release ulvan at a fast rate in pH 7.4 buffer solution but at a slow rate in low pH solutions. The CDs-HQDs/HPCCS/UN nanocomposites gained the highest photocatalytic activity for degrading 4-chlorophenol (4-CPh) as a pollutant (>98% during 70 min under sunlight irradiation). Moreover, the nanocomposites indicated great inhibitory influences towards bacterial and fungal.

Facile solvothermal synthesis of monodisperse superparamagnetic mesoporous Fe3O4 nanospheres for pH-responsive controlled drug delivery

In the present work, monodisperse Fe3O4 nanospheres with typical mesoporous structures and superparamagnetic characteristics were synthesized through a simple solvothermal approach. Various characterization experiments including SEM, TEM, XRD, XPS, BET and SQUID were performed to investigate in detail the morphology, microstructure, composition and physicochemical properties of the prepared Fe3O4 nanospheres. It was found that the average diameter of Fe3O4 nanospheres was determined to be about 207.3 nm with a relatively narrow size distribution. The analysis of nitrogen adsorption/desorption isotherms indicated that Fe3O4 nanospheres represented typical mesoporous structures having a surface area of 20.68 m2/g. The magnetic property measurements demonstrated that the synthesized nanospheres behaved as superparamagnetic with a high saturation magnetization of 97.5 emu/g. Most importantly, the mesoporous Fe3O4 nanospheres could be utilized as a potential anti-cancer drug carrier for doxorubicin hydrochloride (DOX). The drug loading capacity and in vitro drug release behavior of DOX in phosphate buffered solutions under different pH values (4.0, 5.5 and 7.4) were examined. The results showed that the developed drug delivery system based on mesoporous Fe3O4 nanospheres exhibited a high drug loading capacity and a controlled drug release behavior.

Pollen-like silica nanoparticles as a nanocarrier for tumor targeted and pH-responsive drug delivery

Aptamer modified hollow silica nanoparticles with pollen structure (plSP@aptamer) were synthesized and used as a nanocarrier for tumor targeted and pH-responsive drug delivery. The 292 ± 14 nm interior void in diameter together with 11.8 nm surface pore size of plSP@aptamer nanoparticles contributed to a high drug loading efficiency of 0.509 g g−1. Furthermore, the drug delivery system was pH-responsive, and the releasing efficiency was up to 87.5% at pH of 5. The special spikes of this plSP@aptamer nanoparticles acted as “entry claws” to enhanced the interaction between cell and drug nanocarriers and then increased the internalization rate of drug vehicles. The cell uptake assay suggested that most of doxorubicin (DOX)@plSP@aptamer nanoparticles can escape form lysosome and located in nuclei of MCF-7 cells. The targeted performance testing showed that almost no DOX@plSP@aptamer were internalized by normal cells, indicating a high specificity of our drug vehicles. The cytotoxicity of nanoparticles was also investigated, the plSP@aptamer particles had excellent biocompatibility and the cell viability was nearly 100%. After loaded with DOX, DOX@plSP@aptamer showed great potential in targeted therapy of tumors, and only 4.2% MCF-7 cells were viable.

A pH-Responsive Supramolecular Drug Delivery System Constructed by Cationic Pillar[5]arene for Enhancing Antitumor Activity.

Drug delivery systems have good biocompatibiliy and low side effects for cancer treatment, but overcoming high efficiency of drug-loading and the drug-targeting controlled release still remains challenging. In this work, supramolecular vesicles, with pH-triggering effect, have been successfully constructed for drug delivery, which are fabricated by the complexation between a cationic pillar[5]arene (DAWP5) and a sodium dodecyl sulfonate (SDS) in aqueous solution. Drug-loading and releasing results demonstrated that anticancer drug doxorubicin (DOX) could be loaded efficiently by such cationic vesicles in neutral condition, and the drug release could be controlled in the simulated weak acid environment of tumor cells. Moreover, the vesicles had low cytotoxicity to normal human cell (L02), while the DOX-loaded vesicles could significantly enhance the cytotoxicity of free DOX for normal cell L02 and four tested tumor cells (Hela, HepG2, MGC-803 and T24). Especially for HepG2, after 24 h incubation time, IC50 of DOX-loaded vesicles was only 0.79 μM, about 23% of that of DOX (3.43 μM). These results suggested that such novel vesicles have promising potential to construct nano-drug delivery systems for various biomedical applications.

PH/Thermo-Responsive Grafted Alginate-Based SiO2 Hybrid Nanocarrier/Hydrogel Drug Delivery Systems.

We report the preparation of mesoporous silica nanoparticles covered by layer by layer (LbL) oppositely charged weak polyelectrolytes, comprising poly(allylamine hydrochloride) (PAH) and a sodium alginate, highly grafted by N-isopropylacrylamide/N-tert-butylacrylamide random copolymers, NaALG-g-P(NIPAM90-co-NtBAM10) (NaALG-g). Thanks to the pH dependence of the degree of ionization of the polyelectrolytes and the LCST-type thermosensitivity of the grafting chains of the NaALG-g, the as-prepared hybrid nanoparticles (hNP) exhibit pH/thermo-responsive drug delivery capabilities. The release kinetics of rhodamine B (RB, model drug) can be controlled by the number of PAH/NaALG-g bilayers and more importantly by the environmental conditions, namely, pH and temperature. As observed, the increase of pH and/or temperature accelerates the RB release under sink conditions. The same NaALG-g was used as gelator to fabricate a hNP@NaALG-g hydrogel composite. This formulation forms a viscous solution at room temperature, and it is transformed to a self-assembling hydrogel (sol-gel transition) upon heating at physiological temperature provided that its Tgel was regulated at 30.7 °C, by the NtBAM hydrophobic monomer incorporation in the side chains. It exhibits excellent injectability thanks to its combined thermo- and shear-responsiveness. The hNP@NaALG-g hydrogel composite, encapsulating hNP covered with one bilayer, exhibited pH-responsive sustainable drug delivery. The presented highly tunable drug delivery system (DDS) (hNP and/or composite hydrogel) might be useful for biomedical potential applications.

A pH-sensitive drug delivery system based on hyaluronic acid co-deliver doxorubicin and aminoferrocene for the combined application of chemotherapy and chemodynamic therapy

Doxorubicin is a broad-spectrum antineoplastic drug used in tumor therapy, its clinical application is limited by side effects on normal tissues. In this article, a pH-responsive drug delivery system (NPs(DOX/AFc)) with co-delivers doxorubicin (DOX) and aminoferrocene (AFc) was prepared by a two-step synthesis method including the oxidation of hyaluronic acid and Schiff base reaction. NPs(DOX/AFc) can be used in combination therapy of chemodynamic therapy (CDT) and chemotherapy (CT), thus the dosage of the chemotherapeutic drug DOX was reduced. The drug release behavior of NPs(DOX/AFc) in vitro showed that acid-responsive drug releases under the endosomal/lysosomal environment were 56.5 % of DOX and 61.8 % of AFc. In vitro toxicity experiments showed that DOX and AFc had synergistic effects (CI = 0.878). The results of intracellular ROS measurement and the mitochondrial membrane potential analysis showed that in tumor cells NPs(DOX4/AFc) induced more production of reactive oxygen species and more loss of the mitochondrial membrane potential. In short, this co-delivery system based on polymer prodrugs provides a new idea for the combined application of CT and CDT.

Polydopamine/keratin complexes as gatekeepers of mesoporous silica nanoparticles for pH and GSH dual responsive drug delivery

Mesoporous silica nanoparticles (MSNs) have attracted considerable attention for drug delivery due to their tunable pore sizes and morphologies, excellent biocompatibility, and ideal sites to bind other chemical groups. In this study, MSNs were first coated with polydopamine (PDA) by mussel-inspired polymerization and then conjugated with keratin via iron(III)-mediated coordination chemistry. The doxorubicin (DOX)-loaded MSNs(MSNs-DOX@PDA@keratin) exhibited pH and glutathione (GSH) dual-responsive drug release behavior as well as higher toxicity against tumor cells with lower toxicity on normal cells. These drug carriers could be uptaken by the tumor cells through endocytosis, having great potential in drug delivery applications.

Design of poly-l-glutamic acid embedded mesoporous bioactive glass nanospheres for pH-stimulated chemotherapeutic drug delivery and antibacterial susceptibility

In this research, a core-shell type pH-responsive poly-l-glutamic acid embedded mesoporous bioactive glass nanospheres (MBAG/PLGA) was designed via aminosilane functionalization of MBAG using 3-aminopropyltriethoxysilane (APTES). The formation of MBAG/PLGA was well dispersed in an aqueous medium and demonstrated high drug loading efficacy and enhanced drug delivery rate. Daunomycin (DAN) was considered as a model chemotherapeutic drug for loading and release study. The cumulative in vitro release of DAN from DAN loaded MBAG/PLGA (MBAG/PLGA@DAN) was observed to be pH-dependent and, the DAN release rate was much higher at pH ∼ 5.5 compared to pH at 7.4. The modified Kirby-Bauer microbial assay results showed that the MBAG is a potential antimicrobial agent and susceptibility for Gram-negative bacteria is observed to be much higher than Gram-positive ones. Advanced characterization studies such as SEM coupled with EDX, HRTEM, FTIR, XPS, TGA, XRD, and BET analysis were performed to support the findings of this research. Overall, these results demonstrated that MBAG/PLGA is a promising candidate for a pH-responsive localized drug delivery system in bioconjugate science.

Poly(N-vinylcaprolactam) and Salicylic Acid Polymeric Prodrug Grafted onto Medical Silicone to Obtain a Novel Thermo- and pH-Responsive Drug Delivery System for Potential Medical Devices.

New medical devices with anti-inflammatory properties are critical to prevent inflammatory processes and infections in medical/surgical procedures. In this work, we present a novel functionalization of silicone for medical use with a polymeric prodrug and a thermosensitive polymer, by graft polymerization (gamma rays), for the localized release of salicylic acid, an analgesic, and anti-inflammatory drug. Silicone rubber (SR) films were functionalized in two stages using graft polymerization from ionizing radiation (60Co). The first stage was grafting poly(N-vinylcaprolactam) (PNVCL), a thermo-sensitive polymer, onto SR to obtain SR-g-PNVCL. In the second stage, poly(2-methacryloyloxy-benzoic acid) (P2MBA), a polymeric prodrug, was grafted to obtain (SR-g-PNVCL)-g-P2MBA. The degree of functionalization depended on the concentrations of monomers and the irradiation dose. The films were characterized by attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy/energy-dispersive X-ray spectrometry (SEM–EDX), thermogravimetric analysis (TGA), and contact angle. An upper critical solution temperature (UCST) of the films was demonstrated by the swelling degree as a temperature function. (SR-g-PNVCL)-g-P2MBA films demonstrated hydrolysis-mediated drug release from the polymeric prodrug, pH, and temperature sensitivity. GC–MS confirmed the presence of the drug (salicylic acid), after polymer hydrolysis. The concentration of the drug in the release media was quantified by HPLC. Cytocompatibility and thermo-/pH sensitivity of functionalized medical silicone were demonstrated in cancer and non-cancer cells.

Hybrid mesoporous nanoparticles with highly integrated polydopamine for pH-responsive membrane permeation and drug delivery

By the synergy of surface amines/catechols, polydopamine (PDA)-based nanomaterials are appealing in inducing wet-adhesion and membrane permeabilization for efficient intracellular delivery of drugs, especially those with low membrane permeability. Herein, hybrid mesoporous silica nanoparticles with highly integrated PDA on the pore walls were developed using ionic liquid as an organic template. Small particle diameters (~30–50 nm), high surface area (549 m2 g−1), and abundant mesopores (~ 5 nm), were achieved. Modification of arginine and pH-sensitive sheddable PEG was realized to construct a membrane-lytic surface and a protective coating, respectively. The nanocarriers can mediate efficient drug loading, sustained release, and cytosolic delivery of a model BCS Class III drug (cytarabine) after efficient lysosomal escape. Moreover, the intrinsic photothermal conversion property of PDA can enhance the cancer cell inhibition. The results show the potential of highly integrated PDA in porous nanocarriers for overcoming intracellular obstacles of drug delivery.

Conjugated Polymer Nanoparticles Based on Copper Coordination for Real-Time Monitoring of pH-Responsive Drug Delivery.

Metal coordination-driven composite systems have excellent stability and pH-responsive ability, making them suitable for specific drug delivery in physiological conditions. In this study, an anionic conjugated polymer PPEIDA with a poly(p-phenylene ethynylene) backbone and iminodiacetic acid (IDA) side chains is used as a drug carrier to construct a class of pH-responsive nanoparticles, PPEIDA-Cu-DOX conjugated polymer nanoparticles (CPNs), by taking advantage of the metal coordination interaction of Cu2+ with PPEIDA and the drug doxorubicin (DOX). PPEIDA-Cu-DOX CPNs have high drug loading and encapsulation efficiency (EE), calculated to be 54.30 ± 1.10 and 95.80 ± 0.84%, respectively. Due to the good spectral overlap, Förster resonance energy transfer (FRET) takes place between PPEIDA and the drug DOX, which enables the observation of the loading and the release of DOX from CPNs in an acidic environment by monitoring fluorescence emission changes. Therefore, PPEIDA-Cu-DOX CPNs can also be used in real-time cell imaging to monitor drug release in addition to delivering DOX targeting tumor cells. Compared with free DOX, PPEIDA-Cu-DOX CPNs show a similar inhibition to tumor cells and lower toxicity to normal cells. Our results demonstrate the feasibility and potential of constructing pH-responsive CPNs via metal-ligand coordination interactions for cancer treatment.

A core-shell structured alginate hydrogel beads with tunable thickness of carboxymethyl cellulose coating for pH responsive drug delivery

pH-responsive core-shell structured composite hydrogel beads, composed of a alginate (ALG) core coated with carboxymethyl cellulose (CMC) shell (ALG@CMC), were prepared by using in-situ gel preparation technology as a drug delivery system. An anti-inflammatory drug, indomethacin was loaded into the formed hydrogels as a model drug. The resulting gel samples were characterized by Fourier transforms infrared (FTIR) spectroscopy, thermo-gravimetric (TG) analysis, and scanning electron microscopy (SEM). The mechanical stability of all samples in phosphate buffered solution (PBS, pH 7.4) was approximately measured through oscillation experiments. Swelling and controlled drug release behaviors of ALG@CMC beads compared with ALG were studied in simulating gastric fluid of pH 1.2 or intestinal fluid of pH 7.4 at 37 °C. Oscillation experiments proved that the mechanical stability of ALG@CMC beads could be significantly improved by the CMC shell layer. The swelling and drug release behaviors revealed that the swelling and drug release rate of ALG@CMC beads were obviously slower than that of simple-ALG and both have significant pH responsiveness. The cumulative drug release from ALG, ALG@CMC-1, ALG@CMC-2 and ALG@CMC-3 was about 100%, 67%, 46% and 37% in simulated intestinal fluid of pH 7.4, respectively, while the drug release reached only about 2.0% in simulating gastric fluid of pH 1.2 within 720 min. These developed materials could potentially be employed as a pH-responsive drug delivery device in vivo.