Thermo/pH Dual Responsive Mixed‐Shell Polymeric Micelles Based on the Complementary Multiple Hydrogen Bonds for Drug Delivery

Thermo/pH dual responsive mixed‐shell polymeric micelles based on multiple hydrogen bonding were prepared by self‐assembly of diaminotriazine‐terminated poly(?‐caprolactone) (DAT‐PCL), uracil‐terminated methoxy poly(ethylene glycol) (MPEG‐U), and uracil‐terminated poly(N‐vinylcaprolactam) (PNVCL‐U) at room temperature. PCL acted as the core and MPEG/PNVCL as the mixed shell. Increasing the temperature, PNVCL collapsed and enclosed the PCL core, while MPEG penetrated through the PNVCL shell, thereby leading to the formation of MPEG channels on the micelles surface. The low cytotoxicity of the mixed micelles was confirmed by an MTT assay against BGC‐823 cells. Studies on the in vitro drug release showed that a much faster release rate was observed at pH 5.0 compared to physiological pH, owing to the dissociation of hydrogen bonds. Therefore, the mixed‐shell polymeric micelles would be very promising candidates in drug delivery systems.     

带有可调通道的嵌段共聚物胶束对药物的控制释放

用聚丙烯酸叔丁酯-b-聚乙二醇(PtBA45-b-PEG114)和聚丙烯酸叔丁酯-b-聚4-乙烯基吡啶(PtBA60-b-P4VP80)制备了复合胶束. 该胶束在pH=2.5的酸性水溶液中形成以PtBA为核, PEG和P4VP为壳的稳定球型结构. 在pH=12时, 壳层的P4VP链段变为疏水, 塌缩在PtBA的核上形成内壳, PEG链段继续保持溶解状态, 与成核的PtBA连接并穿过塌陷的P4VP内壳, 形成胶束的冠, 由于PEG处于溶解状态, 其分子链间有比较大的空隙, 可以控制一些小分子通过, 在胶束的表面形成通道. 该通道类似于生物膜的蛋白通道, 可以控制PtBA核与外界进行能量或物质交换的速度. 以布洛芬为模型分子, 负载在胶束内进行药物控制释放研究的结果表明, 胶束表面的通道可以起到明显控制布洛芬释放速度的作用, 并且药物的释放速度与通道在胶束表面的比例成正比.     

Fabrication of uniform magnetic nanocomposite spheres with a magnetic core/mesoporous silica shell structure

A novel kind of magnetic core/mesoporous silica shell nanospheres with a uniform particle diameter of ca. 270 nm was synthesized. The inner magnetic core endues the whole nanoparticle with magnetic properties, while the outer mesoporous silica shell shows high enough surface area and pore volume. The synthesized material is expected to be applied to targeted drug delivery and multiphase separation. The storage and release of ibuprofen into and from the pore channels of the mesoporous silica shell, as a typical example, are demonstrated.     

Preparation of pH- and thermo-sensitive chitosan-PNIPAAm core–shell nanoparticles and evaluation as drug carriers

Environmentally sensitive polysaccharide nanoparticles (NPs) were prepared by in situ polymerization of N-isopropylacrylamide (NIPAAm) monomer in the presence of chitosan (CS) micelles. First, CS was found to develop a cationic micelle-like structure in the acetic acid solution when its concentration was increased to above the critical micelle concentration, as evidenced by fluorescence and TEM. When the NIPAAm was polymerized in the CS micelle solution by using potassium persulfate as initiator, the produced PNIPAAm with anionic chain end(s) became hydrophobic, as long as the reaction temperature was above its phase transition temperature; and therefore it would diffuse into the hydrophobic core of the CS micelles, producing CS-PNIPAAm core–shell NPs. Increasing the feeding amount of NIPAAm increased the monomer conversion and therefore the particle size; yet it decreased the surface zeta potential. Moreover, the CS-PNIPAAm NPs were sensitive to both pH value and temperature. For the study of drug release properties, doxycycline hyclate was used as a model drug and loaded into the NPs at pH 4.5 and 25 °C. The result illustrated that these NPs had a continuous drug release behavior up to 1 week, depending on the pH value and temperature. In addition, enzyme or hydrogen peroxide capable of degrading CS shell was added in the solution to facilitate the drug release.     

Effects of a lysophosphatidylcholine and a phosphatidylcholine on the morphology of taurocholic acid-based mixed micelles as determined by small-angle X-ray scattering

We previously showed that Caco-2 cell absorption of β-carotene from taurocholic acid (TA)-based mixed micelles differed depending on the composition of the micelles. In this study, the shapes and sizes of TA-based mixed micelles, that is, mixed micelles of TA, 1-oleoyl-rac-glycerol (MG), oleic acid (OLA), and either 1-palmitoyl-sn-glycero-3-phosphocholine (MPPC; i.e., a lysophospholipid) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC; i.e., a phospholipid) (60:3:1:0.75–12) were determined by using small-angle X-ray scattering (SAXS). We found that increasing the ratio of MPPC in mixed micelles of TA, MG, OLA, and MPPC was responsible for the previously observed enhanced β-carotene absorption by Caco-2 cells and changed the micelle shape from core–shell spherical to core–shell ellipsoidal. In contrast, increasing the ratio of POPC in mixed micelles of TA, MG, OLA, and POPC was responsible for the suppressed β-carotene absorption by the cells, changed the micelle shape from core–shell spherical to core–shell ellipsoidal to core–shell cylindrical, and caused a rapid increase in micelle volume. These results will be useful for understanding the mechanisms that mediate β-carotene absorption by cells and for developing technologies to improve the intestinal absorption of lipophilic components of drugs and nutrients.     

聚[2-(甲基丙烯酰氧)乙基三甲基氯化铵]/阿拉伯胶复凝聚法十二醇微胶囊的制备

将聚[2-(甲基丙烯酰氧)乙基三甲基氯化铵](PMTC)和阿拉伯胶(GA)在一定条件下进行了复凝聚,并对影响复凝聚实验的壁材配比、壁材浓度、离子强度等因素进行了考察.实验结果表明,PMTC与GA配比为1/3.22,壁材总浓度为4%时复凝聚效率最高;体系中不同浓度的氯化钠的存在会对复凝聚起到不同程度的抑制作用.在实验确定的最佳复凝聚条件下以有机小分子化合物十二醇作为芯材进行了包覆,制备了不同壁芯比例的微胶囊.对微胶囊的包覆率及载药量进行了测量,并对它们的释放行为进行了考察.包覆有十二醇的复合微胶囊大小一般在几微米.随着壁材与芯材比例的增大,胶囊载药量逐渐降低,微胶囊释放十二醇的速率明显变小,但包覆率却无明显变化规律.     

Fabrication of polymeric micelles with core–shell–corona structure for applications in controlled drug release

Thermo-responsive polymeric micelles of poly (ethylene glycol)-b-poly(2-hydroxyethyl methacrylate-g-lactide)-b-poly(N-isopropylacrylamide) (PEG-P(HEMA-PLA)-PNIPAM) with core–shell–corona structure were fabricated for applications in controlled drug release. The graft copolymer of PEG-P(HEMA-PLA)-PNIPAM was self-assembled into core–shell micelles with a densely PLA core and mixed PEG/PNIPAM shells at 25 °C in aqueous media. By increasing the temperature above the lower critical solution temperature of PNIPAM, these core–shell micelles could be converted into core–shell–corona micelles because of the collapse of PNIPAM block on the PLA core as the inner shell and the soluble PEG block stretching outside as the outer corona. Anticancer drug doxorubicin (DOX) was loaded in the polymeric micelles as a model drug. Compared with polymeric micelles formed by liner PEG-b-PLA-b-PNIPAM triblock copolymer, these polymeric micelles exhibited higher loading capacity, and release of DOX from the polymeric micelles with core–shell–corona structure was well-controlled.     

Complex micelles formed from two diblock copolymers for applications in controlled drug release

Double‐responsive core‐shell‐corona complex micelles for applications in drug release were formed from self‐assembly of two diblock copolymers PtBA‐b‐ PNIPAM and PtBA‐b‐P4VP. The two diblock copolymers coaggregated into core‐shell complex micelles in acidic water with the hydrophobic PtBA blocks as the common core and soluble PNIPAM/P4VP blocks as the mixed shell. Increasing temperature or pH value, the micelles converted into core‐shell‐corona micelles because of the collapse of PNIPAM or P4VP blocks as the inner shell and soluble P4VP or PNIPAM chains stretching outside as the outer corona. The anti‐inflammation drug naproxen (NAP) was loaded as the model drug in micelles in acidic water and released because of the ionization of NAP in alkaline solutions. Compared with pure core‐shell micelles, release of NAP from core‐shell‐corona complex micelles avoided the burst diffusion and the release rate is more easily controlled by tuning the composition of the mixtures or by adjusting the pH of the medium. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1804–1810, 2009     

Thermosensitive t‐PLA‐b‐PNIPAAm tri‐armed star block copolymer nanoscale micelles for camptothecin drug release

Thermosensitive polylactide‐block‐poly(N‐isopropylacrylamide) (t‐PLA‐b‐PNIPAAm) tri‐armed star block copolymers were synthesized by atom transfer radical polymerization (ATRP) of monomer NIPAAm using t‐PLA‐Cl as macroinitiator. The synthesis of t‐PLA‐Cl was accomplished by esterification of star polylactides (t‐PLA) with 2‐chloropropionyl chloride using trimethylolpropane as a center molecule. FT‐IR, ¹H NMR, and GPC analyses confirmed that the t‐PLA‐b‐PNIPAAm star block copolymers had well‐defined structure and controlled molecular weights. The block copolymers could form core‐shell micelle nanoparticles due to their hydrophilic‐hydrophobic trait in aqueous media, and the critical micelle concentrations (CMC) were from 6.7 to 32.9 mg L^?1, depending on the system composition. The as‐prepared micelle nanoparticles showed reversible phase changes in transmittance with temperature: transparent below low critical solution temperature (LCST) and opaque above the LCST. Transmission electron microscopy (TEM) observations revealed that the micelle nanoparticles were spherical in shape with core‐shell structure. The hydrodynamic diameters of the micelle nanoparticles depended on copolymer compositions, micelle concentrations and media. MTT assays were conducted to evaluate cytotoxicity of the camptothecin‐loaded copolymer micelles. Camptothecin drug release studies showed that the copolymer micelles exhibited thermo‐triggered targeting drug release behavior, and thus had potential application values in drug controlled delivery. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4429–4439     

Polyvinylpyrrolidone–polycaprolactone block copolymer micelles as nanocarriers of anti-TB drugs

A range of polyvinylpyrrolidone–polycaprolactone diblock copolymers with varying chain lengths were synthesized by Atom Transfer Radical Polymerisation (ATRP) using bromo-polycaprolactone as macroinitiator and copper(I) bromide/bipyridine catalytic system. The copolymers self-assembled in solution into core–shell micelles with sizes varying from 150 to 205 nm and critical micelle concentration of the order of 10⁻⁵ to 10⁻⁶ M. Front line anti-Tuberculosis drugs Rifampicin (RIF), Pyrazinamide (PZA) and Isoniazid (INH) were successfully encapsulated within the micelle hydrophobic core singly or in dual combination. The effect of length of hydrophobic and hydrophilic segments on drug loading, micelle size and drug release was investigated. Determination of binding constants showed that RIF binds more strongly to the micelle core than PZA and INH, leading to highest drug loading content. All drugs were released in vitro (PBS solution at 37 °C) in a sustained manner with zero-order kinetics and followed the order INH > PZA > RIF.     

Temperature‐Responsive Mixed‐Shell Polymeric Micelles for the Refolding of Thermally Denatured Proteins

We have fabricated a mixed‐shell polymeric micelle (MSPM) that closely mimics the natural molecular chaperone GroEL? GroES complex in terms of structure and functionality. This MSPM, which possesses a shared PLA core and a homogeneously mixed PEG and PNIAPM shell, is constructed through the co‐assembly of block copolymers poly(lactide‐b‐poly(ethylene oxide) (PLA‐b‐PEG) and poly(lactide)‐b‐poly(N‐isopropylacryamide) (PLA‐b‐PNIPAM). Above the lower critical solution temperature (LCST) of PNIPAM, the MSPM evolves into a core–shell–corona micelle (CSCM), as a functional state with hydrophobic PNIPAM domains on its surface. Light scattering (LS), TEM, and fluorescence and circular dichroism (CD) spectroscopy were performed to investigate the working mechanism of the chaperone‐like behavior of this system. Unfolded protein intermediates are captured by the hydrophobic PNIPAM domains of the CSCM, which prevent harmful protein aggregation. During cooling, PNIPAM reverts into its hydrophilic state, thereby inducing the release of the bound unfolded proteins. The refolding process of the released proteins is spontaneously accomplished by the presence of PEG in the mixed shell. Carbonic anhydrase B (CAB) was chosen as a model to investigate the refolding efficiency of the released proteins. In the presence of MSPM, almost 93 % CAB activity was recovered during cooling after complete denaturation at 70 °C. Further results reveal that this MSPM also works with a wide spectrum of proteins with more‐complicated structures, including some multimeric proteins. Given the convenience and generality in preventing the thermal aggregation of proteins, this MSPM‐based chaperone might be useful for preventing the toxic aggregation of misfolded proteins in some diseases.     

Shell cross-linked stearic acid grafted chitosan oligosaccharide self-aggregated micelles for controlled release of paclitaxel

Stearic acid grafted chitosan oligosaccharide (CSO-SA) with different degree of amino substitution (SD) was synthesized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The critical micelle concentration (CMC) of CSO-SA with different SD was about 0.06, 0.04, 0.01 mg/ml, respectively. With the increase of micelle concentration, the micelle size decreased, and the zeta potential increased. On the other hand, with the increase of SD of CSO-SA, the micelle size and zeta potential decreased due to the increased hydrophobic interaction of SA and the reduced free amino groups. To increase the stability of the micelle in vivo and controll drug release, the shells of micelles were cross-linked by glutaraldehyde. By controlling the molar ratio of CSO-SA to glutaraldehyde, the cross-linking of intra-micelle could be reached, and the nanoparticle with smaller size than that of its initial micelle was obtained. Paclitaxel was then used as model drug to incorporate into the micelles, and the surfaces of the micelles were further cross-linked by glutaraldehyde to form drug loaded and shell cross-linked nanoparticles. The effects of drug loading, SD of CSO-SA and cross-link degree on the size, zeta potential, drug entrapment efficiency and in vitro drug release behavior of micelles and its cross-linked nanoparticles were investigated. The higher drug entrapment efficiencies (above 94%) were observed in all case. The charged amounts of drug did not affect the drug release behavior. The drug release rate decreased with the increase of SD of CSO-SA and cross-link degree.     

Modulating the catalytic activity of Au/micelles by tunable hydrophilic channels

Polymeric micelles with a polystyrene core, poly(acrylic acid)/poly(4-vinyl pyridine) (PAA/P4VP) complex shell and poly(ethylene glycol) & poly(N-isopropylacrylamide) (PEG & PNIPAM) mixed corona were synthesized and used as the supporter for the gold nanoparticles (GNs). It was concluded from the result of ¹H NMR characterization that hydrophilic channels formed around PEG chains when PNIPAM collapsed above its lower critical solution temperature. The density of the channels in the corona can be tuned by changing the weight ratios of PEG chains to PNIPAM chains. The GNs were set in the PAA/P4VP complex layer and the catalytic activity of the GNs can be modulated by the channels. The catalytic activity increased with increasing the density of the channels in the corona. Meanwhile, the whole Au/micelle nanoparticles were stabilized by the extended PEG chains.     

Hollow nanoparticles prepared from pH‐responsive template polymer micelles

Water‐soluble crosslinked hollow nanoparticles were prepared using pH‐responsive anionic polymer micelles as templates. The template micelles were formed from pH‐responsive diblock copolymers (PAMPS‐PAaH) composed of the poly(sodium 2‐(acrylamido)‐2‐methylpropanesulfonate) and poly(6‐(acrylamido)hexanoic acid) blocks in an aqueous acidic solution. The PAMPS and PAaH blocks form a hydrophilic anionic shell and hydrophobic core of the core‐shell polymer micelle, respectively. A cationic diblock copolymer (PEG‐P(APTAC/CEA)) with the poly(ethylene glycol) block and random copolymer block composed of poly((3‐acrylamidopropyl)trimethylammonium chloride) containing a small amount of the 2‐(cinnamoyl)ethylacrylate photo‐crosslinkable unit can be adsorbed to the anionic shell of the template micelle due to electrostatic interaction, which form a core‐shell‐corona three‐layered micelle. The shell of the core‐shell‐corona micelle is formed from a polyion complex with anionic PAMPS and cationic P(APTAC/CEA) chains. The P(APTAC/CEA) chains in the shell of the core‐shell‐corona micelle can be photo‐crosslinked with UV irradiation. The template micelle can be dissociated using NaOH, because the PAaH blocks are ionized. Furthermore, electrostatic interactions between PAMPS and PAPTAC in the shell are screened by adding excess NaCl in water. The template micelles can be completely removed by dialysis against water containing NaOH and NaCl to prepare the crosslinked hollow nanoparticles. Transmission electron microscopy observations confirmed the hollow structure. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Core–Shell Hollow Microspheres of Magnetic Iron Oxide@Amorphous Calcium Phosphate: Synthesis Using Adenosine 5′‐Triphosphate and Application in pH‐Responsive Drug Delivery

Drug nanocarriers with magnetic targeting and pH‐responsive drug‐release behavior are promising for applications in controlled drug delivery. Magnetic iron oxides show excellent magnetism, but their application in drug delivery is limited by low drug‐loading capacity and poor control over drug release. Herein, core–shell hollow microspheres of magnetic iron oxide@amorphous calcium phosphate (MIO@ACP) were prepared and investigated as magnetic, pH‐responsive drug nanocarriers. Hollow microspheres of magnetic iron oxide (HMIOs) were prepared by etching solid MIO microspheres in hydrochloric acid/ethanol solution. After loading a drug into the HMIOs, the drug‐loaded HMIOs were coated with a protective layer of ACP by using adenosine 5′‐triphosphate (ATP) disodium salt (Na₂ATP) as stabilizer, and drug‐loaded core–shell hollow microspheres of MIO@ACP (HMIOs/drug/ACP) were obtained. The as‐prepared HMIOs/drug/ACP drug‐delivery system exhibits superparamagnetism and pH‐responsive drug‐release behavior. In a medium with pH 7.4, drug release was slow, but it was significantly accelerated at pH 4.5 due to dissolution of the ACP shell. Docetaxel‐loaded core–shell hollow microspheres of MIO@ACP exhibited high anticancer activity.     

Poly(ethylene glycol)-b-poly(epsilon-caprolactone) and PEG-phospholipid form stable mixed micelles in aqueous media

Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG(5000)-b-PCL(x)) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy poly(ethylene glycol) (PEG-DSPE), possess small size and high thermodynamic stability, raising their potential as long circulating carriers in the context of delivery of antineoplastic and antibiotic drugs. Formation of mixed polymeric micelles was confirmed using size exclusion chromatography and 1H NMR NOESY. Steady-state fluorescence measurements revealed depressed critical micellar concentrations indicative of a cooperative interaction between component hydrophobic blocks, which was quantified using the pseudophase model for micellization. Steady-state fluorescence measurements indicated that the mixed polymeric micelle cores possess intermediate micropolarity and high microviscosity. Pulsed field gradient spin-echo measurements were used to characterize micellar diffusion coefficients, which agree well with those obtained using dynamic light scattering. NOE spectra suggested that the hydrophobic polymer segments from individual components are in close proximity, giving evidence for the formation of a relatively homogeneous core. Contrary to one-component PEG(5000)-b-PCL(x) micelles, the mixed polymeric micelles could incorporate clinically relevant levels of the poorly water soluble antibiotic, amphotericin B (AmB). AmB encapsulation and release studies revealed an interesting composition-dependent interaction of the drug with the mixed polymeric micelle core.     

Facile strategy for synthesis of silica/polymer hybrid hollow nanoparticles with channels

The silica/polymer hybrid hollow nanoparticles with channels and gatekeepers were successfully fabricated with a facile strategy by using thermoresponsive complex micelles of poly(ethylene glycol)-b-poly(N-isopropylacrylamide) (PEG-b-PNIPAM) and poly(N-isopropylacrylamide)-b-poly(4-vinylpyridine) (PNIPAM-b-P4VP) as the template. In aqueous solution, the complex micelles (PEG-b-PNIPAM/PNIPAM-b-P4VP) formed with the PNIPAM block as the core and the PEG/P4VP blocks as the mixed shell at 45 °C and pH 4.0. After shell cross-linking by 1,2-bis(2-iodoethoxyl)ethane (BIEE), tetraethylorthosilicate (TEOS) selectively well-deposited on the P4VP block and processed the sol-gel reaction. When the temperature was decreased to 4 °C, the PNIPAM block became swollen and further soluble, and the PEG-b-PNIPAM block copolymer escaped from the hybrid nanoparticles as a result of swelled PNIPAM and weak interaction between PEG and silica at pH 4.0. Therefore, the hybrid hollow silica nanoparticles with inner thermoresponsive PNIPAM as gatekeepers and channels in the silica shell were successfully obtained, which could be used for switchable controlled drug release. In the system, the complex micelles, as a template, could avoid the formation of larger aggregates during the preparation of the hybrid hollow silica nanoparticles. The thermoresponsive core (PNIPAM) could conveniently control the hollow space through the stimuli-responsive phase transition instead of calcination or chemical etching. In the meantime, the channel in the hybrid silica shell could be achieved because of the escape of PEG chains from the hybrid nanoparticles.     

Physicochemical characterization of phospholipid solubilized mixed micelles and a hydrodynamic model of interfacial fluorescence quenching

Mixed micelles of solubilized dimyristoyl phosphatidylcholine (DMPC) and the zwitterionic detergent dodecyldimethylammoniopropane sulfonate are characterized employing time-resolved fluorescence quenching (TRFQ), electron spin resonance (ESR), and surface tensiometry toward the goal of investigating interfacial reactions using these micelles as host reaction media. The properties measured are the micelle aggregation numbers, interfacial hydration index, microviscosity, and the critical micelle concentrations for various molar fractions, XDMPC, of DMPC, 0相似文献   

Gas‐forming poly(ethylene glycol)‐b‐poly(L‐lactic acid) micelles

In this study, a novel drug‐carrying micelle composed of methoxy poly(ethylene glycol) (mPEG)‐b‐poly(L‐lactic acid) (PLLA) with gas‐forming carbonate linkage was fabricated. Here, the gas‐forming carbonate linkage was formed by the chemical coupling of the terminal hydroxyl group of the PLLA block and benzyl chloroformate (BC). mPEG‐b‐PLLA‐BC was self‐organized in aqueous solution: the PEG block on the hydrophilic outer shell and the PLLA‐BC block in the hydrophoboic innor core. The cleavage of carbonate linkage by hydrolysis and formation of carbon dioxide nanobubbles in the micellar core enabled an accelerated release of the encapsulated anticancer drug (doxorubicin: DOX) from the mPEG‐b‐PLLA‐BC micelles. The amount of drug (DOX) released from the mPEG‐b‐PLLA‐BC micelle was higher than that from the conventional mPEG‐b‐PLLA micelle, which allowed for increased in vitro toxicity against KB tumor cells. Copyright © 2013 John Wiley & Sons, Ltd.     

Core‐shell structure microcapsules with dual pH‐responsive drug release function

We report dual pH‐responsive microcapsules manufactured by combining electrostatic droplets (ESD) and microfluidic droplets (MFD) techniques to produce monodisperse core (alginate)‐shell (chitosan) structure with dual pH‐responsive drug release function. The fabricated core‐shell microcapsules were size controllable by tuning the synthesis parameters of the ESD and MFD systems, and were responsive in both acidic and alkaline environment, We used two model drugs (ampicillin loaded in the chitosan shell and diclofenac loaded in the alginate core) for drug delivery study. The results show that core‐shell structure microcapsules have better drug release efficiency than respective core or shell particles. A biocompatibility test showed that the core‐shell structure microcapsules presented positive cell viability (above 80%) when evaluated by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The results indicate that the synthesized core‐shell microcapsules were a potential candidate of dual‐drug carriers.