Synthesis of chitosan‐based thermo‐ and pH‐responsive porous nanoparticles by temperature‐dependent self‐assembly method and their application in drug release

In this research, thermo‐ and pH‐responsive chitosan‐based porous nanoparticles were prepared by the temperature‐dependent self assembly method. The chitosan‐graft‐poly(N‐isopropylacrylamide) (CS‐g‐PNIPAAm) copolymer solution was prepared through polymerization of N‐isopropylacrylamide (NIPAAm) monomer in the presence of chitosan (CS) solution using cerium ammounium nitrate as the initiator. Then, CS‐g‐PNIPAAm solution was diluted by deionized water and heated to 40 °C for CS‐g‐PNIPAAm self‐assembly. After that, CS‐g‐PNIPAAm assembled to form micelles in which shell layer was CS. Crosslinking agent was used to reinforce the micelle structure to form nanoparticle. The molar ratio of CS/NIPAAm in the feed mixture was changed to investigate its effect on structure, morphology, thermal‐ and pH‐responsive properties of the nanoparticles. TEM images showed that a porous structure of nanoparticles was developed. The synthesized nanoparticles carried positive charges on the surface and exhibited stimuli‐responsive properties, and their mean diameter thus could be manipulated by changing pH value and temperature of the environment. The nanoparticles showed a continuous release of the encapsulated doxycycline hyclate up to 10 days during an in‐vitro release experiment. These porous particles with environmentally sensitive properties are expected to be utilized in hydrophilic drug delivery system. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5126–5136, 2009     

Synthesis and characterization of stimuli‐responsive porous/hollow nanoparticles by self‐assembly of chitosan‐based graft copolymers and application in drug release

In this research, stimuli‐responsive porous/hollow nanoparticles were prepared by the self‐assembly method. First, chitosan‐graft‐poly(N‐isopropylacrylamide) (CS‐g‐PNIPAAm) copolymers were synthesized through polymerization of N‐isopropylacrylamide (NIPAAm) monomer in the presence of chitosan (CS) solution using ceric ammounium nitrate as the initiator. Then, the CS‐g‐PNIPAAm copolymers were dissolved in the acetic acid aqueous solution and heated to 40 °C to induce their self‐assembly. After CS‐g‐PNIPAAm assembled to form micelles, a cross‐linking agent was used to reinforce the structure to form nanoparticles. The molecular weight of grafted PNIPAAm on CS chains was changed to investigate its effect on the structure, morphology, thermo‐, and pH‐responsive properties of the nanoparticles. TEM images showed that a porous or hollow structure in the interior of nanoparticles was developed, depending on the medium temperature. The synthesized nanoparticles carried positive charges on the surface and exhibited stimuli‐responsive properties, and their mean diameter thus could be manipulated by changing the pH value and temperature of the environment. The nanoparticles showed a continuous release of the encapsulated doxycycline hyclate up to 10 days during an in vitro release experiment. These porous/hollow particles with environmentally sensitive properties are expected to be used in hydrophilic drug delivery system. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2377–2387, 2010     

Synthesis and properties of chitosan‐based thermo‐ and pH‐responsive nanoparticles and application in drug release

In this research, thermo‐ and pH‐responsive nanoparticles with an average diameter of about 50–200 nm were synthesized via the surfactant‐free emulsion polymerization. The thermal/pH dual responsive properties of these nanoparticles were designed by the addition of a pH sensitive monomer, acrylic acid (AA), to be copolymerized with N‐isopropylacrylamide (NIPAAm) in a chitosan (CS) solution. The molar ratio of CS/AA/NIPAAm in the feed was changed to investigate its effect on structure, morphology, thermal‐ and pH‐responsive properties of the nanoparticles. It was found that CS‐PAA‐PNIPAAm nanoparticles could be well dispersed in the aqueous solution and carried positive charges on the surface. The addition of thermal‐sensitive NIPAAm monomer affected the polymerization mechanism and interactions between CS and AA. The particle size of the nanoparticles was found to be varied with the composition of NIPAAm monomer in the feed. The synthesized nanoparticles exhibited stimuli‐responsive properties, and their mean diameter thus could be manipulated by changing pH value and temperature of the environment. The nanoparticles showed a continuous release of the encapsulated doxycycline hyclate up to 10 days during an in vitro release experiment. The environmentally responsive nanoparticles are expected to be used in many fields such as drug delivery system. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2798–2810, 2009     

Chitosan nanoparticles crosslinked by glycidoxypropyltrimethoxysilane for pH triggered release of protein

pH-responsive-chitosan nanoparticles for the control release of protein drug were prepared by combining two-step crosslinking method,in which chitosan was subsequently crosslinked by sodium tripolyphosphate(TPP)and glycidoxypropyltrimethoxysilane (GPTMS).Compared with TPP crosslinked chitosan particles,the two-step crosslinked nanoparticles were not only pH-responsive but also more stable in wide pH range.Fluorescein isothiocyanate(FITC)labeled anti-human-IgG antibody was used as a model protein drug for...     

Kinetic study of chitosan‐tripolyphosphate complex reaction and acid‐resistive properties of the chitosan‐tripolyphosphate gel beads prepared by in‐liquid curing method

Chitosan gel beads were prepared using an in‐liquid curing method by the ionotropic crosslinking with sodium tripolyphosphate. Crosslinking characteristics of the chitosan‐TPP beads were improved by the modification of in‐liquid curing mechanism of the beads in TPP solution. Chitosan gel beads cured in pH value lower than 6 were really ionic‐crosslinking controlled, whereas chitosan gel beads cured in pH values higher than 7 were coacervation‐phase inversion controlled accompanied with slightly ionic‐crosslinking dependence. According to the result, significantly increasing the ionic‐crosslinking density of chitosan beads could be achieved by transferring the pH value of the curing agent, TPP, from basic to acidic. The swelling behavior of various chitosan beads in acid appeared to depend on the ionic‐crosslinking density of the chitosan‐TPP beads that were deeply affected by the curing mechanism of the beads. The mechanism of chitosan‐TPP beads swollen in weak acid was chain‐relaxation controlled, while the mechanism of chitosan‐TPP beads swollen in strong acid seem to be not only chain‐relaxation but also chain‐scission controlled. Chitosan‐TPP beads prepared in acidic TPP solution decreased the chain‐scission ability due to the increase of ionic crosslinking density of the beads. By the transition of curing mechanism, the swelling degree of chitosan‐TPP beads was depressed, and the disintegration of chitosan‐TPP beads would not occur in strong acid. The mechanism of ionic‐crosslinking reaction of chitosan beads could be investigated by an unreacted core model, and the curing mechanism of the chitosan beads is mainly diffusion controlled when higher than 5% of chitosan was employed. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 1551–1564, 1999     

离子凝聚法制备负载流感疫苗的壳聚糖微球

采用三聚磷酸钠(TPP)作为离子交联剂, 应用离子凝聚法制备负载流感疫苗的壳聚糖微球. 筛选出壳聚糖起始质量分数为1%. TPP的浓度对壳聚糖微球的制备影响较大, 采用低浓度的TPP(200 μg/mL)制备的微球放置过夜均出现沉淀现象, 高浓度的TPP(800 μg/mL)在制备过程中出现絮状沉淀. 固化比影响微球的释放行为, 固化比为1∶1的微球爆炸式释放率达到90％, 固化比为1∶3的微球6 h后逐步释放, 12 h后释放率达到95％. 固化比为1∶5的微球6 h后没有明显的释放行为. 壳聚糖溶液的pH对微球的制备和释放没有显著的影响. 通过对负载流感疫苗的壳聚糖微球的制备条件和释放行为的研究结果表明, pH=5.6的壳聚糖溶液, 固化比为1∶3, TPP的质量浓度为400 μg/mL是较理想的流感疫苗壳聚糖微球的制备条件.     

Full polysaccharide chitosan‐CMC membrane and silver nanocomposite: synthesis,characterization, and antibacterial behaviors

Chitosan‐carboxymethyl cellulose (CMC) full polysaccharide membrane was prepared by cross‐linking of chitosan with CMC dialdehyde and subsequent reductive amination. CMC dialdehyde molecule was prepared by periodate oxidation of CMC and then applied as a cross‐linking agent to form a new membrane network. The properties of oxidized CMC were investigated by various methods such as Fourier transform infrared (FT‐IR) spectroscopy, ¹H NMR spectroscopy, and viscosity test. Then, novel chitosan‐CMC silver nanocomposite was prepared using chitosan‐CMC as a carrier. The structure of the chitosan‐CMC membrane and the silver nanocomposite were confirmed by FT‐IR spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA). TEM images indicate that the chitosan‐CMC nanocomposite comprises silver nanoparticles with diameters in the range of about 5–20 nm. The antibacterial studies of the nanocomposite were also evaluated. The chitosan‐CMC silver nanocomposite demonstrates good antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Copyright © 2016 John Wiley & Sons, Ltd.     

Synthesis of Imatinib‐loaded chitosan‐modified magnetic nanoparticles as an anti‐cancer agent for pH responsive targeted drug delivery

Targeted drug delivery is a promising approach to overcome the limitations of classical chemotherapy. In this respect, Imatinib‐loaded chitosan‐modified magnetic nanoparticles were prepared as a pH sensitive system for targeted delivery of drug to tumor sites by applying a magnetic field. The proposed magnetic nanoparticles were prepared through modification of magnetic Fe₃O₄ nanoparticles with chitosan and Imatinib. The structural, morphological and physicochemical properties of the synthesized nanoparticles were determined by different analytical techniques including energy‐dispersive X‐ray spectroscopy (EDS), field emission scanning electron microscopy (FESEM), Fourier‐transform infrared (FTIR) spectroscopy, high resolution transmission electron microscopy (HR‐TEM), vibrating sample magnetometry (VSM), X‐ray diffraction (XRD) and X‐ray photoelectron spectroscopy (XPS). UV/visible spectrophotometry was used to measure the Imatinib contents. Thermal stability of the prepared particles was investigated and their efficiency of drug loading and release profile were evaluated. The results demonstrated that Fe₃O₄@CS acts as a pH responsive nanocarrier in releasing the loaded Imatinib molecules. Furthermore, the Fe₃O₄@CS/Imatinib nanoparticles displayed cytotoxic effect against MCF‐7 breast cancer cells. Results of this study can provide new insights in the development of pH responsive targeted drug delivery systems to overcome the side effects of conventional chemotherapy.     

Chitosan nanoparticle as protein delivery carrier--systematic examination of fabrication conditions for efficient loading and release

Chitosan nanoparticles fabricated via different preparation protocols have been in recent years widely studied as carriers for therapeutic proteins and genes with varying degree of effectiveness and drawbacks. This work seeks to further explore the polyionic coacervation fabrication process, and associated processing conditions under which protein encapsulation and subsequent release can be systematically and predictably manipulated so as to obtain desired effectiveness. BSA was used as a model protein which was encapsulated by either incorporation or incubation method, using the polyanion tripolyphosphate (TPP) as the coacervation crosslink agent to form chitosan-BSA-TPP nanoparticles. The BSA-loaded chitosan-TPP nanoparticles were characterized for particle size, morphology, zeta potential, BSA encapsulation efficiency, and subsequent release kinetics, which were found predominantly dependent on the factors of chitosan molecular weight, chitosan concentration, BSA loading concentration, and chitosan/TPP mass ratio. The BSA loaded nanoparticles prepared under varying conditions were in the size range of 200-580nm, and exhibit a high positive zeta potential. Detailed sequential time frame TEM imaging of morphological change of the BSA loaded particles showed a swelling and particle degradation process. Initial burst released due to surface protein desorption and diffusion from sublayers did not relate directly to change of particle size and shape, which was eminently apparent only after 6h. It is also notable that later stage particle degradation and disintegration did not yield a substantial follow-on release, as the remaining protein molecules, with adaptable 3-D conformation, could be tightly bound and entangled with the cationic chitosan chains. In general, this study demonstrated that the polyionic coacervation process for fabricating protein loaded chitosan nanoparticles offers simple preparation conditions and a clear processing window for manipulation of physiochemical properties of the nanoparticles (e.g., size and surface charge), which can be conditioned to exert control over protein encapsulation efficiency and subsequent release profile. The weakness of the chitosan nanoparticle system lies typically with difficulties in controlling initial burst effect in releasing large quantities of protein molecules.     

Preparation of chitosan nanoparticles as carrier for immobilized enzyme

This work investigated the preparation of chitosan nanoparticles used as carriers for immobilized enzyme. The morphologic characterization of chitosan nanoparticles was evaluated by scanning electron microscope. The various preparation methods of chitosan nanoparticles were discussed and chosen. The effect of factors such as molecular weight of chitosan, chitosan concentration, TPP concentration, and solution pH on the size of chitosan nanoparticles was studied. Based on these results, response surface methodology was emploved. The results showed that solution pH, TPP concentration, and chitosan concentration significantly affected the size of chitosan nanoparticles. The adequacy of the predictive model equation for predicting the magnitude orders of the size of chitosan nanoparticles was verified effectively by the validation data. Immobilization conditions were investigated as well. The minimum particles size was about 42±5 nm under the optimized conditions. The optimal conditions of immobilization were as follow: one milligram of neutral proteinase was immobilized on chitosan nanoparticles for about 15 min at 40°C. Under the optimized conditions, the enzyme activity yield was 84.3%.     

Preparation and characterization of metronidazole‐loaded chitosan nanoparticles for drug delivery application

This study describes the preparation of mucoadhesive chitosan nanoparticles containing metronidazole (MZ) intended for colon‐specific delivery. The chitosan nanoparticles were prepared by the ionic gelation method and their in vitro properties were studied. The release profiles of MZ from the nanoparticles were determined by UV–Vis absorption measurement at λ_max 278 nm. Scanning electron microscopy was used for morphology observation. The nanoparticles exhibited mucoadhesive properties, which diminished with increasing drug content. The nanoparticles with a particle size range between 200 and 300 nm exhibited excellent mucoadhesive properties. The results show that the formulated nanoparticles have succeeded in controlling the release of MZ over a 12‐hr period. In conclusion, the release of MZ was found to be dependent upon the composition of the nanoparticles, the ratio of the components and possible particle size, as well as bioadhesive ability. Copyright © 2008 John Wiley & Sons, Ltd.     

壳聚糖纳米粒子荧光探针的制备和表征

通过低分子量的壳聚糖(LCS)聚阳离子与三聚磷酸钠(TPP)的静电作用制备纳米级壳聚糖微球,并利用壳聚糖链上丰富的氨基与荧光素异硫氰酸酯(FITC)反应从而制备纳米壳聚糖微球荧光探针(NFCS)。结果表明,当壳聚糖分子量为60000,LCS与TPP的质量比为6∶1时,可得到粒度均一的球形纳米粒子,平均粒径为40±3 nm。荧光倒置显微镜观察证实FITC结合到壳聚糖微球上。荧光光谱分析显示NFCS的最大激发波长、最大发射波长与游离态FITC无显著差异。光漂白实验证实NFCS的稳定性比游离态FITC有显著提高。     

Thermo‐ and pH‐induced self‐assembly of P(AA‐b‐NIPAAm‐b‐AA) triblock copolymers synthesized via RAFT polymerization

A series of environmentally sensitive ABA triblock copolymers with different block lengths were prepared by reversible addition‐fragmentation chain transfer (RAFT) polymerization from acrylic acid (AA) and N‐isopropylacrylamide (NIPAAm). The GPC and ¹H NMR analyses demonstrated the narrow molecular weight distribution and precise chemical structure of the prepared P(AA‐b‐NIPAAm‐b‐AA) triblock copolymers owing to the controlled/living characteristics of RAFT polymerization. The lower critical solution temperature (LCST) of the triblock copolymers could be tailored by adjusting the length of PAA block and controlled by the pH value. Under heating, the triblock copolymers underwent self‐assemble in dilute aqueous solution and formed nanoparticles revealed via TEM images. Physically crosslinked nanogels induced by inter‐/intra‐hydrogen bonding or core‐shell micelle particles thus could be obtained by changing environmental conditions. With a well‐defined structure and stimuli‐responsive properties, the P(AA‐b‐NIPAAm‐b‐AA) copolymer is expected to be employed as a nanocarrier for biomedical applications in controlled‐drug delivery and targeting therapy. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1109–1118     

Core–shell structure PEO/CS nanofibers based on electric field induced phase separation via electrospinning and its application

Core–shell structured PEO‐chitosan nanofibers have been produced from electric field inducing phase separation. Chitosan, a positive charged polymer, was dissolved in 50 wt % aqueous acetic acid and the amino group on polycation would protonize, which would endow chitosan electrical properties. Chitosan molecules would move along the direction of the electric field under the electrostatic force and formed the shell layer of nanofibers. Preparation process of core – shell structure is quite simple and efficient without any post‐treatment. The core–shell structure and existence of chitosan on the shell layer were confirmed before and after post‐treatment by TEM and further supported by SEM, FTIR, XRD, DSC, and XPS studies. Blending ratio of PEO and chitosan, molecular weight of chitosan for the mobility of chitosan are thought to be the key influence factors on formation of core–shell structure. Drug release studies show that the prepared core–shell structure nanofibers has a potential application in the biomedical fields involving drug delivery. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2298–2311     

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.     

Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery

This work investigates the polyanion initiated gelation process in fabricating chitosan-TPP (tripolyphosphate) nanoparticles in the size range of 100-250 nm intended to be used as carriers for the delivery of gene or protein macromolecules. It demonstrates that ionic gelation of cationic chitosan molecules offers a flexible and easily controllable process for systematically and predictably manipulating particle size and surface charge which are important properties in determining gene transfection efficacy if the nanoparticles are used as non-viral vectors for gene delivery, or as delivery carriers for protein molecules. Variations in chitosan molecular weight, chitosan concentration, chitosan to TPP weight ratio and solution pH value were examined systematically for their effects on nanoparticle size, intensity of surface charge, and tendency of particle aggregation so as to enable speedy fabrication of chitosan nanoparticles with predetermined properties. The chitosan-TPP nanoparticles exhibited a high positive surface charge across a wide pH range, and the isoelectric point (IEP) of the nanoparticles was found to be at pH 9.0. Detailed imaging analysis of the particle morphology revealed that the nanoparticles possess typical shapes of polyhedrons (e.g., pentagon and hexagon), indicating a similar crystallisation mechanism during the particle formation and growth process. This study demonstrates that systematic design and modulation of the surface charge and particle size of chitosan-TPP nanoparticles can be readily achieved with the right control of critical processing parameters, especially the chitosan to TPP weight ratio.     

Chitosan nanoparticles of 5-fluorouracil for ophthalmic delivery: characterization, in-vitro and in-vivo study

The aim of this investigation was to develop 5-fluorouracil (5-FU) loaded chitosan nanoparticles (CH-DNPs) for ophthalmic delivery. CH-DNPs were fabricated by ionotropic gelation mechanism using chitosan (CH) and a polyanion (TPP). The nanoparticles were smooth and spherical, confirmed by scanning electron microscopy (SEM) and atomic force microscope (AFM). CH/TPP mass ratio and TPP significantly changed the particles size morphology and encapsulation efficiency. The nanoparticles size ranged from approximately 114 to 192 nm and had a positive zeta potential (30±4 mV). The encapsulation efficiency, loading capacity and recovery of DNPs were 8.12-34.32%, 3.14-15.24% and 24.22 to 67% respectively. Physical characterization was done by Fourier transform infrared (FT-IR) and X-ray diffraction (XRD). No interaction was observed in between drug and polymer and crystallinity of drug was not changed in drug loaded nanoparticles. In-vitro release study of DNPs showed diffusion controlled release. Bioavailability study of batch CS9 was studied in rabbit eye and compare to 5-FU solution. 5-FU level was significantly higher in aqueous humor of rabbit eye. Ocular tolerance was studied in the eye of New Zealand rabbits and tested formulation was non-irritant with no sign of inflammation.     

O-羧甲基壳聚糖纳米微粒制备及对Ni~(2+)吸附研究

将壳聚糖与氯乙酸反应,通过控制反应条件制备了取代度为0.71的O-羧甲基壳聚糖,将改性后的O-羧甲基壳聚糖与多聚磷酸钠反应,制备了粒径分布在370-710nm的O-羧甲基壳聚糖纳米微粒,透射电镜观察表明该微粒呈球状,平均粒径为450nm.在此基础上研究了O-羧甲基壳聚糖纳米微粒对工业电镀镍废水Ni~(2+)吸附性能,考察了溶液pH、Ni~(2+)起始浓度、平衡吸附时间、粒径等因素的影响,结果表明:O-羧甲基壳聚糖微粒最佳吸附条件是Ni~(2+)溶液pH为8.0、Ni~(2+)溶液起始浓度为33.28mg/ml、平衡吸附时间为0.5h、粒径较小的O-羧甲基壳聚糖纳米微粒对Ni~(2+)的吸附量要大于粒径较大的吸附量.     

A visible light responsive azobenzene‐functionalized polymer: Synthesis,self‐assembly,and photoresponsive properties

A novel visible light responsive random copolymer consisting of hydrophobic azobenzene‐containing acrylate units and hydrophilic acrylic acid units has been prepared. The azobenzene molecule bearing methoxy groups at all four ortho positions is readily synthesized by one‐step conversion of diazotization. The as‐prepared polymer can self‐assemble into nanoparticles in water due to its amphiphilic nature. The tetra‐o‐methoxy‐substituted azobenzene‐functionalized polymer can exhibit the trans‐to‐cis photoswitching under the irradiation with green light of 520 nm and the cis‐to‐trans photoswitching under the irradiation with blue light of 420 nm in both solution and aggregate state. The morphologies of the self‐assembled nanoparticles are revealed by TEM and DLS. The controlled release of loaded molecules from the nanoparticles can be realized by adjusting pH value since the copolymer possesses pH responsive acrylic acid groups. The fluorescence of loaded Nile Red in the nanoparticles can be tuned upon the visible light irradiation. The reversible photoswitching of the azobenzene‐functionalized polymer under visible light may endow the polymer with wide applications without using ultraviolet light at all. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2768–2775     

Preparation of albumin—PAA nanocapsules and their controlled release behavior for drugs

New kinds of narrowly distributed protein‐based nanoparticles, bovine serum albumin‐Poly (acrylic acid) (BSA/PAA) nanospheres, and nanocapsules were prepared via in situ polymerization, swelling, and re‐aggregation. The structure and morphology of the nanospheres were characterized by UV‐Vis, FT‐IR, DLS, and TEM. The stability of the BSA/PAA nanospheres and nanocapsules was increased when their skeletons were fixed by cross‐linked agents. The nanospheres carried a positive charge and their size was about 80–110 nm. The protein‐based nanocapsules were stimuli‐responsive with pH value and their hydrodynamic diameter varied from 70 to 230 nm with changes of pH. In vitro release experiments of Rhodamine B and Doxorubicin hydrochloride showed that these biopolymer nanoparticles provided a controlled release of the entrapped drugs for 300 hr. Copyright © 2009 John Wiley & Sons, Ltd.