Stimuli-responsive hybrid composites based on CaCO3 microparticles and smart polyelectrolytes for controllable drug delivery

CaCO₃/aliphatic poly(urethane-amine) (PUA)/sodium polystyrene sulfonate (PSS) hybrid composites with dual-responsive controlled drug delivery property had been prepared via electrostatic interaction. Aliphatic PUA and PSS were employed as smart polyelectrolytes. PSS was also served as crystal growth additive to control the morphology of CaCO₃ microparticles. The electrostatic interaction between PSS and aliphatic PUA under weak-acid condition improved the bonding force between PSS-doped CaCO₃ microparticles and polyelectrolytes. pH-/thermo-responsive drug delivery property and the high drug loading capacity (around 90 %) could be achieved from the prepared hybrid composites. More importantly, the relative content of CaCO₃ microparticles and polyelectrolytes had a significant effect on the morphology and controllable release properties of the hybrid composites. The smart drug release mechanism of the hybrid composites was also analyzed by fitting the cumulative release data to Retger–Peppas equation.     

Dissipative particle dynamic simulation on the assembly and release of siRNA/polymer/gold nanoparticles based polyplex

Dissipative particle dynamics simulation is used to reveal the loading/release of small interfering RNA (siRNA) in pH‐sensitive polymers/gold nanoparticles (AuNPs) polyplex. The conformation dynamics of these polyplex at various Au/siRNA mass ratios, the original AuNPs sizes, polymer types, and pH values are simulated and compared to experimental results. At neutral conditions (pH = 7.4), spherical micelles with a multilayer structure are formed in siRNA/polyethyleneimine/cis‐aconitic anhydride functionalized poly(allylamine)/polyethyleneimine/11‐mercaptoundecanoic acid‐gold nanoparticle (siRNA/PEI/PAH‐Cit/PEI/MUA‐AuNP) polyplex. Large polyplex are obtained with high Au/siRNA mass ratio and/or small original AuNPs size. The release dynamics of siRNA from AuNPs‐polyplex systems were also simulated in the intracellular environment (pH = 5.0). A swelling‐demicellization‐releasing mechanism is followed while the release of siRNA is found much faster for polyplex involving charge‐reversal PAH‐Cit. These findings are qualitatively consistent with the experimental results and may provide valuable guidance in later design and optimization of delivery carriers for siRNA or other molecule probes. © 2017 American Institute of Chemical Engineers AIChE J, 64: 810–821, 2018     

Synthesis and characterization of fast responsive thermo‐ and pH‐sensitive poly[(N,N‐diethylacrylamide)‐co‐(acrylic acid)] hydrogels

BACKGROUND: A considerable amount of research has been focused on smart hydrogels that can respond to external environmental stimuli, especially temperature and pH. In this study, fast responsive thermo‐ and pH‐sensitive poly[(N,N‐diethylacrylamide)‐co‐(acrylic acid)] hydrogels were prepared by free radical copolymerization in aqueous solution using poly(ethylene glycol) (PEG) as a pore‐forming agent. RESULTS: Swelling studies showed that the hydrogels produced had both temperature and pH sensitivity. The deswelling kinetics at high temperature demonstrated that the shrinking rates were influenced by the addition of the pore‐forming agent and the amount of acrylic acid in the initial total monomers. The deswelling curves in low‐buffer solutions had two stages. Pulsatile swelling studies indicated that the PEG‐modified hydrogels were superior to the normal ones. These different swelling properties were further confirmed by the results of scanning electron microscopy. CONCLUSION: Such fast responsive thermo‐ and pH‐sensitive hydrogels are expected to be useful in biomedical fields for stimuli‐responsive drug delivery systems. Copyright © 2008 Society of Chemical Industry     

pH‐sensitive polymeric particles as smart carriers for rebar inhibitors delivery in alkaline condition

The waste problem of the rebar inhibitors is very serious due to that it is a long time before they can exert their best effect in the concrete and they are kept losing all the time. However, there is still no effective solution to alleviate such situation. Meanwhile, drug delivery control technology based on environmental sensitive polymers has been successfully applied in biomedical fields. Thus, poly(acrylic acid)–acrylamide was synthesized as smart carrier for controlling rebar inhibitors delivery in concrete. Dipotassium hydrogen phosphate as model drug was encapsulated inside the polymeric particles via a self‐assembly process. The pH‐responsive activities of the polymeric particles were estimated by monitoring their swelling performances in solutions of different pH values and the drug delivery control characteristics were studied in simulated concrete pore solutions. The results indicate the polymeric particles deserve network structures with high porosity and exhibit excellent pH‐responsive activities, which can perform as perfect intelligent carriers whereas the releasing of the inhibitors follows the first‐order kinetic law. The work suggests a new application field of drug delivery control technology. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45886.     

pH‐responsive core crosslinked polycarbonate micelles via thiol‐acrylate Michael addition reaction

A facile method for the construction of pH‐responsive core crosslinked micelles (CCLMs) based on polycarbonate was developed. Biodegradable amphiphilic block copolymer monomethoxy poly(ethylene glycol)‐b‐Poly(AC) (mPEG‐b‐poly(AC)) with pendant acrylate group was synthesized by means of ring opening polymerization of acryloyl carbonate (AC). Then CCLMs were obtained via thiol‐acrylate Michael addition reaction between the pendant acrylate group in the hydrophobic block and the crosslinker 1,6‐hexanedithiol. DLS results showed that the CCLMs prepared from mPEG‐b‐poly(AC)₂₅ were more stable than uncrosslinked micelles (UCLMs) upon dilution by 10‐fold DMF. Model drug Coumarin 102 was then encapsulated into the micelles. The pH‐responsive release of coumarin 102 from the CCLMs was demonstrated by fluorescence spectroscopy. The core crosslinked polycarbonate micelles have a potential as efficient intracellular smart drug delivery platforms. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44421.     

Dual-responsive release behavior of pH-sensitive PVA/PAAc hydrogels containing temperature-sensitive PVA/PNIPAAm microcapsules

Both temperature and pH responsive drug delivery system was prepared by combining temperature-sensitive poly(vinyl alcohol) (PVA)/poly(N-isopropylacrylamide) (PNIPAAm) microcapsules and pH-sensitive PVA/poly(acrylic acid) (PAAc) hydrogels. The release of drug from the composite hydrogels increased as the pH increased due to the repulsion among the carboxylate anions in the PVA/PAAc hydrogels. The release of drug from the composite hydrogels also increased as the temperature decreased due to the higher hydrophilicity generated below the lower critical solution temperature of PNIPAAm. The compression moduli of composite hydrogels increased with increasing the content of PVA/PNIPAAm microcapsules. The biocompatibility of composite hydrogels was confirmed by the cytotoxicity test.     

Microcapsules prepared from a polycondensate‐based cement dispersant via layer‐by‐layer self‐assembly on melamine‐formaldehyde core templates

Novel microcapsules were prepared from colloidal core–shell particles by acid dissolution of the organic core. Weakly crosslinked, monodisperse and spherical melamine‐formaldehyde polycondensate particles (diameter ～ 1 μm) were synthesized as core template and coated with multilayers of an anionic polyelectrolyte via layer‐by‐layer deposition technique. As polyelectrolytes, an anionic naphthalenesulfonate formaldehyde polycondensate that is a common concrete superplasticizer and thus industrially available, and cationic poly(allylamine hydrochloride) were used. Core removal was achieved by soaking the core–shell particles in aqueous hydrochloric acid at pH 1.6, resulting in hollow microcapsules consisting of the polyelectrolytes. Characterization of the template, the core–shell particles, and the microcapsules plus tracking of the layer‐by‐layer polyelectrolyte deposition was performed by means of zeta potential measurement and scanning electron microscopy. The microcapsules might be useful as microcontainers for cement additives. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Design of intelligent chitosan/heparin hollow microcapsules for drug delivery

In this study, a novel strategy has been developed for the assembly of polyelectrolyte multilayer (PEM) on CaCO₃ templates in acidic pH solutions, where consecutive polyelectrolyte layers (heparin/poly(allylamine hydrochloride) or heparin/chitosan) were deposited on PEM hollow microcapsules established previously on CaCO₃ templates. The PEM build‐up, hollow capsule characterization and successful encapsulation of fluorescein 5(6)‐isothiocyanate (FITC)‐Dextran by coprecipitation with CaCO₃ are demonstrated. Improvement by the removal of CaCO₃ core was achieved while the depositions. In the course of the release profile, high retardation for encapsulated FITC‐Dextran was observed. The combined shell capsules system is a significant trait that has potential use in tailoring functional layer‐by‐layer capsules as intelligent drug delivery vehicles where the preliminary in vitro tests showed the responsiveness on the enzymes. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44425.     

Fabrication of pH‐responsive molecularly imprinted polyethersulfone particles for bisphenol‐A uptake

pH‐responsive molecularly imprinted particles were successfully fabricated by pore‐filling poly (acrylic acid) (PAA) gels into bisphenol‐A (BPA)‐imprinted polyethersulfone particles. The adsorbed BPA amount (or rate) decreased after filling the PAA gels both for the imprinted and nonimprinted particles. However, it was confirmed that changing the acidity of the solution reversibly controls the rebinding ability toward BPA and that the BPA uptake of the pore‐filled particles exhibited chemical valve behavior at a pH between 3 and 6. This finding can be attributed to the swelling of the PAA gels in the particles. The present methodology provides a simple way to prepare pH‐responsive molecularly imprinted materials and is expandable to the imprinting of other hydrophobic molecules, such as dibenzofuran. Also, the results of this work demonstrate the potential of stimuli‐responsive molecularly imprinted polymer materials as smart chemicals and as drug‐delivery systems. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Thermal and pH dual‐responsive hydrogels based on semi‐interpenetrating network of poly(N‐isopropylacrylamide) and collagen nanofibrils

Hydrogels with environment‐sensitive properties have great potential applications in the controlled drug release field. In this paper, hybrid hydrogels with semi‐interpenetrating polymer networks (semi‐IPNs), composed of poly(N‐isopropylacrylamide) (PNIPAM) as the thermo‐sensitive component by in situ polymerization and self‐assembled collagen nanofibrils as the pH‐sensitive framework, were prepared for controlled release of methyl violet as a model drug. From Fourier transform infrared spectroscopy and scanning electron microscopy, it was indicated that the crosslinking of PNIPAM in the presence of collagen nanofibrils led to the formation of semi‐IPNs with homogeneous porous structure, and the semi‐IPNs showed improved thermal stability and elastic properties compared with the native collagen as determined using differential scanning calorimetry and rheologic measurements. Furthermore, the semi‐IPNs possessed swelling behaviors quite different from those of neat collagen or PNIPAM hydrogel under various pH values and temperatures. Correspondingly, as expected, the drug release behavior in vitro for semi‐IPNs performed variously compared with that for single‐component semi‐IPNs, which revealed the tunable performance of semi‐IPNs for release ability. Finally the thermo‐ and pH‐responsive mechanism of the semi‐IPNs was illuminated to provide guidance for the application of the thermo‐ and pH‐sensitive collagen‐based hybrid hydrogels in controlled drug delivery systems. © 2019 Society of Chemical Industry     

Controlled release of bovine serum albumin from stimuli‐sensitive silk sericin based interpenetrating polymer network hydrogels

In recent years, the use of stimuli‐sensitive interpenetrating polymer network (IPN) hydrogels for the encapsulation and controlled release of protein drugs has received significant attention. The purpose of the present study was to investigate the release of bovine serum albumin (BSA), a model drug, from a series of thermosensitive silk sericin (SS) poly(N‐isopropylacrylamide) and pH‐responsive SS poly(methacrylic acid) IPN hydrogels. The effect of the chemical architecture of the IPN was investigated on the percentage loading of BSA and its subsequent release from the loaded devices. The temperature and pH of the release medium were studied for their impact on the release of BSA. The pulsatile releasing behavior of IPN hydrogels revealed that they can be made into microcapsules or thermo‐valves, which act as an on–off release control. © 2013 Society of Chemical Industry     

Hollow,pH‐sensitive calcium–alginate/poly(acrylic acid) hydrogel beads as drug carriers for vancomycin release

In this study, hollow calcium–alginate/poly(acrylic acid) (PAA) hydrogel beads were prepared by UV polymerization for use as drug carriers. The hollow structure of the beads was fortified by the incorporation of PAA. The beads exhibited different swelling ratios when immersed in media at different pH values; this demonstrated that the prepared hydrogel beads were pH sensitive. A small amount (<9%) of vancomycin that had been incorporated into the beads was released in simulated gastric fluid, whereas a large amount (≤67%) was released in a sustained manner in simulated intestinal fluid. The observed drug‐release profiles demonstrated that the prepared hydrogel beads are ideal candidate carriers for vancomycin delivery into the gastrointestinal tract. Furthermore, the biological response of cells to these hydrogel beads indicated that they exhibited good biological safety and may have additional applications in tissue engineering. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

pH responsive polymers with amino acids in the side chains and their potential applications

Design and synthesis of pH responsive polymeric materials has become an important subject in academia as well as in industrial field in recent years due to their applications in diverse field including controlled drug delivery, biomedical applications, membrane science, sensors and actuators, oil recovery, colloid stabilization, etc. Efforts have been made to incorporate stimuli‐responsive biomolecules in synthetic polymers to develop pH responsive “smart” non‐biological hybrid macromolecules with high water solubility, enhanced biocompatibility, bio‐mimetic structure and properties. This review is focused on the recent advances in side‐chain amino acid‐based pH responsive polymers synthesis and potential application aspects of these macromolecular architectures in drug and gene delivery, and other fields. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41084.     

Mussel‐Inspired Hydrogel Composite with Multi‐Stimuli Responsive Behavior

A mussel‐inspired adhesive hydrogel with pH, temperature, and near‐infrared (NIR) light–responsive behavior is designed. The hydrogel system is formulated by combining chitosan modified with catechol motifs, thermo‐responsive poly(N‐isopropylacrylamide) terminated with catechols, and light‐absorbing polypyrrole nanoparticles (PpyNPs). The effects of catechol concentration, molar ratio of Fe³⁺ to catechol units, pH, and the incorporation of the PpyNPs on the mechanical property of the formed hydrogel are investigated. The responsive behaviors of the resulting hydrogel composite to pH, temperature, and NIR light are also demonstrated. The obtained hydrogel also shows promising adhesive property to glass and steel substrates. It is anticipated that the fabricated adhesive hydrogel with multi‐responsive behavior, especially NIR light response, can potentially be useful in a wide range of biomedical applications, such as remotely controlled release systems and removable sealant materials.     

Dual‐stimuli‐responsive polymer‐coated mesoporous silica nanoparticles used for controlled drug delivery

In this article, a temperature‐ and pH‐responsive delivery system based on block‐copolymer‐capped mesoporous silica nanoparticles (MSNs) is presented. A poly[2‐(diethylamino)ethyl methacrylate)] (PDEAEMA)‐b‐poly(N‐isopropyl acrylamide) (PNIPAM) shell on MSNs was obtained through the surface‐initiated atom transfer radical polymerization. The block copolymer PDEAEMA‐b‐PNIPAM showed both temperature‐ and pH‐responsive properties. The release of the loaded model molecules from PDEAEMA‐b‐PNIPAM‐coated MSNs could be controlled by changes in the temperature or pH value of the medium. The as‐desired drug‐delivery carrier may be applied to biological systems in the future. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42395.     

Polythiophene gold nanoparticles composite film for application to glucose sensor

Regioregular poly‐3‐hexylthiophene (regP3HT) and dithiobissuccinimidyl propionate (DTSP) have been used to prepare bifunctionalized gold nanoparticles (Bf AuNPs). Processable properties of regP3HT have been used to obtain regP3HT‐AuNPs‐DTSP film on a gold‐coated glass surface and the succinimidyl group of DTSP in this regP3HT‐AuNPs‐DTSP/Au electrode has been utilized for covalent immobilization of glucose oxidase (GOx). The UV‐visible (UV‐vis), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopic studies have been used to characterize regP3HT‐AuNPs‐DTSP/Au and GOx‐regP3HT‐AuNPs‐DTSP/Au electrode, respectively. This GOx‐regP3HT‐AuNPs‐DTSP/Au bioelectrode shows response time of 10 s, linearity from 25 to 300 mg/dL of glucose and the value of Michaelis‐Menten constant as 5.85 mM (105.3 mg/dL). © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Facile fabrication of double‐walled polymeric hollow spheres with independent temperature and pH dual‐responsiveness for synergetic drug delivery

A dual‐responsive double‐walled polymeric hollow sphere (PHS) serving as a candidate for synergetic drug delivery platform is prepared by a simple and green template polymerization in aqueous medium. The PHS, comprised of thermo‐responsive crosslinked poly(N‐isopropylacrylamide) (PNIPAM) as the inner shell and pH‐responsive crosslinked poly(methacrylic acid) (PMAAc) as the outer shell, is assembled through self‐removal of the thermo‐responsive template from a core‐triple shell structure by free radical polymerization with sequential addition of reactants. The discrete double‐shell structure renders the PHS independent temperature and pH‐controlled swelling/shrinking capability. Taking the advantage of two compartmentalized internal spaces (the core and the interlayer spaces) with independent temperature‐ and pH‐dependent behaviors, two model drugs representing the small molecule and the macromolecule are loaded in selective locations of the PHS. Two drugs show dramatically different release profiles according to environmental temperature and pH, due to the localization of drugs and the stimuli‐dependent property of its protective shells. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44335.     

Construction of magnetic-targeted and NIR irradiation-controlled drug delivery platform with Fe3O4@Au@SiO2 nanospheres

Near-infrared (NIR) light has great potential in biomedical applications due to its advantages of deep penetration depth and low photodamage to biological tissues. In this paper, we constructed a novel core-shell structured drug nanocarrier, Fe₃O₄@Au@SiO₂, for the controlled delivery of etoposide (VP16), a chemotherapeutic drug for cancer patients. The novel core-shell structured drug delivery platform is composed of a mesoporous silica shell and a magnetic Fe₃O₄ core using Au nanoparticles (AuNPs) as the interlayer, which is characterized by atomic force microscopy (AFM), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, N₂ adsorption/desorption isotherms and the magnetic measurements with vibrating-sample magnetometer (VSM). The synergistic effects of AuNPs, mesoporous silica and Fe₃O₄ make the core-shell structured nanocomposites an excellent candidate for targeted and NIR light irradiation-controlled drug delivery. For the proposed nanocarrier of VP16, the mesopores in silica can enhance the encapsulation capacity of the nanocarrier and the AuNPs can effectively convert the NIR light into heat to speed up the drug deliver; meanwhile, the incorporation of Fe₃O₄ with high magnetization to the drug delivery platform realize drug targeting under an applied external magnetic field.     

Temperature,pH, and reduction triple‐stimuli‐responsive inner‐layer crosslinked micelles as nanocarriers for controlled release

Temperature, pH, and reduction triple‐stimuli‐responsive inner‐layer crosslinked micelles as nanocarriers for drug delivery and release are designed. The well‐defined tetrablock copolymer poly(polyethylene glycol methacrylate)–poly[2‐(dimethylamino) ethyl methacrylate]–poly(N‐isopropylacrylamide)–poly(methylacrylic acid) (PPEGMA‐PDMAEMA‐PNIPAM‐PMAA) is synthesized via atom transfer radical polymerization, click chemistry, and esterolysis reaction. The tetrablock copolymer self‐assembles into noncrosslinked micelles in acidic aqueous solution. The core‐crosslinked micelles, shell‐crosslinked micelles, and shell–core dilayer‐crosslinked micelles are prepared via quaternization reaction or carbodiimide chemistry reaction. The crosslinked micelles are used as drug carriers to load doxorubicin (DOX), and the drug encapsulation efficiency with 20% feed ratio reached 59.2%, 73.1%, and 86.1%, respectively. The cumulative release rate of DOX is accelerated by single or combined stimulations. The MTT (3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay verifies that the inner‐layer crosslinked micelles show excellent cytocompatibility, and DOX‐loaded micelles exhibit significantly higher inhibition for HepG2 cell proliferation. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46714.