Temperature/pH/magnetic triple‐sensitive nanogel–hydrogel nanocomposite for release of anticancer drug

Hydrogels, nanogels and nanocomposites show increasing potential for application in drug delivery systems due to their good chemical and physical properties. Therefore, we were encouraged to combine them to produce a new compound with unique properties for a long‐term drug release system. In this regard, the design and application of a nanocomposite hydrogel containing entrapped nanogel for drug delivery are demonstrated. To this aim, we first prepared an iron oxide nanocomposite nanogel based on poly(N‐isopropylacrylamide)‐co‐((2‐dimethylaminoethyl) methacrylate) (PNIPAM‐co‐PDMA) grafted onto sodium alginate (NaAlg) as a biocompatible polymer and iron oxide nanoparticles (ION) as nanometric base (PND/ION‐NG). This was then added into a solution of PDMA grafted onto NaAlg. Through dropwise addition of mixed aqueous solution of iron salts into the prepared polymeric solution, a novel hydrogel nanocomposite with excellent pH, thermal and magnetic responsivity was fabricated. The synthesized samples were fully characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy with energy‐dispersive X‐ray analysis, vibrating sample magnetometry and atomic force microscopy. A mechanism for the formation of PNIPAM‐co‐PDMA/NaAlg‐ION nanogel–PDMA/NaAlg‐ION hydrogel and PND/ION nanogel is suggested. Swelling capacity was measured at various temperatures (25 to 45 °C), pH values (from 2 to 11) and magnetic field and under load (0.3 psi) and the dependence of swelling properties of the nanogel–hydrogel nanocomposite on these factors was well demonstrated. The release rate of doxorubicin hydrochloride (DOX) as an anticancer drug was studied at different pH values and temperatures in the presence and absence of a magnetic field. The results showed that these factors have a high impact on drug release from this nanocomposite. The result showed that DOX release could be sustained for up to 12.5 days from these nanocomposite hydrogels, significantly longer than that achievable using the constituent hydrogel or nanogel alone (<1 day). The results indicated that the nanogel–hydrogel nanocomposite can serve as a novel nanocarrier for anticancer drug delivery. © 2019 Society of Chemical Industry     

Dual‐Crosslinked Human Serum Albumin‐Polymer Hydrogels for Affinity‐Based Drug Delivery

A dual‐crosslinked in situ gelling drug delivery scaffold based on dextran (DEX), thiolated serum albumin, and poly(ethylene glycol) (PEG) is presented. Dextran–vinyl sulfone conjugates with varied molecular weight and degrees of substitution are synthesized by controlling the reaction time and temperature with divinyl sulfone. Dextran–human serum albumin (sHSA) hydrogels are prepared using a thiol‐vinyl sulfone Michael addition reaction with thiolated albumin as the crosslinker. Poly(ethylene glycol) dithiol is added as a third component to the crosslinked dextran–human serum albumin hydrogel to facilitate additional crosslinking, and reduce gelation time, while modulating the physicochemical properties of the Dex–sHSA–PEG network. The onset of gelation of the modular three‐component dual‐crosslinked hydrogel network ranges from 45 min to 1.5 h depending on gel constituent concentrations and the gelation temperature (25 or 37 °C). All gels remain stable for over a 25 d period under physiological conditions. In vitro drug release assays show that dual‐crosslinked Dex–sHSA–PEG hydrogels can deliver doxorubicin in a sustained manner over 7 d. Finally, a Tetrazolium‐based assay shows the biocompatible nature of the Dex–sHSA–PEG hydrogels and capacity to deliver doxorubicin successfully to MCF‐7 breast cancer cells.     

Novel thermosensitive hydrogel composites based on poly(d,l‐lactide‐co‐glycolide) nanoparticles embedded in poly(n‐isopropyl acrylamide) with sustained drug‐release behavior

To reach sustained drug release, a new composite drug‐delivery system consisting of poly(d,l ‐lactide‐co‐glycolide) (PLGA) nanoparticles (NPs) embedded in thermosensitive poly(N‐isopropyl acrylamide) (PNIPAAm) hydrogels was developed. The PNIPAAm hydrogels were synthesized by free‐radical polymerization and were crosslinked with poly(ethylene glycol) diacrylate, and the PLGA NPs were prepared by a water‐in‐oil‐in‐water double‐emulsion solvent‐evaporation method. The release behavior of the composite hydrogels loaded with albumin–fluorescein isothiocyanate conjugate was studied and compared with that of the drug‐loaded neat hydrogel and PLGA NPs. The results indicate that we could best control the release rate of the drug by loading it to the PLGA NPs and then embedding the whole system in the PNIPAAm hydrogels. The developed composite hydrogel systems showed near zero‐order drug‐release kinetics along with a reduction or omission of initial burst release. The differential scanning calorimetry results reveal that the lower critical solution temperature of the developed composite systems remained almost unchanged (<1°C increase only). Such a characteristic indicated that the thermosensitivity of the PNIPAAm hydrogel was not distinctively affected by the addition of PLGA NPs. In conclusion, an approach was demonstrated for the successful preparation of a new hybrid hydrogel system having improved drug‐release behavior with retained thermosensitivity. The developed systems have enormous potential for many biotechnological applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40625.     

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     

Dual pH‐ and temperature‐responsive hydrogels with extraordinary swelling/deswelling behavior and enhanced mechanical performances

pH‐ and temperature‐responsive semi‐interpenetrating nanocomposite hydrogels (NC hydrogels) were prepared with surface‐functionalized graphene oxide (GO) as the crosslinker, N‐isopropylacrylamide (NIPAM) as the monomer, and chitosan (CS) as an additive. The effects of 3‐(trimethoxysilyl)propylmethacrylate‐modified GO sheets and CS content on various physical properties were investigated. Results show that PNIPAM/CS/GO hydrogels undergo a large volumetric change in response to temperature. Swelling ratios of PNIPAM/CS/GO hydrogels are much larger than those of the conventional organically crosslinked PNIPAM hydrogels. The deswelling test indicates that the deswelling rate was greatly enhanced by incorporating CS into the hydrogel network and using the surface‐functionalized GO as the crosslinker. The pH‐sensitivity of PNIPAM/CS/GO hydrogels is evident below their volume phase transition temperature. Moreover, the PNIPAM/CS/GO hydrogels have a much better mechanical property compared with traditional hydrogels even in a high water content of 90%. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41530.     

Fast near infrared light response hydrogel as medical dressing for wound healing

Fast-response smart hydrogels with combination of appropriate mechanical strength, self-healing and tissue adhesiveness ability, and controllable drug release performance are highly desired as wound dressing practice. Herein, a novel dual-crosslinking hydrogel with gold nanorods (AuNRs) well dispersed in its polymer network, D-hydrogel@AuNR, was constructed via ultraviolet light initiated radical copolymerization of acrylamide (AM), isopropylacrylamide (NIPAAM), and dopamine methacrylamide (DMA) in a complex solution of AuNRs and cysteamine-grafted oxidized sodium alginate (OSA-SH). The produced D-hydrogel@AuNR exhibits fast response to the near infrared light (NIR, 808 nm) exposure and a cumulative release level of encapsulated gentamicin sulfate (GS) up to 75% within 60 s laser irradiation. The dual-crosslinking network that the first MBA crosslinked P(AM-co-NIPAAM-co-DMA) network and the second imine bonded network makes the tensile stress and tensile strain of D-hydrogel@AuNR could reach up to 397.0 k Pa and 240%, respectively. Moreover, the received D-hydrogel@AuNR also exhibits remarkable self-healing ability and excellent cell affinity and tissue adhesiveness. These desirable properties of D-hydrogel@AuNR together make it an appropriate candidate for practical wound dressing under different biomedical conditions.     

pH‐responsive hydrogels with dispersed hydrophobic nanoparticles for the delivery of hydrophobic therapeutic agents

To investigate the delivery of hydrophobic therapeutic agents, a new class of polymer carriers was synthesized. These carriers are composed of two components: (i) a pH‐responsive hydrogel composed of methacrylic acid grafted with poly(ethylene glycol) tethers, P(MAA‐g‐EG), and (ii) hydrophobic poly(methyl methacrylate) (PMMA) nanoparticles. Before the P(MAA‐g‐EG) hydrogel was crosslinked, PMMA nanoparticles were added to the solution and upon exposure to UV light they were photoencapsulated throughout the P(MAA‐g‐EG) hydrogel structure. The pH‐responsive behavior of P(MAA‐g‐EG) is capable of triggered release of a loaded therapeutic agent, such as a low molecular weight drug or protein, when it passes from the stomach (low pH) to upper small intestine (neutral pH). The introduction of PMMA nanoparticles into the hydrogel structure affected the swelling behavior, therapeutic agent loading efficiency, and solute release profiles. In equilibrium swelling conditions the swelling ratio of nanoparticle‐containing hydrogels decreased with increasing nanoparticle content. Loading efficiencies of the model therapeutic agent fluorescein ranged from 38% to 51% and increased with increasing hydrophobic content. Release studies from neat P(MAA‐g‐EG) and the ensuing P(MAA‐g‐EG) hydrogels containing nanoparticles indicated that the transition from low pH (2.0) to neutral pH (7.0) triggered fluorescein release. Maximum fluorescein release depended on the structure and hydrophobicity of the carriers used in these studies. Copyright © 2012 Society of Chemical Industry     

Imaging‐Guided pHe and Glutathione Dual Responsive Polypeptide Nanogel for Smart Drug Delivery

A negatively charged polypeptide nanogel, near‐infrared (NIR) cyanine dye (Cy5.5) conjugated and 2,3‐dimethylmaleic anhydride (DMA) modified poly‐l ‐lysine‐co‐l ‐cystine (CDPLC), is synthesized and is used as an imaging‐guided sequential drug delivery system. The CDPLC nanogel can respond to two general stimulations in sequence: extracellular tumor acidic microenvironment pHe (6.8–6.5) and intracellular high concentration glutathione (GSH). Under pHe, the DMA shell of the nanogel is removed and a charge reversal takes place, resulting in positively charged nanogel which can be internalized by cancer cells easily. Once internalized into tumor cells, the increased intracellular GSH concentration further promotes DOX release from the nanogel and DOX is enriched to the nucleus. Cy5.5 is conjugated to the nanogel as an NIR fluorescent probe, making it possible for imaging‐guided drug delivery, which is confirmed by the MTT and confocal laser scanning microscopy via in vitro experiments. The as‐prepared nanogel is a potential theranostic for cancer therapy.     

Study of pH/temperature dual stimuli‐responsive nanogels with interpenetrating polymer network structure

Nanogels with interpenetrating polymer network (IPN) structure based on poly(N‐isopropylacrylamide) (PNIPAM) and poly(acrylic acid) (PAA) were synthesized by in situ polymerization of acrylic acid and N, N′‐methylenebisacrylamide within the PNIPAM nanogels. Their IPN structure was confirmed using transmission electron microscopy after staining by uranyl acetate. The temperature‐ or pH‐dependent hydrodynamic diameters measured using dynamic laser light scattering show that the IPN nanogels have pH and temperature dual stimuli‐responsive properties. As compared to previously reported pH/temperature dual stimuli‐responsive nanogels, these IPN nanogels have the advantage of less mutual interference between the temperature‐responsive and pH‐responsive components, which is beneficial for their applications in controlled drug release and sensors. The temperature‐ and pH‐triggered volume phase transition mechanisms of the IPN nanogels were tested by probing the microenvironment change of their PNIPAM and PAA chains upon phase transition using infrared (IR) absorption spectra measured at different pH values and IR difference spectra obtained by subtracting the IR spectrum obtained before temperature‐induced phase transition from that obtained after phase transition. Copyright © 2012 Society of Chemical Industry     

Spray‐dried microparticles composed of cinnamoyl poly(N‐isopropylacrylamide‐co‐hydroxyethylacrylate) and gold nanoparticle

Temperature‐ and NIR irradiation‐responsive microparticles composed of cinnamoyl poly(N‐isopropylacrylamide‐co‐hydroxyethylacrylate) [CinP(NIPAM‐HEA)] and gold nanoparticle (GNP) were prepared by a spray‐drying method. According to the cloud points determined by an optical method, the HEA content in P(NIPAM‐HEA) had no marked effect on the lower critical solution temperature (LCST). However, the cinnamoyl group content in CinP(NIPAM‐HEA) had a significant effect on the LCST. The LCSTs determined by a calorimetric method was in agreement with those determined by an optical method. The hydrodynamic mean diameter of gold nanoparticle (GNP) prepared by reducing gold ions was about 30 nm and it seemed to be a nanosphere on TEM photo. Spray‐dried CinP(NIPAM‐HEA) microparticles containing GNP was 1.5 μm to 12 μm in diameter on SEM photo. Gold was detected on the energy‐dispersive X‐ray spectrum of the microparticles. The amount of FITC‐dextran released for 12 h from the microparticles was much higher at temperatures above the LCST (at 37 °C and 45 °C) than below the LCST (at 20 °C and 25 °C). The cumulative release amount in 12 h was only about 3% without NIR irradiation, whereas the value was about 26.5% when NIR was irradiated to the microparticle suspension. The photothermal energy generated by GNP was believed to render the thermosensitive copolymers de‐swollen and hydrophobic, allowing for the active release of dye from the microparticles. The NIR irradiation‐responsive GNP‐loaded microparticles could be applied to the development of NIR‐responsive drug carriers which release their contents in response to an external stimulus (i.e., NIR irradiation). © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44141.     

Swelling behaviour and paracetamol release from poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide-itaconic acid) hydrogels

Copolymer hydrogels of N-isopropylacrylamide and itaconic acid (IA), crosslinked with N,N′-methylenebisacrylamide, were prepared by radical copolymerization. These hydrogels were investigated with regard to their composition to find materials with satisfactory swelling and drug release properties. A paracetamol is used as a model drug to investigate drug release profile of the hydrogels. It was found that the investigated hydrogels exhibited pH- and temperature-dependent swelling behaviour with restricted swelling and lower equilibrium degree of swelling at lower pH values and temperatures above the LCST value of PNIPAM (around 34 °C). The diffusion exponent for paracetamol release indicate that the mechanism of paracetamol release are governed by Fickian diffusion, while in all release media initial diffusion coefficient was lower than late time diffusion coefficient. Furthermore, the paracetamol release rate depends on the hydrogel degree of swelling and it increased in the first stage of diffusion process, whereas was no significant difference thereafter. The presence of the IA moieties incorporated into the network weakened the shear resistance of the hydrogels. In order to calculate the pore size the characteristic ratio for PNIPAM, C _n  = 11.7, was calculated. Based on the pore size, the investigated hydrogels can be regarded as microporous. According to the obtained results swelling behaviour, mechanical properties, drug-loading capacity and the drug release rate could be controlled by hydrogel composition and crosslinking density, which is important for application of the investigated hydrogels as drug delivery systems.     

Synthesis of polyhedral oligomeric silsesquioxane nano‐crosslinked poly(ethylene glycol)‐based hybrid hydrogels for drug delivery and antibacterial activity

The synthesis is reported of novel hybrid hydrogels based on ethylenediaminetetraacetic acid dianhydride and poly(ethylene glycol) (PEG) with octa‐aminopropyl polyhedral oligomeric silsesquioxane hydrochloride salt (OA‐POSS) as a nano‐crosslinker under solvent‐free conditions. The molecular weight of PEG was varied between 600 and 1000 Da. The synthesized hydrogels were characterized using various techniques. Further, the swelling behavior and antibacterial activity of the hydrogels and release kinetics of metronidazole (MTZ) as a model drug from them were evaluated. Experimental results demonstrate that hydrogels with tunable properties can be synthesized by varying the PEG molecular weight and type of crosslinker (hybrid or organic). Among the synthesized hybrid hydrogels, that crosslinked by OA‐POSS with long PEG chains (1000 Da) showed the highest swelling degree (2000%), drug encapsulation efficiency (88%) and extent of MTZ release (96%). © 2018 Society of Chemical Industry     

Synthesis and characterization of NIR-responsive Aurod@pNIPAAm-PEGMA nanogels as vehicles for delivery of photodynamic therapy agents

A near-infrared (NIR)-responsive Au_rod@pNIPAAm-PEGMA nanogel was synthesized in two steps, growing a PEGMA monolayer on the surface of gold nanorods (AuNRs), followed by in situ polymerization and cross-linking of N-iso-propylacrylamide (NIPAAm) and poly-(ethylene glycol)-methacrylate (PEGMA). The AuNRs and Au_rod@pNIPAAm-PEGMA nanogel were characterized by UV–vis spectroscopy, Raman spectroscopy, Fourier transform infrared spectroscopy, and transmission electron microscopy, respectively. The lower critical solution temperature of the Au_rod@pNIPAAm-PEGMA nanogel could be tuned by changing the molar ratio of NIPAAm/PEGMA. The NIR-mediated drug release behavior of the Au_rod@pNIPAAm-PEGMA nanogel was studied with zinc phthalocyanines (ZnPc₄) as a drug model. It was also demonstrated that the loaded ZnPc₄ could keep the capability of generating singlet oxygen, and the in vitro study showed a great photodynamic therapy (PDT) effect on Hela cells. It thus indicated the potential of this Au_rod@pNIPAAm-PEGMA nanogel for application as a drug carrier in PDT, which might make contributions to oncotherapy.     

Fast responsive poly(acrylic acid‐co‐N‐isopropyl acrylamide) hydrogels based on new crosslinker

Novel dual temperature‐ and pH‐sensitive poly(acrylic acid‐co‐N‐isopropylacrylamide), AA/NIPAAm, hydrogels were successfully prepared by chemical crosslinking with crosslinkers. Copolymers of AA/NIPAAm were crosslinked in the presence of different mol % of N,N‐methylene bisacrylamide (MBA) and melamine triacrylamide (MAAm) as crosslinkers by bulk radical polymerization. The resultant xerogels were characterized by extracting the soluble fractions and measuring the equilibrium water content. Lower critical solution transition temperatures (LCST) were measured by DSC. The properties of crosslinked AA/NIPAAm series are evaluated in terms of compositional drift of polymerization, heterogeneous crosslinking, and chemical structure of the relevant components. Soluble fractions of the crosslinked networks were reduced by varying the MAAm and MBA concentrations. The influence of environmental conditions such as temperature and pH on the swelling behavior of these polymeric gels was investigated. The swelling behaviors of the resulting gels show pH sensitivity. The prepared MAAm type AA/NIPAAm hydrogels exhibited a more rapid deswelling rate than MBA type AA/NIPAAm hydrogels in ultra pure water in response to abrupt changes from 20°C to 50°C. The results of this study provide valuable information regarding the development of dual stimuli‐sensitive hydrogels with fast responsiveness. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation and property of starch nanoparticles reinforced aldehyde–hydrazide covalently crosslinked PNIPAM hydrogels

Injectable, de‐crosslinkable, and thermosensitive hydrogels are obtained by hydrazide‐functionalized poly(N‐isopropylacrylamide) and aldehyde‐functionalized dextrin through in situ crosslinked method. Natural based and degradable starch nanoparticles (SNPs) are used as fillers in order to improve mechanical property of hydrogels. Internal morphology, dynamic modulus, thermosensitivity property, de‐crosslinking performance, drug release, and in vitro cytotoxicity of hydrogels are investigated. Results show that SNPs disperse well throughout hydrogel and have no significant influence on gelation time and de‐crosslinking performance. Elasticity property of composite hydrogel prepared from 9.0 wt % precursors with 1.5 wt % fillers is improved significantly by SNPs and maximum storage modulus reaches 399.2 kPa, but 89.6 kPa of unreinforced hydrogels. Hydrogels exhibit good thermosensitive performance at alternating cyclic temperature of 25 and 37 °C. Doxorubicin hydrochloride‐loaded hydrogels can release more than 25 days. No significant cytotoxicity to L929 fibroblast cells is observed through a CCK‐8 assay for hydrogels, precursors, and SNPs. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45761.     

Injectable thermosensitive hydrogels for intra‐articular delivery of methotrexate

Intra‐articular drug delivery is the preferred approach for targeting pharmacologic treatment directly at the joints to reduce undesirable side effects associated with systemic drug delivery. In this study, a controlled delivery system of methotrexate (MTX) based on injectable thermosensitive poly(ε‐caprolactone)‐poly(ethylene glycol)‐poly(ε‐caprolactone) (PCL‐PEG‐PCL, PEP) hydrogels was developed for the intra‐articular drug delivery. The thermosensitive PEP copolymers were prepared by ring‐opening polymerization. The synthesized PEP copolymers were characterized for their structure, composition, and the sol‐to‐gel transition. The in vitro MTX release from the PEP hydrogels was studied. MTX plasma concentration following intra‐articular injection into healthy rats was determined by HPLC. Biocompatibility was confirmed by histology analysis after the intra‐articular injection. The synthesized PEP copolymers aqueous solutions formed in situ gel rapidly after the injection. PEP hydrogels showed the ability to control the release of incorporated MTX. Following intra‐articular injection, the PEP hydrogels decreased the clearance rate of MTX in the joint cavity. The maximum plasma concentrations of MTX in rats injected with free MTX were threefold higher than that of the groups injected with MTX hydrogels. These results suggest that the intra‐articular delivery of the PEP hydrogels may be a viable strategy for the controlled release of drugs for treating arthritis diseases. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Smart carboxymethylchitosan hydrogels that have thermo‐ and pH‐responsive properties

Thermo‐responsive poly(N‐isopropylacrylamide) (poly(NIPAAm)) and pH‐responsive poly(N,N′‐diethylaminoethyl methacrylate) (poly(DEAEMA)) polymers were grafted to carboxymethylchitosan (CMC) via radical polymerization to form highly water swellable hydrogels with dual responsive properties. Ratios of CMC, NIPAAm to DEAEMA used in the reactions were finely adjusted such that the thermo and pH responsiveness of the hydrogels was retained. Scanning electron microscopy (SEM) indicated the formation of an internal porous structure for the swollen CMC hydrogels upon incorporation of poly(NIPAAm) and poly(DEAEMA). Effect of temperature and pH changes on water swelling properties of the hydrogels was investigated. It was found that the water swelling of the hydrogels was enhanced when the solution pH was under basic conditions (pH 11) or the temperature was below its lower critical solution temperature (LCST). These responsive properties can be used to regulate releasing rate of an entrapped drug from the hydrogels, a model drug, indomethacin was used to demonstrate the release. These smart and nontoxic CMC‐based hydrogels show great potential for use in controlled drug release applications with controllable on‐off switch properties. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41505.     

Design of a drug delivery system based on poly(acrylamide‐co‐acrylic acid)/chitosan nanostructured hydrogels

To obtain biodegradable materials for biomedical applications, new biopolymeric hydrogels based on blends of polyacrylamide nanoparticles and chitosan have been prepared. In this work, we have studied the behavior of the diffusion of ascorbic acid (V‐C) from poly(acrylamide‐co‐acrylic acid)/chitosan nanostructured hydrogels. The process involves the synthesis of nanoparticles of polyacrylamide by inverse microemulsion polymerization and their complexation with chitosan dissolved in an acrylic acid aqueous solution. We have studied the effect of the concentration of the polyacrylamide nanoparticles, which are crosslinked with N,N′‐methylenebisacrylamide, in the delivery of V‐C. The results indicate that the drug delivery operates by a non‐Fickian mechanism. Also, we have obtained the diffusion coefficient for V‐C in gels for different nanoparticle concentrations, using a modified form of Fick's second law that takes into account dimensional changes in the hydrogels during drug release. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Microwave‐assisted preparation of temperature sensitive poly(N‐isopropylacrylamide) hydrogels in poly(ethylene oxide)‐600

In this article, a series of poly(N‐isopropylacrylamide) (PNIPAM)‐based hydrogels were prepared under microwave irradiation using poly(ethylene oxide)‐600 (PEO‐600) as reaction medium and microwave‐absorbing agent as well as pore‐forming agent. All of the temperature measurements, gel fractions, and FTIR analyses proved that the PNIPAM hydrogels were successfully synthesized. Within 1 min, the PNIPAM hydrogel with a 98% yield was obtained under microwave irradiation. The PNIPAM hydrogels thus prepared exhibited controllable properties such as pore size, equilibrium swelling ratios, and swelling/deswelling rates when changing the feed weight ratios of monomer (N‐isopropylacrylamide, NIPAM) to PEO‐600. These properties are well adapted to the different requirements for their potential application in many fields such as biomedicine. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102:4177–4184, 2006     

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.