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1.
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  相似文献   

2.
Polypseudorotaxane (PPR) hydrogels formed by inclusion complexes between poly(ethylene glycol) (PEG) and α-cyclodextrin (α-CD) are highlighted as promising biomaterial for drug delivery. Here, we report a novel injectable PPR hydrogel containing graphene oxide (GO) for pH-responsive controlled release of doxorubicin hydrochloride (DOX). Our results showed that the gelation rates of the PEG/α-CD supramolecular structures could be tailored depending on the reagent concentrations. The formation of PEG/α-CD inclusion complexes was confirmed by TEM and XRD, the latter further confirming that GO restricts their formation. The supramolecular hydrogels were easily loaded with DOX by simple addition into the PEG solution before the complex formation with the α-CD solution. Noteworthy, disruption of ionic interactions between DOX and GO in the nanocomposite at pH = 5.5 resulted in higher DOX release than under physiological conditions (pH = 7.4). This pH dependence was barely observed in pure PPR hydrogel. These findings introduce DOX-loaded supramolecular hydrogels nanocomposites as promising carriers for pH-responsive and therefore localized, drug delivery systems.  相似文献   

3.
Poly(2‐ethyl‐2‐oxazoline) and acrylic acid were copolymerized in different compositions using γ‐rays‐induced polymerization and cross‐linking to obtain a series of pH‐sensitive hydrogels. The preparation parameters that may affect the copolymerization process such as the feed solution composition and irradiation dose were optimized. Swelling characteristics of the obtained polymeric hydrogels were evaluated. The results show the significant effects of the hydrogel composition, soaking time, and pH on the swelling equilibrium. The diffusion parameters obtained at pH 1 and 7 show the possibility of using the prepared hydrogels in the field of colon‐specific drug delivery systems. Ibuprofen as a model drug was loaded into (poly(2‐ethyl‐2‐oxazoline)/acrylic acid) copolymer hydrogel to investigate their drug release behavior at different pH values. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011  相似文献   

4.
The amphiphilic block copolymer poly(methacrylic acid-co-2-nitroimidazole acrylate)-b-poly(2-(N,N-dimethylamino)ethyl methacrylate) (P(MAA-co-NIMA)-b-PDMAEMA) with the hypoxia/temperature/pH triple responsiveness is synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT), hydrolysis, and 3-(3-dimethylaminopropyl)-1-ethylcarbodiimide (EDC) reactions, and successfully self-assembled into micelles. The hypoxia response in vitro is realized, and then the sensitivity of the self-assembled micelles to the hypoxia condition is studied by controlling the grafting amount of aminated 2-nitroimidazole. Because 2-(N,N-dimethylamino) ethyl methacrylate (DMAEMA) is a typical material sensitive to temperature and pH conditions, the self-assembled micelles are also responsive to temperature and different acidic/basic conditions. In addition, the cumulative release rate of doxorubicin (DOX) at 42 °C, pH = 6.0, and hypoxic conditions increases significantly, and verifies the synergistic promotion effect of the above stimulations. This intelligent polymer with triple response mechanism improves the controllability and efficiency of drug release, and is expected to be a drug carrier for cancer treatment.  相似文献   

5.
This article deals with the synthesis of hybrid nanocomposite hydrogels through the combination of cellulose (C), polypropylene oxide/poly ethylene oxide (PPO/PEO), and silver nanoparticles (AgNPs) by in situ polymerization technique for the in vitro release of ornidazole drugs. The structure of the resulted materials is identified using SEM, XRD, FTIR, XPS, and TGA spectroscopic techniques. The resulting structure, morphology, thermo responsive property, water retention, and swelling behavior of hydrogels are investigated. The rheological measurement is studied to establish the enhancement of the viscoelasticity and stiffness of hydrogels. The antibacterial activity of the biodegradable silver hybrid nanocomposite hydrogel is investigated by inhibition zone method against gram positive and negative bacteria. Maximum drug release of 96.4% is recorded at 7.4 pH in 5 h. The biocompatibility and cytotoxicity of the hybrid nanocomposite hydrogel are verified using mouse fibroblast cell line L-929 (ATCC CCL-1) cells for their possible use as controlled drug delivery vehicles. The nontoxic nature makes the materials more biocompatible and suitable to apply in the biological systems. Therefore, nontoxic and biocompatible natures of present materials with improved thermal and rheological properties support for their possible uses as drug delivery vehicles.  相似文献   

6.
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.  相似文献   

7.
8.
Over the last decade, nanocomposite hydrogels have been provided a new approach for the biomedical field. In this work, a novel pH-responsive nanocomposite hydrogel was fabricated using simultaneous in situ formation of magnetite iron oxide nanoparticles and hydrogel networks of poly(acrylic acid) grafted onto chitosan. The effects of various types of precursor molecules, pH, salt, and loading pressure were examined on the swelling properties of resulting nanocomposite hydrogels. The synthesized nanocomposite hydrogel was well characterized using different instruments. In vitro drug releasing behavior of doxorubicin was studied at pH 5.4 and 7.4. The drug release mechanism was investigated through different kinetic models. These experimental results open a new opportunity to make pH-responsive nanocomposite hydrogel devices for controlled delivery of drug.  相似文献   

9.
In the present work, a nanocomposite hydrogel is designed consisting of gum acacia, poly(acrylamide) and carbon nitride by facile microwave approach. This nanocomposite hydrogel is sensitive to environmental stimuli which is essential for its application in environmental remediation and as a drug delivery system. The effects of carbon nitride percentage and microwave Watt variation on swelling capacity of gum acacia‐cl‐poly(acrylamide)@carbon nitride (Ga‐cl‐PAM@C3N4) nanocomposite hydrogel are analyzed. The structural characterizations are considered by numerous techniques such as FTIR (Fourier transform infra‐red spectroscopy), X‐ray diffraction, transmission electron microscopy, scanning electron microscopy, and elemental mapping. Batch experiment is performed for remediation of ciprofloxacin (CIP) drug from water. Various parameters such as effect of ciprofloxacin doses, Ga‐cl‐PAM@C3N4 nanocomposite hydrogel dosage, pH, time and temperature for adsorption of CIP on gum acacia‐cl‐poly(acrylamide)@carbon nitride nanocomposite hydrogel is examined. Maximum adsorption capacity of Ga‐cl‐PAM@C3N4 nanocomposite hydrogel observed is 169.49 mg g?1 at pH 6.4. The drug loading and drug release capacity of Ga‐cl‐PAM@C3N4 nanocomposite hydrogel is investigated for ciprofloxacin. Drug release is monitored in artificial ocular solution (pH 8), saline (pH 5.5), acetate buffer (pH 2.2), and distilled water. Maximum drug release is observed in artificial ocular solution.  相似文献   

10.
Self‐healable hydrogels are promising soft materials with great potential in biomedical applications due to their autonomous self‐repairing capability. Although many attempts are made to develop new hydrogels with good self‐healing performance, to integrate this characteristic along with other responsive multifunctions into one hydrogel still remains difficult. Here, a self‐healable hybrid supramolecular hydrogel (HSH) with tunable bioadhesive and stimuli‐responsive properties is reported. The strategy is imparting graphene oxide (GO) nanosheets and quadruple hydrogen bonding ureido‐pyrimidinone (UPy) moieties into a thermoresponsive poly(N‐isopropylacrylamide) (PNIPAM) polymer matrix. The obtained GO–HSH hydrogel shows rapid self‐healing behavior and good adhesion to various surfaces from synthetic materials to biological tissue. In addition, doxorubicin hydrochloride (DOX) release profiles reveal the dual thermo‐ and pH‐responsiveness of the GO–HSH hydrogel. The DOX‐loaded hydrogel can further directly adhere to titanium substrate, and the released DOX from this thin hydrogel coating remains biologically active and has high capability to kill tumor cells.  相似文献   

11.
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  相似文献   

12.
pH‐Responsive amphiphilic branched copolymers were prepared from poly(ethylene glycol) methyl ether methacrylate (PEGMA), 2‐(diethylamino)ethyl methacrylate (DEAEMA), 2‐(tert‐butylamino)ethyl methacrylate (tBAEMA), and ethylene glycol dimethacrylate (EGDMA) utilizing a thiol‐modified free radical polymerization. The molecular structures of copolymers were confirmed by proton nuclear magnetic resonance spectroscopy (1H NMR) and triple‐detection gel permeation chromatography (tri‐GPC). The aqueous solution behaviors of the obtained copolymers were investigated by dynamic light scattering (DLS). The DLS data showed that about 16 nm polymer particles comprising of hydrophobic poly(tert‐butylamino)ethyl methacrylate (PtBAEMA) and poly(diethylaminoethyl methacrylate (PDEAEMA) core, hydrophilic PEGMA corona were formed above pH 8. With the decrease of pH from 8 to 6, a dramatic increase in the hydrodynamic radius of polymer particles from 16 nm to 130 nm was observed resulting from the protonation of the PDEAEMA segment. Moreover, in vitro drug release behaviors of the resulting polymer assemblies at different pH values were also investigated to evaluate their potential as sustained release drug carriers. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42183.  相似文献   

13.
Jie Zhang 《Polymer》2009,50(11):2516-198
Dual temperature- and pH-sensitive comb-type grafted cationic hydrogels are successfully synthesized by grafting polymeric chains with freely mobile ends, which are composed of both N-isopropylacrylamide (NIPAM) segments and N,N-dimethylamino ethyl methacrylate (DMAEMA) segments, onto the backbone of crosslinked poly(NIPAM-co-DMAEMA) networks. Equilibrium and dynamic swelling/deswelling properties of the prepared hydrogels responding to pH and/or temperature are investigated. The prepared hydrogels demonstrate a lower critical solution temperature (LCST) at about 34 °C and a pKa value at about pH 7.3. At lower pH and lower temperature, both the swelling degree and the swelling rate of the comb-type grafted hydrogel are larger than those of the normal-type crosslinked hydrogel. The comb-type grafted poly(NIPAM-co-DMAEMA) hydrogel exhibits a more rapid deswelling rate than that of the normal-type hydrogel in response to a pH jump from 2.0 to 11.0 at a fixed temperature. The volume changes of the poly(NIPAM-co-DMAEMA) hydrogels are acute in a series of fixed buffer solutions with an abrupt increase of environmental temperature from 18 °C to a temperature higher than the LCST. The comb-type grafted poly(NIPAM-co-DMAEMA) hydrogels show quite fast shrinking behaviors in response to simultaneous dual temperature and pH stimuli. Drug-release in vitro from the prepared poly(NIPAM-co-DMAEMA) hydrogels is carried out when the environmental temperature and pH are changed synchronously. The results show that the model drug Vitamin B12 is released much more rapidly from the comb-type grafted hydrogel than that from the normal-type hydrogel. The proposed dual temperature/pH-sensitive comb-type grafted cationic poly(NIPAM-co-DMAEMA) hydrogel in this study may find various potential applications, e.g., for fabricating rapid-response smart sensors, actuators, and chemical/drug carriers and so on.  相似文献   

14.
A series of pH‐temperature dual stimuli‐responsive random copolymers poly[N,N‐dimethylaminoethyl methacrylate‐co‐poly(poly(ethylene glycol) methyl ether methacrylate][poly(DMAEMA‐co‐MPEGMA)] were synthesized by free radical polymerization. The supramolecular hydrogel was formed by pseudopolyrotaxane, which was prepared with the host‐guest interactions between α‐cyclodextrin (α‐CD) and poly(ethylene glycol) (PEG) side chains. Fourier transform infrared (FT‐IR), nuclear magnetic resonance (1H NMR), and X‐ray diffraction (XRD) confirmed the structures of the hydrogels. The pH‐temperature dual stimuli responsive properties of the hydrogels were characterized by rheometer. Finally, the controllable drug release behavior of the hydrogel, which was used 5‐fluorouracil (5‐Fu) as the model drug, was investigated at different temperatures and different pH values. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43279.  相似文献   

15.
A novel thermo/pH/magnetic-triple-responsive nanogel was synthesized by grafting N-isopropylacrylamide and acrylic acid onto sodium alginate to modify magnetic graphene oxide as a drug delivery system. The synthesized nanogel was characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), vibrating sample magnetometer (VSM), atomic force micrographs (AFM), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The obtained nanogel displayed excellent reversible transmittance changes in response to pH, temperature, and magnetic field. The performance of the nanogels to load doxorubicin (DOX) drug and to sustain doxorubicin release was tested upon exposure to pH, temperature, and magnetic field variations. The mechanism of drug release was proposed in this paper by different kinetic models. In addition, the effects of nanogels and DOX-loaded nanogels on MCF-7 cells were examined and results were compared with free DOX drug. The in vitro results demonstrated that this triple-responsive nanogel can be an appropriate candidate for applications in cancer therapy.  相似文献   

16.
A novel drug-delivery carrier, poly(ethylene glycol) methyl ether methacrylate/2-(diethylamino) ethyl methacrylate/bis (2-methacryloxyethyl) disulfide (PEDS) hydrogel, was prepared with poly(ethylene glycol) methyl ether methacrylate (PEGMA) and amine containing 2-(diethylamino)ethyl methacrylate (DMAEMA) monomers and a disulfide-containing cross-linking agent bis(2-methacryloxyethyl) disulfide (DSDMA). The RN(C2H5)2 in poly(2-(diethylamino)ethyl methacrylate) (PDMAEMA) can be protonated in acidic environments, causing the expansion of the polymer network and promotion of drug release. The presence of the biologically available reducing agent glutathione (GSH) induces disulfide bond cleavage in DSDMA, which initiates the expansion of the polymer networks. The inner morphology dependence on redox and pH conditions for PEDS1 hydrogels was revealed. In neutral solutions without GSH, a pore structure with full, thick walls was observed. In acidic or GSH solutions, the pore structure was destroyed, and the pore cell walls were thin or broken. These changes can induce drug release. Drug release studies were also conducted using berberine as a model drug. The drug released from the hydrogels into the supernatant was measured in both GSH and acidic solutions. PEDS1 hydrogels exhibited a substantial enhancement in release rates in acidic solutions or neutral GSH solutions, suggesting the drug release from PEDS hydrogels is redox- and pH-dependent.  相似文献   

17.
Weizhong Yuan  Sixun Zheng 《Polymer》2007,48(9):2585-2594
A series of well-defined dendritic star-block copolymers were successfully synthesized by combination of living ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP) with the hydroxyl-terminated dendrimer polyester. Dendritic star-shaped poly(l-lactide)s (PLLAs) were prepared by bulk polymerization of l-lactide (l-LA) with dendrimer polyester initiator and tin 2-ethylhexanoate catalyst. The number-average molecular weight of these polymers linearly increased with the molar ratio of l-LA to dendrimer initiator. Dendritic star-shaped PLLA was converted into a PLLABr macroinitiator with 2-bromopropionyl bromide. Dendritic star-block copolymers could be obtained via ATRP of 2-(N,N-dimethylamino)ethyl methacrylate (DMAEMA). The molecular weight distributions of these copolymers were narrow. The molecular weights of dendritic star-shaped polymers and star-block copolymers could be controlled by the molar ratios of monomer to initiator and monomer conversion. The thermal properties of these dendritic star-shaped polymers and star-block copolymers were investigated. The behavior of model drug chlorambucil release from the copolymer indicated that the rate of drug release could be effectively controlled by altering the pH values of the environment.  相似文献   

18.
The experiment and dissipative particle dynamics simulation were carried out on four polymers with different block ratios for the investigation of the structure–property relationship of (poly(ε‐caprolactone)2‐[poly(2‐(diethylamino)ethyl methacrylate)‐b‐poly(poly(ethylene glycol) methyl ether methacrylate)]2 [(PCL)2(PDEA‐b‐PPEGMA)2] micelles. The miktoarm star polymers assembled into spherical micelles composed of PCL core, pH‐sensitive PDEA mesosphere and poly (ethylene glycol) methyl ether methacrylate (PPEGMA) shell. When decreasing pH from 7.4 to 5.0, the hydrodynamic diameter and transmittance of (PCL)2(PDEA‐b‐PPEGMA)2 micelles increased along with globule‐uneven‐extended conformational transitions, owing to the protonation of tertiary amine groups of DEA at lower pH conditions. Doxorubicin (DOX) was mainly loaded in the pH‐sensitive layer, and more DOX were loaded in the core when increasing drug concentrations. The in vitro DOX release from the micelles was significantly accelerated by decreasing pH from 7.4 to 5.0. The results demonstrated that the pH‐sensitive micelles could be used as an efficient carrier for hydrophobic anticancer drugs, achieving controlled and sustained drug release. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3634–3646, 2014  相似文献   

19.
Liang Sun  Jianzhong Du 《Polymer》2012,53(10):2068-2073
Polymer vesicles have been widely explored as drug delivery carriers. However, there are still several notable problems in the determination of the drug loading content (DLC) and the drug loading efficiency (DLE) of the drug delivery vehicles. Presented in this paper is the reconsideration of various important factors in the measurement of the DLC and DLE based on an ‘instant’ biocompatible and biodegradable polymer vesicle which can be directly dissolved in water, with a focus on the study on the time for removing the free drug. Firstly, an anti-cancer drug, doxorubicin (DOX), was successfully encapsulated into a highly biocompatible and biodegradable poly(ε-caprolactone)-block-poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PCL-b-PMPC) diblock copolymer vesicle. Secondly, a specific methodology for removing the unencapsulated drug by dialysis method before the drug release experiment has been established to verify the DLC and the DLE of DOX. A number of important factors have been investigated, such as the period of time for removing the free drug, the temperature and the volume of water outside the dialysis tube, etc. Finally, the DOX release experiment was carried out at pH 5.0 and pH 7.4 with the cumulative release percentages of 55% and 35% after 24 h when the DOX feeding was 1.0 mg. As PCL-b-PMPC vesicles absorb UV light, the DOX encapsulated in polymer vesicles was calculated by subtracting the UV absorbance of vesicle solution from the UV absorbance of DOX-loaded vesicle solution at different DOX feedings of 1.0, 3.0 and 5.0 mg. We also found the appropriate calibration curves at different solution conditions were of great significance for the calculation of DLC and DLE.  相似文献   

20.
A novel stimuli-responsive magnetite nanocomposite as de novo drug delivery system for cancer chemotherapy is developed successfully through the incorporation of magnetite nanoparticles into PEG-b-(PNIPAAm-b-PAA)2 copolymer. The chemical structures of samples were characterized using FTIR and 1H NMR spectroscopies. Furthermore, thermal property, morphology, size, and magnetic properties of the nanocomposite were investigated. The DOX loading and encapsulation efficiencies as well as stimuli-responsive drug release ability of the nanosystem were studied. As results, at pH 5.3 and temperature of 41°C the nanocomposite exhibited higher drug release values, which qualified it for cancer chemotherapy according to especial features of cancerous tissue.  相似文献   

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