pH‐sensitive acrylic‐based copolymeric hydrogels for the controlled release of a pesticide and a micronutrient

Acrylic‐based copolymers of methyl methacrylate (MMA) and methacrylic acid (MAA) have been prepared by solution and bulk polymerization techniques using benzoyl peroxide (BPO) as an initiator. Three polymers were prepared with a varying ratio of MMA/MAA. In an effort to increase the hydrophilicity of the matrix, one MMA/MAA polymer was prepared by adding an additional amount of 2‐hydroxy ethyl methacrylate (HEMA). All the polymers were crosslinked in situ by ethylene glycol dimethacrylate (EGDMA). These polymers were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Viscous flow characteristics were determined from solution viscosity and rheological measurements. Dynamic and equilibrium swelling experiments were carried out under varying pH conditions (i.e., 0.1N NaOH, 0.1N HCl, and double‐distilled water). Partially crosslinked hydrogels show varying hydrophilicity because of the presence of carboxylic acid groups making them pH‐responsive. Swelling increased with an increasing number of —COOH groups on the polymer backbone and the hydrophilicity varied with changing pH. Cypermethrin, a widely used pesticide, and cupric sulfate, a model micronutrient, were loaded into these pH‐sensitive hydrogels to investigate their controlled release characteristics. The in vitro release rates of both compounds have been carried out under static dissolution conditions at 30°C. Release data have been fitted to an empirical relation to estimate transport parameters. The release results have been discussed in terms of the varying hydrophilicity of the hydrogel network polymers. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 394–403, 2003     

Preparation and characterization of a novel pH‐, thermo‐, and ionic strength‐responsive hydrogels based on xanthan gum–poly(aspartic acid)

A series of interpenetrating polymer networks (IPN) hydrogels with different compositions that based on xanthan gum (XG) and poly(aspartic acid) (PASP) were synthesized. The effects of various external surrounding stimuli, including pH, temperature, and ionic strength on XG–PASP hydrogels swelling properties were investigated. Chemical structural changes of the IPN hydrogels were characterized by Fourier transform infrared spectroscopy (FT‐IR), differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and swelling ratio measurement. The swelling process was found to be a Fickian diffusion and reached swelling equilibrium quickly. It was found that the feed composition of PASP was an important factor that affected the properties of IPN hydrogels. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

pH/temperature‐responsive semi‐IPN hydrogels composed of alginate and poly(N‐isopropylacrylamide)

Amino semitelechelic poly(N‐isopropylacrylamide) (PNIPAAm) was prepared by radical polymerization with aminoethanethiol hydrochloride as a chain‐transfer agent. Semi‐interpenetrating polymer network (semi‐IPN) hydrogels, composed of alginate and amine‐terminated PNIPAAm, were prepared by crosslinking with calcium chloride. From the swelling behaviors of semi‐IPNs at various pH's and Fourier transform infrared spectra at high temperatures, the formation of a polyelectrolyte complex was confirmed from the reaction between carboxyl groups in alginate and amino groups in modified PNIPAAm. Semi‐IPN hydrogels reached an equilibrium swelling state within 24 h. The water state in hydrogels, investigated by differential scanning calorimetry, showed that sample CAN55 [alginate/PNIPAAm (w/w) = 50/50] exhibited the lowest equilibrium water content and free water content among the hydrogels tested, which was attributed to its more compact structure compared to other samples and the high content of interchain bonding within the hydrogels. Alginate/PNIPAAm semi‐IPN hydrogels exhibited a reasonable sensitivity to the temperature, pH, and ionic strength of swelling medium. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 1128–1139, 2002     

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.     

Sustained release behavior of pH‐responsive poly(vinyl alcohol)/poly(acrylic acid) hydrogels containing activated carbon fibers

The composites of pH‐responsive poly(vinyl alcohol)/poly(acrylic acid) hydrogel and activated carbon fibers (ACFs) were prepared as sustained drug release system with excellent mechanical properties. The mechanical properties of hydrogels were improved greatly by addition of ACFs. The thinner ACFs were more effective in increasing the mechanical properties of composite hydrogels. The cumulative amount of release and the release period were dependent on the surface area and the pore volume of ACFs. The drug release was maximized at basic condition due to the pH‐sensitive hydrogel matrices and the initial bust phenomenon was alleviated by incorporating ACFs in the hydrogels. The drug release was sustained about four times longer and the mechanical property was increased about 2.6 times higher because ACFs worked as drug reservoir and reinforcement. Cytotoxicity evaluation confirmed the biocompatible characteristics of the ACFs‐containing hydrogels. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

PVA/PAA thermo‐induced hydrogel fiber: Preparation and pH‐sensitive behavior in electrolyte solution

The preparation of thermo‐induced hydrogel fibers composed of poly(vinyl alcohol) and poly(acrylic acid) is presented. The hydrogel fiber was prepared by extruding the spinning dope from in situ polymerization of acrylic acid in the presence of PVA into a coagulating bath of saturated ammonium sulfate aqueous solution. The network was formed by thermally heating the dried fibers under vacuum. The final hydrogel fibers exhibit pH‐sensitive behavior and show a hysteresis loop in the pH range from 3.0 to 12.0. The pH value, at which the swelling elongation ratio of the fiber had a jump, shifted to a lower value with increasing PAA content within the network. Increasing the heating temperature and time for the fibers, decreased the swelling elongation ratio, and the jump point pH shifted to higher pH value. The oscillatory swelling/contracting behavior of the hydrogel fiber exhibited a good reversible pH‐responsive property. Transmission Electron Microscopy (TEM) showed that PVA and PAA have good compatibility and give a relative independent interpenetrating network. Scanning Electron Microscopy (SEM) showed that in the surface of the fibers there were microholes and ditches due to some diffusion of PAA into the coagulating solution. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2423–2430, 2002     

Preparation of quadruple responsive polymeric micelles combining temperature‐, pH‐, redox‐, and UV‐responsive behaviors and its application in controlled release system

A novel series of quadruple responsive copolymers, poly(ethylene glycol)‐ss‐[poly(dimethylaminoethyl methacrylate)‐co‐poly(2‐nitrobenzyl methacrylate)] [PEG‐ss‐(PDMAEMA‐co‐PNBM)], were synthesized via atom transfer radical polymerization mediated by home‐made PEG‐based macro‐initiator labeled with disulfides. The obtained copolymers could self‐assemble in aqueous solution forming micelles with the disulfide bridge linking the hydrophilic coronas (PEG) and the hydrophobic cores (PDMAEMA‐co‐PNBM). Investigation on the resulted micelles indicated that the micelles could respond to various stimuli, that is, temperature, pH, the presence of dithiothreitol (DTT), and UV irradiation. Moreover, the responsive behavior of the micelles depends on the type of stimuli, that is, temperature change causes size change of the micelles, while UV irradiation leads to dissolution of the self‐assembled structures. Such stimulus‐dependent responsive behavior could be applied in smart materials that deal with multi‐tasks or in the construction of complex logic gate. The potential application of the multi‐responsive micelles in cargo release system was also evaluated using Nile Red (NR) as model molecule. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46675.     

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     

Swelling of pH‐sensitive chitosan–poly(vinyl alcohol) hydrogels

The swelling properties of different chitosan–poly(vinyl alcohol) (PVA) hydrogels were investigated as functions of the medium pH and salt concentration. The maximum swelling ability of the hydrogels was at a buffer pH of approximately 3, regardless of the PVA content in the hydrogels. The maximum mass of the swollen hydrogels was about 13 times that of their contracted counterparts. The cyclical swelling and contraction between pH 3 and pH 7 buffers and pH 3 and pH 3 buffers with salt confirmed the Donnan swelling mechanism of these hydrogels. The swelling mechanism was considered the transfer of water molecules driven by a concentration gradient. This was represented by a simplified mass‐balance model, which neglected the effect of the ionization reaction, for the initial swelling period. The effective mass‐transfer coefficient of water molecules during swelling, estimated with this model, gradually decreased with increasing PVA content in the hydrogels. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 4665–4671, 2006     

Preparation and release behavior of temperature‐ and pH‐responsive chitosan material

BACKGROUND: Chitosan is a polymer with good biocompatibility which makes it promising for potential applications in the field of drug delivery. A novel kind of copolymer, P(CS‐Ma‐graft‐NIPAm), was synthesized with chitosan (CS), maleic anhydride (Ma) and N‐isopropylacrylamide (NIPAm) by grafting and copolymerization. RESULTS: The copolymers were characterized using Fourier transform infrared, ¹H NMR and ultraviolet spectroscopies, and the molecular weight and polydispersity were determined using gel permeation chromatography. The aqueous solution properties of the copolymer and the controlled delivery of coenzyme A from it were also studied. The results showed that the copolymer had temperature and pH sensitivities, and that the release of coenzyme A from the copolymer was dependent on the release medium, namely the concentration of the copolymer, pH and temperature. Higher concentrations of the copolymer absorbed more coenzyme A than lower ones. Increasing temperature accelerated coenzyme A release from the copolymer. Also, the pH of the solution had a significant impact on the release of coenzyme A. CONCLUSION: These results suggest that the novel copolymer could be used in drug delivery systems. Copyright © 2007 Society of Chemical Industry     

药物控释用智能水凝胶研究进展

智能水凝胶在药物控释方面具有智能化、效率高和安全方便等优点.近年来,研究开发药物控释用智能水凝胶非常活跃,展示了广阔的应用前景.本文综述了药物控释用温度、pH值、葡萄糖、电场、磁场及光敏感水凝胶的最新研究进展.     

pH‐ and temperature‐responsive IPN hydrogels based on soy protein and poly(N‐isopropylacrylamide‐co‐sodium acrylate)

pH‐ and temperature‐responsive interpenetrating polymer network (IPN) hydrogels based on soy protein and poly(N‐isopropylacrylamide‐co‐sodium acrylate) were successfully prepared. The structure and properties of the hydrogels were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, and thermogravimetric analyzer. The equilibrium and dynamic swelling/deswelling behaviors and the drug release properties of the hydrogels responding to pH and/or temperature were also studied in detail. The hydrogels have the porous honeycomb structures, good miscibility and thermal stability, and good pH‐ and temperature‐responsivity. The volume phase transition temperature of the hydrogels is ca. 40°C. Changing the soy protein or crosslinker content could be used to control the swelling behavior and water retention, and the hydrogels have the fastest deswelling rate in pH 1.2 buffer solutions at 45°C. Bovine serum albumin release from the hydrogels has the good pH and temperature dependence. The results show that the proposed IPN hydrogels may have potential applications in the field of biomedical materials such as in drug delivery systems. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39781.     

Thermo‐ and pH‐responsive microgels for controlled release of insulin

Microgel particles were prepared, made of hydroxypropylcellulose‐graft‐(acrylic acid) (HPC‐g‐AA) and acrylic acid(AA). The particles undergo reversible volume phase transitions in response to both pH and temperature changes while keeping the inherent properties of PAA and HPC‐g‐AA. Dynamic light scattering measurements reveal that the average hydrodynamic radius and hydrodynamic radius distributions of the microgel particles depend on temperature and pH. The microgels exhibit excellent pH sensitivity and a higher swelling ratio at higher pH in aqueous solution. In vitro release study shows that the amount of insulin released from the microgels is less at pH = 1.2 than at pH = 6.8. The results indicate that the resultant microgels seem to be of great potential for intelligent oral drug delivery. Copyright © 2012 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.     

Temperature/pH‐sensitive comb‐type graft hydrogels composed of chitosan and poly(N‐isopropylacrylamide)

Comb‐type graft hydrogels, composed of chitosan and poly(N‐isopropylacrylamide) (PNIPAAm), were prepared to manifest rapid temperature and pH sensitivity. Instead of directly grafting the NIPAAm monomer onto the chitosan chain, semitelechelic PNIPAAm with carboxyl end group was synthesized by radical polymerization using 3‐mercaptopropionic acid as the chain‐transfer agent, and was grafted onto chitosan having amino groups. The comb‐type hydrogels were prepared with two different graft yields and grafting regions, such as surface‐ and bulk‐grafting, and then compared with a chitosan hydrogel. The synthesis of telechelic PNIPAAm and the formation of amide group were confirmed by using FTIR spectroscopy and gel permeation chromatography. Results from the water state and thermal stability revealed that the introduction of the PNIPAAm side chain disturbed the ordered arrangement of the chitosan molecule, resulting in an increase in the equilibrium water content. Comb‐type graft hydrogels showed rapid temperature and pH sensitivity because of the free‐ended PNIPAAm attached to the chitosan main chain and the chitosan amino group itself, respectively. In particular, the surface graft hydrogel maintained its dimension at low pH, although the chitosan main chain was not crosslinked, whereas chitosan and bulk graft hydrogel were dissolved as a result of the coating effect of pH‐independent PNIPAAm. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 2612–2620, 2004     

Biocompatible and biodegradable alginate/poly(N‐isopropylacrylamide) hydrogels for sustained theophylline release

Mixed‐interpenetrated polymeric networks based on sodium alginate (ALG) and poly(N‐isopropylacryl amide) (PNIPAAm) covalently cross‐linked with N,N'‐methylenebisacrylamide are studied for their biocompatibility, nontoxicity, and biodegradability aiming their application in drug delivery. The presence of drug‐polymeric matrix interactions and the distribution of the drug in the polymeric network for theophylline‐loaded ALG/PNIPAAm hydrogels are also investigated by spectroscopic and microscopic methods. The quantitative evaluation of theophylline loaded hydrogels performed by NIR‐CI technique shows a better drug entrapment and a higher homogeneity of the samples with increased alginate content. The thermal behavior of the hydrogels is significantly modified by theophylline presence. The application of the ALG/PNIPAAm hydrogels as carriers for sustained drug release formulations was assessed by the theophylline release tests performed both by in vitro and in vivo studies. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40733.     

A facile preparation of pH‐temperature dual stimuli‐responsive supramolecular hydrogel and its controllable drug release

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.     

Rheological properties and drug release characteristics of pH‐responsive hydrogels

Rheological properties, blend compatibility, and gel‐forming capacity of carbopol 940 (CP‐940), sodium alginate (NaAlg), and guar gum (GG) have been studied. These matrices have been used in delivery of timolol maleate for ophthalmic applications. Aqueous solutions of CP‐940, NaAlg, and GG in concentrations between 0.1 and 1% (wt/vol) and their blends have been prepared. In situ gel forming polymeric solutions have shown an increase in viscosity upon exposure to specific pH, ions, and temperature of the eyeball. Blend miscibility was studied by calculating polymer–polymer interaction parameters using viscosity data. Rheological properties viz., torque, viscosity, shear stress, and shear rate were obtained using a Brookfield rheometer. Viscosities of polymer solutions were obtained by a Schott Gerate viscometer. Rheological data were analyzed using Bingham, Casson Standard, and Casson Chocolate equations. The hydrogels were subjected to ex vivo release studies on timolol maleate through the excised bovine cornea using a modified Franz diffusion cell. Results were compared with the conventional drug solution. The release could be extended when the drug is incorporated into hydrogel‐forming solution. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2057–2064, 2004     

Dual pH‐ and thermal‐responsive nanocomposite hydrogels for controllable delivery of hydrophobic drug baicalein

Hydrogels have been widely used as mild biomaterials due to their bio‐affinity, high drug loading capability and controllable release profiles. However, hydrogel‐based carriers are greatly limited for the delivery of hydrophobic payloads due to the lack of hydrophobic binding sites. Herein, nano‐liposome micelles were embedded in semi‐interpenetrating poly[(N‐isopropylacrylamide)‐co‐chitosan] (PNIPAAm‐co‐CS) and poly[(N‐isopropylacrylamide)‐co‐(sodium alginate)] (PNIPAAm‐co‐SA) hydrogels which were responsive to both temperature and pH, thereby establishing tunable nanocomposite hydrogel delivery systems. Nano‐micelles formed via the self‐assembly of phospholipid could serve as the link between hydrophobic drug and hydrophilic hydrogel due to their special amphiphilic structure. The results of transmission and scanning electron microscopies and infrared spectroscopy showed that the porous hydrogels were successfully fabricated and the liposomes encapsulated with baicalein could be well contained in the network. In addition, the experimental results of response release in vitro revealed that the smart hydrogels showed different degree of sensitiveness under different pH and temperature stimuli. The results of the study demonstrate that combining PNIPAAm‐co‐SA and PNIPAAm‐co‐CS hydrogels with liposomes encapsulated with hydrophobic drugs is a feasible method for hydrophobic drug delivery and have potential application prospects in the medical field. © 2018 Society of Chemical Industry     

Synthesis of biodegradable thermo- and pH-responsive hydrogels for controlled drug release

Novel intelligent hydrogels composed of biodegradable and pH-sensitive poly(l-glutamic acid) (PGA) and temperature sensitive poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (PNH) were synthesized and characterized for controlled release of hydrophilic drug. The influence of pH on the equilibrium swelling ratios of the hydrogels was investigated. A higher PNH content resulted in lower equilibrium swelling ratios. Although temperature had little influence on the swelling behaviors of the hydrogels, the changes of optical transmittance of hydrogels as a function of temperature were marked, which showed that the PNH part of hydrogel exhibited hydrophobic property at temperature above the lower critical solution temperature (LCST). The biodegradation rate of the stimuli-sensitive hydrogels in the presence of enzyme was directly proportional to the PGA content. Lysozyme was chosen as a model drug and loaded into the hydrogels. The in vitro drug release experiment was carried out at different pH values and the release data suggested that both the pH and PNH content played important roles in the drug release behaviors of the hydrogels.