Preparation and characterization of pH-sensitive hydrogel microparticles as a biological on–off switch

The pH-responsive swelling and release behaviors of anionic P(MAA-co-EGMA) hydrogel microparticles having various MAA and EG contents were investigated as a biological on–off switch for the design of an intelligent drug delivery system triggered by external pH changes. When DC was used as a dispersion stabilizer, well-dispersed hydrogel microparticles having an average diameter of approximately 4 μm were obtained. There was a drastic change of the equilibrium weight swelling ratio of P(MAA-co-EGMA) hydrogels at a pH of around 5, which is the pK _a of PMAA. When the MAA content in the hydrogel increased, the swelling ratio increased at a pH above 5 due to the more electrostatic repulsion between the charged groups of MAA. The P(MAA-co-EGMA) hydrogel microparticles showed a pH-responsive release behavior. At low pH (pH 4.0) small amounts of Rh-B were released while at high pH (pH 6.0) relatively large amounts of Rh-B were released from the hydrogels. The difference in the released amount of Rh-B from the hydrogels between pH 4.0 and 6.0 decreased when the MAA content in the hydrogels decreased, which means that the pH-responsive release behavior of the P(MAA-co-EGMA) hydrogel microparticles is closely related to the pH-responsive swelling property of the hydrogel.     

Temperature/pH dual responsive microgels of crosslinked poly(N‐vinylcaprolactam‐co‐undecenoic acid) as biocompatible materials for controlled release of doxorubicin

Undecenoic acid functionalized thermo/pH responsive microgels, poly(N‐vinylcaprolactam‐co‐undecenoic acid) [poly(VCL‐co‐UA)], were synthesized by precipitation emulsion copolymerization. The microgels exhibit reversible thermo/pH responsive phase transition behavior, which can be tuned by varying the monomer feed ratio. The lower critical solution temperatures (LCSTs) of the materials are close to body temperature. As a result, when temperatures rise above ca. 37°C, a rapid thermal gelation process occurs, accompanied by a phase transition, resulting in expulsion of encapsulated compound. In vitro experiment evaluated its applicability as a drug carrier for controlled release of an anticancer agent (doxorubicin) and showed that the drug encapsulation efficiency (EE), releasing rate, and kinetics are dependent on the temperature and pH value as expected. Minimal cytotoxicity of the microgels was observed by a cytotoxicity assay using 3T3 fibroblast cells. Our finding suggests that the poly(VCL‐co‐UA) based microgels may be considered a promising candidate for temperature or pH‐controlled delivery of anticancer drugs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41146.     

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.     

Preparation and characterization of nanostructured and high transparent hydrogel films with pH sensitivity and application

Novel nanostructured, high transparent, and pH sensitive poly(2‐hydroxyethyl methacrylate‐co‐methacryliac acid)/poly(vinyl alcohol) (P(HEMA‐co‐MA)/PVA) interpenetrating polymer network (IPN) hydrogel films were prepared by precipitation copolymerization of aqueous phase and sequential IPN technology. The first P(HEMA‐co‐MA) network was synthesized in aqueous solution of PVA, then followed by aldol condensation reaction, it formed multiple IPN nanostructured hydrogel film. The film samples were characterized by IR, SEM, DSC, and UV‐vis spectrum. The transmittance arrived at 93%. Swelling and deswelling behaviors showed the multiple IPN nanostuctured film had rapid response. The mechanical properties of all the IPN films improved than that of PVA film. Using crystal violet as a model drug, the release behaviors of the films were studied. The results showed that compared with PVA, which had low drug loading and exhibited high and burst release, the three IPN films had high drug loading and exhibited sustained release. Besides, the release followed different release mechanism at pH = 4.0 and pH = 7.4, respectively. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation and application in drug controlled delivery of pH‐sensitive P(CE‐co‐DMAEMA‐co‐MEG) hydrogel

A pH‐sensitive hydrogel [P(CE‐co‐DMAEMA‐co‐MEG)] was synthesized by the free‐radical crosslinking polymerization of N,N‐dimethylaminoethyl methacrylate (DMAEMA), poly(ethylene glycol) methyl ether methacrylate(MPEG‐Mac) and methoxyl poly(ethylene glycol)‐poly(caprolactone)‐methacryloyl methchloride (PCE‐Mac). The effects of pH and monomer content on swelling property, swelling and deswelling kinetics of the hydrogels were examined and hydrogel microstructures were investigated by SEM. Sodium salicylate was chosen as a model drug and the controlled‐release properties of hydrogels were pilot studied. The results indicated that the swelling ratios of the gels in stimulated gastric fluids (SGF, pH = 1.4) were higher than those in stimulated intestinal fluids (SIF, pH = 7.4), and followed a non‐Fickian and a Fickian diffusion mechanism, respectively. In vitro release studies showed that its release rate depends on different swelling of the network as a function of the environmental pH and DMAEMA content. SEM micrographs showed homogenous pore structure of the hydrogel with open pores at pH 1.4. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40737.     

Polyion complex micelles formed by azobenzene-based polymer with multi-responsive properties

Compared with the single polymer micelle system, the polyion complex micellar system is consisted of two or more polymers with different composition, which has more flexible structural adjustment and better performance, making them widely used in drug control release. In this work, two azobenzene-based amphiphilic copolymers P (MMA-co-PEGMA-co-NIPAM-co-HAZOMA) with ionized carboxyl and P (MMA-co-PEGMA-co-NIPAM-co-NNAZOMA) with protonated tertiary amine group were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. We studied self-assembled behavior of polymers and multi-component polymers, including their multiple responsiveness and the encapsulation, controlled release properties of polyion complex micelle. Light, pH, temperature, and reduction responsiveness of three micelles were investigated by UV–vis spectroscopy, transmission electron microscope (TEM), and dynamic light scattering. Compared to RCP 1, and RCP 2, RCP 1/RCP 2 micelle can release Nile red in both acidic and alkaline environment. When temperature reached critical solution temperature, RCP 1/RCP 2 micelle would release Nile red faster. Polyion complex micelle had better release performance compared to single micelles at the same environment, and could release in a wider range pH, making it had more potential applications in biological science field.     

Poly(D,L‐lactide‐co‐glycolide)/poly(ethylenimine) blend matrix system for pH sensitive drug delivery

Poly(D ,L ‐lactide‐co‐glycolide) (PLGA) and poly(ethylenimine) (PEI) were blended and found to form a homogeneous pH sensitive matrix for drug release. Differential scanning calorimetry (DSC) studies of the PLGA/PEI blends showed a single glass transition temperature at all compositions. Fourier transform infrared spectroscopy (FTIR) demonstrated that the PLGA carbonyl peak at 1760 cm^?1 shifted to 1666 cm^?1 as a result of amide bond formation between the two polymers. This was confirmed by ¹³C nuclear magnetic resonance studies. A PLGA/PEI matrix of 90/10 weight ratio was chosen for evaluation for controlled drug release. Both hydrophobic β‐lapachone and hydrophilic rhodamine B showed pH dependent release profiles with faster release kinetics at lower pH values. The observed pH sensitive drug release was mainly attributed to two factors, pH dependent swelling and protonation of the PEI‐PLGA matrix. These results demonstrate utility of a PLGA/PEI matrix and its potential application in pH responsive drug delivery. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 89–96, 2006     

pH‐sensitive swelling and release behaviors of anionic hydrogels for intelligent drug delivery system

The pH‐sensitive swelling and release behaviors of the anionic P(MAA‐co‐EGMA) hydrogels were investigated as a biological on–off switch for the design of an intelligent drug delivery system triggered by external pH changes. There was a drastic change of the equilibrium weight swelling ratio of P(MAA‐co‐EGMA) hydrogels at a pH of around 5, which is the pK_a of poly (methacrylic acid) (PMAA). At a pH below 5, the hydrogels were in a relatively collapsed state but at a pH higher than 5, the hydrogels swelled to a high degree. When the molecular weight of the pendent poly(ethylene glycol) (PEG) of the P(MAA‐co‐EGMA) increased, the swelling ratio decreased at a pH higher than 5. The pK_a values of the P(MAA‐co‐EGMA) hydrogels moved to a higher pH range as the pendent PEG molecular weight increased. When the feed concentration of the crosslinker of the hydrogel increased the swelling ratio of the P(MAA‐co‐EGMA) hydrogels decreased at a pH higher than 5. In release experiments using Rhodamine B (Rh‐B) as a model solute, the P(MAA‐co‐EGMA) hydrogels showed a pH‐sensitive release behavior. At low pH (pH 4.0) a small amount of Rh‐B was released while at high pH (pH 6.0) a relatively large amount of Rh‐B was released from the hydrogels. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

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     

Biodegradable polyesterurethane networks for controlled release of aspirin

In this article, poly(D,L‐lactide‐co‐glycolide)urethane (PULG) networks were prepared from hydroxyl telechelic star‐shaped oligo(D,L‐lactide‐co‐glycolide) coupled with 1,6‐diisocyanate‐2,2,4‐trimethylhexane and 1,6‐diisocyanate‐2,4,4‐trimethylhexane or isophorone diisocyanate. The release of model drug aspirin (ASP) from biodegradable polyesterurethane networks was studied in phosphate buffered saline pH = 7.0 at 37°C. PULG networks turned from transparent to opaque after ASP loading. PULG networks with lower crosslinking density always resulted in higher drug loaded content. The results of differential scanning calorimetry and scanning electron microscope measurements demonstrated that ASP was uniformly distributed in the networks. The drug release courses of ASP from PULG networks in phosphate buffered saline pH = 7.0 at 37°C could be divided into three stages. Firstly, ASP release was at approximately uniform rate from PULG networks; Secondly, the release rate obviously increased due to the degradation of the PULG networks; Thirdly, the release rate decreased gradually because most of the ASP had diffused out of the PULG networks. The crosslinking density of polyesterurethane networks also affected both degradation of the polymer networks and drug release rate. The in vitro release test revealed that ASP accelerated the degradation process of PULG, which exhibited a typical erosion‐controlled release mechanism. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

PMMA‐based microgels for controlled release of an anticancer drug

Methyl methacrylate (MMA), methoxy poly(ethylene glycol) monomaleate (MPEG), and acrylamidoglycolic acid (AGA) terpolymeric microgels (MGs) have been synthesized by free‐radical surfactant‐free emulsion polymerization. MPEG was synthesized from maleic anhydride and methoxy poly(ethylene glycol). The MGs were crosslinked with ethylene glycol dimethacrylate, and the chemical crosslinking was confirmed by Fourier transform infrared spectroscopy. 5‐Fluorouracil (5‐FU), a model anticancer drug, has been loaded into the MGs by in situ and adsorption methods. Empty as well as drug‐loaded MGs were then characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and X‐ray diffraction (XRD). DSC and XRD studies indicated a molecular level dispersion of the drug in PMMA MGs during in situ loading. TEM images showed the formation of spherical MGs. In vitro release of 5‐FU from the crosslinked poly(MMA‐co‐AGA‐co‐MPEG) MGs were investigated at both pH 7.4 and 1.2 buffer medium that controlled release of the drug up to ～ 18 h. Both the encapsulation efficiency and the release patterns were dependent on the amount of crosslinking agent and the amount of drug loaded. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Independent control of lower critical solution temperature and swelling behavior with pH for poly(N‐isopropylacrylamide‐co‐maleic acid)

Polymer solutions that gel in response to changes in temperature and pH are of interest for various forms of drug delivery, and it is desirable to increase swelling for diffusion‐controlled release without bringing the lower critical solution temperature (LCST) above 37°C. N‐isopropylacrylamide (NIP) was polymerized with maleic acid (MAc), a diprotic acid, and acrylic acid (AAc), a monoprotic acid, to compare swelling and temperature response with changes in pH. For samples with equal acid contents and almost identical LCST responses to pH, poly(N‐isopropylacrylamide‐co‐maleic acid) (pNIP MAc) demonstrated greater swelling than poly(N‐isopropylacrylamide‐co‐acrylic acid) (pNIP AAc). The LCST increase for MAc occurred at a pH corresponding to the deprotonation of almost all of the first acid groups. Further increases in pH led to the deprotonation of the second ? COOH and only served to increase the charge concentration at a given location. These results provide strong support for the theory that LCST results largely from uninterrupted chain lengths of NIP and that swelling results from the actual charge density of acid groups along the chain. Because the use of a diprotic acid copolymer allows swelling to be decoupled from LCST, pNIP MAc may be an appropriate candidate for pH‐sensitive drug‐delivery applications. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2110–2116, 2004     

Self-assembling polyether-b-polymethacrylate graft copolymers loaded with indomethacin

The amphiphilic graft copolymers containing polyether-b-polymethacrylate side chains are proposed as carriers for a nonsteroidal anti-inflammatory drug, indomethacin (IMC). Two series of copolymers, poly((methyl methacrylate)-co-(poly(ethylene glycol methacrylate)-graft-poly((methacrylic acid)-co-(tert-butyl methacrylate)))) (P(MMA-co-(PEGMA-graft-P(MAA-co-tBMA)))) and poly((methyl methacrylate)-co-(poly(propylene glycol methacrylate)-graft-poly((methacrylic acid)-co-(tert-butyl methacrylate)))) (P(MMA-co-(PPGMA-graft-P(MAA-co-tBMA)))) were applied in the micellization process. The effects of grafting degree (5–15%), length of the graft polymethacrylic segments (29–186?units), composition (PEG vs. PPG), and content of acidic fraction (52–89%) were verified in the design of two different types of micelles (depending on polyether nature) with proper stability and controlled release of the drug. The methacrylic segment with MAA units resulted in negatively charged layer as it was indicated by measurements of zeta potential (from ?2 to ?44?mV) The sizes of particles were in the range of 160–225?nm. The type of polyether segment influenced on the content of the drug encapsulation (PEG 39% vs. PPG 93% at 48% of hydrophobic fraction). In vitro experiments demonstrated significantly larger IMC releasing at pH 7.4 than in acidic conditions. The lower drug release rates were monitored for copolymers with long side chains containing large content of acidic units, what enhanced particle stabilization and drug-polymer interactions. The drug release profiles were well fitted to the Higuchi model, suggesting diffusion mechanism. The results confirmed that the graft copolymers might be applied as the carriers releasing a various doses of drug with the rate, which can be adjusted by wider sort of structural parameters than is possible in linear amphiphilic copolymers.     

Poly(acrylic acid‐co‐acrylamide‐co‐2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid)‐grafted nanocellulose/poly(vinyl alcohol) composite for the in vitro gastrointestinal release of amoxicillin

Superabsorbent polymer composites (SAPCs) are very promising and versatile materials for biomedical applications. This study concentrates on the development of novel cellulose‐based SAPC, Poly(acrylic acid‐co‐acrylamide‐co?2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid)‐grafted nanocellulose/poly(vinyl alcohol) composite, P(AA‐co‐AAm‐co‐AMPS)‐g‐NC/PVA, as a potential drug delivery vehicle. Amoxicillin was selected as a model drug, which is used for the treatment of Helicobacter pylori induced peptic and duodenal ulcers. P(AA‐co‐AAm‐co‐AMPS)‐g‐NC/PVA was synthesized by graft copolymerization reaction, and FTIR, XRD, SEM, and DLS analyses were performed for its characterization. Equilibrium swelling studies were conducted to evaluate the stimuli‐response behavior of the SAPC and found that equilibrium swelling was dependent on pH, contact time, temperature, ionic strength, concentration of crosslinker and PVA. Maximum drug encapsulation efficiency was found out by using different concentrations of amoxicillin. Drug release studies were carried out at simulated gastric and intestinal fluids and the release % was observed as maximum in intestinal fluids within 4 h. The drug release kinetics was investigated using Peppas' potential equation and follows non‐Fickian mechanism at pH 7.4. Thus, the drug release experiments indicate that P(AA‐co‐AAm‐co‐AMPS)‐g‐NC/PVA would be a fascinating vehicle for the in vitro administration of amoxicillin into the gastrointestinal tract. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40699.     

Synthesis,characterization and application of poly[(1‐vinyl‐2‐pyrrolidone)‐co‐(2‐hydroxyethyl methacrylate)] as controlled‐release polymeric system for 2,4‐dichlorophenoxyacetic chloride using an ultrafiltration technique

BACKGROUND: Polymers supporting chemicals used in agriculture have recently been developed to overcome the serious environmental problems of conventional agrochemicals. The success of these formulations is based on a suitable choice of polymer support. Degradable polymeric hydrogels are of particular interest. The gradual release of the bioactive agent can be achieved by hydrolytic or enzymatic cleavage of the linking bond. RESULTS: In this context, poly[(1‐vinyl‐2‐pyrrolidone)‐co‐(2‐hydroxyethyl methacrylate)] [poly(NVP‐co‐HEMA)] has been used as a bioactive carrier reagent. Herein, we report a controlled‐release system with the herbicide 2,4‐dichlorophenoxyacetic acid (2,4‐D) using an ultrafiltration system. Hydrolysis was studied by testing the release at various pH values. A high release with poly(NVP‐co‐HEMA)–2,4‐D was observed at pH = 7 and 10 after two days (Z = 2). The release percentage of copolymer–herbicide increased at pH = 10. It showed release values between 79.0 and 94.5%. Poly(NVP‐co‐HEMA)–herbicide can release a bioactive compound in aqueous solution at pH = 3, 7 and 10. CONCLUSION: Based on the results of homogeneous hydrolysis, it is argued that the herbicide release rate depends on the pH of the reaction environment. This functional polymer could be employed as a biodegradable material for applications in agrichemical release. Copyright © 2008 Society of Chemical Industry     

Temperature and pH responsive hydrogels based on polyethylene glycol analogues and poly(methacrylic acid) via click chemistry

A novel temperature responsive copolymer, poly[2‐(2‐methoxyethoxy)ethyl methacrylate‐co‐oligo(ethylene glycol)methacrylate‐co‐N‐hydroxymethyl acrylamide] [P(MEO₂MA‐co‐OEGMA‐co‐HMAM)], was synthesized by atom transfer radical polymerization. pH responsive poly(methacrylic acid) (PMAA) was synthesized by reversible addition‐fragmentation chain transfer polymerization. After the hydroxyl groups on P(MEO₂MA‐co‐OEGMA‐co‐HMAM) were transformed into azide groups and the carboxyl groups on PMAA were transformed into alkyne groups respectively, a novel temperature and pH responsive hydrogel was fabricated by click chemistry between the azide‐P(MEO₂MA‐co‐OEGMA‐co‐HMAM) and alkyne‐PMAA in the presence of CuSO₄ and sodium ascorbate in aqueous solution. The rheological kinetics of gel formation demonstrated that gelation had commenced within 5 min at 25 °C, since then the storage modulus (G′) was higher than the loss modulus (G″). SEM images of hydrogel morphology and the swelling ratios of hydrogel at different temperatures and pH proved that the formed hydrogel had temperature and pH sensitivities. Bovine serum albumin was used as a model to evaluate the sustained release of the hydrogel; the results indicated that the hydrogel was a promising candidate for controlling protein drug delivery. © 2015 Society of Chemical Industry     

Effect of the anionic‐group/cationic‐group ratio on the swelling behavior and controlled release of agrochemicals of the amphoteric,superabsorbent polymer poly(acrylic acid‐co‐diallyldimethylammonium chloride)

A series of amphoteric, superabsorbent polymers [poly(acrylic acid‐co‐diallyldimethylammonium chloride)] with different molar ratios of anionic groups to cationic groups were prepared by solution polymerization to investigate their swelling behaviors and the controlled release of agrochemicals. Various factors, including the solution pH, the concentrations of different salt solutions, and the temperature, were studied. The dynamic parameters of hydrogels at different temperatures suggested that diffusion was Fickian at lower temperatures, whereas non‐Fickian diffusion prevailed at higher temperatures. A copolymer hydrogel with a low anionic‐group/cationic‐group ratio showed a higher swelling capacity in water and higher salt tolerance. Also, the anionic‐group/cationic‐group ratio was not the dominant factor in determining the water retention. A poly(acrylic acid‐co‐diallyldimethylammonium chloride) hydrogel could control the release of agrochemicals effectively. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 986–991, 2006     

Synthesis and properties of polycarbonate copolymers of trimethylene carbonate and 2‐phenyl‐5,5‐bis(hydroxymethyl) trimethylene carbonate

The polycarbonate copolymers poly[trimethylene carbonate‐co‐2‐phenyl‐5,5‐bis(hydroxymethyl) trimethylene carbonate] [P(TMC‐co‐PTC)] were synthesized by the ring‐opening polymerization of trimethylene carbonate (TMC) and 2‐phenyl‐5,5‐bis(hydroxymethyl) trimethylene carbonate (PTC) with tin(II) 2‐ethylhexanoate and aluminum isopropoxide as the catalysts. These copolymers were further reduced by a palladium/carbonate (Pd/C; 10%) catalyst to produce partly deprotected copolymers. These two types of copolymers were characterized by ¹H‐NMR, Fourier transform infrared spectroscopy, UV spectroscopy, gel permeation chromatography, differential scanning calorimetry, and an automatic contact angle meter. The influences of the feed molar ratio of the monomers, the catalyst concentration, the reaction time, and the reaction temperature on the copolymerization process were also studied. The copolymerization of the TMC and PTC monomers was a nonideal copolymerization, and the copolymerization reactivity ratio of TMC was higher than that of PTC. In vitro degradation tests indicated that the partly deprotected copolymers possessed faster degradation rates and more hydrophilicity than the corresponding unreduced copolymers. Moreover, the degradation of these two type copolymers increased when the pH value of the buffer solutions decreased. In vitro drug‐release experiments showed that these two types of copolymers had steady drug‐release rates and good controlled release properties. Moreover, the partly deprotected copolymers had faster drug‐release rates than the corresponding unreduced copolymers. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Encapsulation of diclofenac sodium with acidic copolymer hydrogels based on PEG/poly(N‐isopropylacrylamide‐co‐2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid) semi‐interpenetrating network using in situ loading technique

A pH‐ and temperature‐responsive semi‐interpenetrating copolymer PEG6000/poly(NIPA‐co‐AMPS) (PEG/AMPS‐co‐NIPA SIPN), for short PEG SIPN, was made by ammonium persulfate‐initiated suspension copolymerization of N‐isopropylacrylamide, 2‐acrylamido‐2‐methylpropanesulphonic acid, and N,N′‐methylene‐bis‐acrylamide (MBAA; crosslinker) in the presence of PEG6000. The PEG SIPN copolymer matrices containing nanostructures made in the high‐temperature copolymerization resulted in channels for PEG and facile migration of drugs. In drug encapsulation or drug‐loading process, one can easily ignore or pay less attention to the interaction between a drug and its encapsulation materials; however, the ignored interactions may induce problems in drug properties or the release behavior in use. Sodium diclofenac (DFNa) precipitates as the carboxylic acid form in an acidic environment, and it is challenging to encapsulate sodium diclofenac in such an acidic matrix without precipitation of the sparingly soluble acid form of DFNa on the surface of the polymer substrate. To avoid bulky precipitation in drug loading, an in situ loading technique was developed for producing gel spheres with DFNa uniformly distributed in the polymer matrix. The technique is based on fast polymerization of spherical droplets of a pregel solution in which the drug is dissolved. Diffusion‐loading prodrugs were made in comparison with in situ loading prodrugs in thermal, release kinetics, and release behavior. Drug release profiles (in pH 7.4 phosphate buffer) show that the new drug loading technique gives controlled release during a period of about 7 days at 37°C. By contrast, gel spheres loaded with sodium diclofenac using the conventional diffusion technique produced almost total release of the drug within about 24 h. The thermal stability of sodium diclofenac, the PEG/AMPS‐co‐NIPA SIPN, and the prodrugs made with the SIPN and sodium diclofenac was studied. A near zero‐order release kinetics was found in the in vitro release of sodium diclofenac with in situ loading PEG SIPN prodrug. We have, for the first time, studied sodium diclofenac release behavior from the PEG SIPN hydrogel systems. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Swelling,pH sensitivity,and mechanical properties of poly(acrylamide‐co‐sodium methacrylate) nanocomposite hydrogels impregnated with carboxyl‐functionalized carbon nanotubes

A series of novel nanocomposite hydrogels were prepared by a cross‐linking copolymerization method. Structural and morphological characterizations of the nanocomposite hydrogels revealed that a good compatibility exists between poly(acrylamide‐co‐sodium methacrylate) [P(AM‐co‐SMA)] and carboxyl‐functionalized carbon nanotubes (MWNTs–COOH). The P(AM‐co‐SMA)/MWNTs–COOH nanocomposite hydrogels with a suitable MWNTs–COOH loading exhibited better swelling capability, higher pH sensitivity, good reversibility, and repeatability, and rapid response to external pH stimuli, compared with the P(AM‐co‐SMA). The compression mechanical tests revealed that the nanocomposite hydrogel displayed excellent compressive strengths and elastic mechanical properties, with higher ultimate compressive stress, and meanwhile still retain a good recoverable strain in the presence of MWNTs–COOH. These excellent properties may primarily be attributed to effectively dispersing of a suitable MWNTs–COOH loading into the matrix of the polymers and formation of additional hydrogen bonds. The nanocomposite hydrogels were expected to find applications in drug controlled release and issue engineering. POLYM. COMPOS., 2012. © 2012 Society of Plastics Engineers