Poly(4‐vinyl pyridine)‐grafted graphene oxide for drug delivery and antimicrobial applications

Graphene oxide (GO) was covalently functionalized with poly(4‐vinyl pyridine) (P4VP) by atom transfer radical polymerization for drug delivery and antimicrobial applications. The physiochemical properties, chemical structure, composition and morphology of the P4VP‐functionalized GO (GO‐P4VP) were studied. Simple physisorption of a cancer drug, camptothecin (CPT), via π ? π stacking and/or hydrophobic interactions on the GO‐P4VP was tested for drug loading and its release by altering the pH. The GO‐P4VP has low cytotoxicity, and the CPT‐loaded GO‐P4VP exhibited a high potency for killing cancer cells in vitro. Prominent antimicrobial properties against Escherichia coli and Staphylococcus aureus were also observed. Thus, the GO‐P4VP can be utilized as a drug delivery vector with high biocompatibility, solubility and stability in physiological solutions, a suitable payload capacity and excellent bacterial toxicity. Owing to its small size, low cost, large specific area, ready scalability and useful non‐covalent interactions, GO‐P4VP is a novel material for biomedical, industrial and environmental applications. © 2015 Society of Chemical Industry     

Dual epigallocatechin gallate and camptothecin loaded electrospun meshes for synergy combination chemotherapy of colon cancer

Combination chemotherapy based on electrospun fibrous was a promising strategy to applied synergy effects in treatment for colon cancer. Herein, Lactic acid/glycolic acid (PLGA) meshes with different ratios of epigallocatechin gallate (EGCG) and camptothecin (CPT) were manufactured. Results of X-ray diffraction (XRD) revealed both EGCG and CPT were amorphous in meshes. Drug release experiments indicated that EGCG and CPT could be released sustainably while the dual drug-loaded meshes had a higher release rate than single drug-loaded meshes. Importantly, these meshes displayed obvious cytotoxicity against CT-26 cells in anti-colon cancer experiments, and the combination index values of all dual drug-loaded meshes were around 0.5, suggesting strong synergy effect of EGCG and CPT. These results showed dual EGCG and CPT loaded meshes had application potential in effective synergistic therapy for colon cancer.     

Rheological Aspects and Extension‐Induced Phase Separation in Electrospinning of Poly(N‐isopropyl acrylamide) Solutions in Dimethylformamide

Solutions of poly(N‐isopropyl acrylamide) in dimethylformamide are used to study the relation between the rheological properties and electrospinning behavior. Light scattering of electrospinning jet is conducted to obtain the jet diameter at the straight jet end, from which the average extension rate of the jet is derived based on a simple approach. The extension rate is found to be higher than the terminal relaxation rate of polymer chains determined from the dynamic rheological properties. Based on this finding, the original single‐phase polymer solutions may undergo extensional flow‐induced phase separation in the straight jet section during electrospinning. String‐like structures in the liquid jet as well as in the solid fiber are observed by OM, SEM, TEM, and AFM to validate the hypothesis. The inhomogeneity in the jet, due to the presence of dissipative string structures, may serve as the potential precursor to produce lateral perturbations of jet motion to initiate the macroscopic bending instability at the straight jet end for the jet whipping. Moreover, the formation of the beaded fiber, that is, beads‐on‐a‐string structures, is likely relevant with the dissipative structures developed in the jet, besides the Rayleigh instability of the jet arising from surface tension.     

Thermal properties and crystalline structure of liquid crystalline poly(ethylene terephthalate‐co‐2(3)‐chloro‐1,4‐phenylene terephthalate)

Thermal properties and crystalline structure of liquid crystalline (LC) poly(ethylene terephthalate‐co‐2(3)‐chloro‐1,4‐phenylene terephthalate) [copoly(ET/CPT)] were investigated using differential scanning calorimetry (DSC), thermogravimetry (TGA), limiting oxygen index (LOI) measurement, electron dispersive X‐ray analysis (EDX), X‐ray diffractometry, and infrared spectrometry (IR). The thermal transition temperatures of copoly(ET/CPT) were changed with the composition. Copoly(ET/CPT) showed two thermal decomposition steps and the residues at 700°C and LOI values of copoly(ET/CPT) were almost proportional to its chlorine content. The activation energy of thermal decomposition of LC units was very low compared to that of poly(ethylene terephthalate)(PET) units. Crystal structure of copoly(ET/CPT) (20/80) was of triclinic system with the lattice constants of a = 9.98 A?, b = 8.78 A?, c = 12.93 A?, α = 97.4°, β = 96.1°, and γ = 90.8°, which is very close to that of poly(chloro‐p‐phenylene terephthlate) (PCPT) with the lattice constants of a = 9.51 A?, b = 8.61 A?, c = 12.73 A?, α = 96.8°, β = 95.4°, and γ = 90.8°. When copoly(ET/CPT)(50/50) was annealed at 220°C in vacuum, crystallization induced sequential reordering (CISR) was not observed but the heat of fusion was slightly increased due to the increase of the trans isomer content in PET units. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 1286–1294, 2002; DOI 10.1002/app.10451     

Alignment‐Improved and Diameter‐Reduced Electrospun Polymer Fibers via the Hot‐Stretching Process

Electrospinning is one of the most facile and versatile techniques to prepare polymer fibers ranging from micrometers to nanometers. Although several parameters can be tuned to control the sizes and morphologies of electrospun fibers, many obstacles are still encountered as the target sizes of the fibers are getting smaller; for example, the sizes of the fibers can be effectively reduced by lowering the polymer solution concentrations but beaded or beads‐on‐string structures are usually formed. To overcome such obstacles, here a simple technique to prepare alignment‐improved and diameter‐reduced fibers without bead formation by hot‐stretching electrospun fibers at temperatures higher than the glass transition temperatures of the polymers is developed. Polystyrene and poly(methyl methacrylate) are both used in this work as model materials. The relationship between the draw ratio and diameter of the fibers is quantitatively analyzed, demonstrating the control of the fiber diameters. Moreover, higher degrees of alignment improvement at the middle part of the fibers than those at the end part is observed, which results in lower water contact angles at the middle part of the fibers. This work provides a useful post‐treatment technique to control the sizes and orientations of electrospun polymer fibers.     

Copolymer‐induced silk‐based hydrogel with porous and nanofibrous structure

A novel physical blend method was developed to accelerate the self‐assembly process of silk fibroin (SF) solution into porous and nanofibrous hydrogel by temperature‐sensitive copolymer. Silk‐based hydrogel was firstly achieved through blending SF solution with copolymer aqueous solution and then removed the copolymer from blend solution by heat treatment (50°C) after 24 h hydrogelation. Copolymer molecules would interact with SF molecules resulting in reduction of copolymer micelles, which further affect the hydrogelation of SF solutions. Copolymers could be separated from blend solution by heat treatment under an acceptable temperature (50°C), especially the copolymer₂. Fourier transform infrared (FTIR) and X‐ray diffraction showed the blending of copolymer significantly accelerated the self‐assembly of SF into physically crosslinked β‐sheet crystals at room temperature which led to the sol‐gel transition. Results from DTA and X‐ray diffraction showed that the effect of copolymer on crystalline structure of SF in silk‐based hydrogel was very weak. SF molecules transformed from distributed globular nanoparticles to nanofilaments clustered during hydrogelation, resulting in the porous and nanofibrous structure of silk‐based hydrogel. Furthermore, silk‐based hydrogel was prepared in aqueous solution avoiding organic solvents and harsh processing conditions, suggesting that this silk‐based hydrogel could be a potential candidate scaffold for biomedical applications. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Thermosensitive self‐assembly micelles from A2BA2‐type poly(N‐isopropyl acrylamide)2‐b‐Poly(lactic acid)‐b‐Poly(N‐isopropyl acrylamide)2 four‐armed star block copolymers and their applications as drug carriers

A novel A₂BA₂‐type thermosensitive four‐armed star block copolymer, poly(N‐isopropyl acrylamide)₂‐b‐poly(lactic acid)‐b‐poly(N‐isopropyl acrylamide)₂, was synthesized by atom transfer radical polymerization and characterized by ¹H‐NMR, Fourier transform infrared spectroscopy, and size exclusion chromatography. The copolymers can self‐assemble into nanoscale spherical core–shell micelles. Dynamic light scattering, surface tension, and ultraviolet–visible determination revealed that the micelles had hydrodynamic diameters (D_h) below 200 nm, critical micelle concentrations from 50 to 55 mg/L, ζ potentials from ?7 to ?19 mV, and cloud points (CPs) of 34–36°C, depending on the [Monomer]/[Macroinitiator] ratios. The CPs and ζ potential absolute values were slightly decreased in simulated physiological media, whereas D_h increased somewhat. The hydrophobic camptothecin (CPT) was entrapped in polymer micelles to investigate the thermo‐induced drug release. The stability of the CPT‐loaded micelles was evaluated by changes in the CPT contents loaded in the micelles and micellar sizes. The MTT cell viability was used to validate the biocompatibility of the developed copolymer micelle aggregates. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 4137–4146, 2013     

Adsorption Behavior of Halogenated Anesthetic and Water Vapor on Cr‐Based MOF (MIL‐101) Adsorbent. Part II. Multiple‐Cycle Breakthrough Tests

Multiple‐cycle breakthrough tests of a binary gas mixture of the halogenated anesthetic sevoflurane (SF) and water vapor were performed on both the synthesized chromium‐based metal organic framework (Cr‐MOF) and a conventionally used reference adsorbent. At 1 vol % SF and 50 % relative humidity mixture composition, the Cr‐MOF (MIL‐101) showed a significantly higher SF adsorption capacity, lower water vapor adsorption capacity, and no roll‐up effect compared to the reference sample. After each adsorption measurement, the saturated column was regenerated. MIL‐101 showed higher stability with minor SF capacity loss after 14 cycles, while the reference sample lost about a half of the SF capacity after 17 cycles.     

Influence of the Salt Concentration on the Properties of Salt‐Free Polyelectrolyte Complex Membranes

Polyelectrolyte complexes (PECs) prepared by solution mixing of cationic poly(diallyldimethylammonium chloride) and anionic poly(sodium 4‐styrene sulfonate) with various NaCl content are processed into films. Salt‐free (SF‐PEC) membranes are produced by rinsing the PEC in water overnight. The main finding of this paper is that SF‐PEC films have different properties depending on the NaCl concentration used during the processing step. Dynamic mechanical analysis measurement confirms that hydrated SF‐PEC film processed from higher salt content has a higher modulus than when processed without salt and the glass transition temperature appears to shift to higher values. Processing the PECs films in the presence of salt also has an interesting effect on their shape memory characteristics. SF‐PEC films prepared with high‐salt concentration are shown to maintain a programmed temporary shape better than materials prepared with low salt, while recovery is possible within a short period of time when immersed in hot water.     

Study on the formation and structural evolution of bead‐on‐string in electrospun polysulfone mats

Bead‐on‐string is a desirable morphology for some emerging applications of electrospun mats such as superhydrophobic surfaces. In this study, the bead‐on‐string morphology in electrospun polysulfone (PSU) mats was investigated and correlated with the solution concentration, voltage and feed rate. PSU/dimethylformamide solutions with different concentrations (4, 5.5, 7, 15, 18 and 20 wt% PSU) were electrospun at a constant feed rate (3.5 mL h^–1) and voltage (15 kV). Critical chain overlap and entanglement concentrations were found to be 3.65 and 7.12 wt% PSU, respectively. The bead‐on‐string morphology was detected in the concentration range 7–18 wt% PSU, in close agreement with theoretical estimations. The evolution of the bead‐on‐string morphology in mats prepared from 15 wt% PSU solution and electrospun at three feed rates (i.e. 1.5, 2.5 and 3.5 mL h^–1) and voltages (i.e. 12.5, 15 and 18 kV) were also studied. The results showed that the beads appear less in number as either the feed rate or the voltage increases. In addition, the morphology of the beads revealed a transition from a spherical to a spindle‐like appearance with an increase in voltage. The effect of feed rate on bead geometry, however, was revealed to depend on the applied voltage. © 2020 Society of Chemical Industry     

Development of a thermosensitive grafted drug delivery system—synthesis and characterization of NIPAAm‐based grafts and hydrogel structure

A thermosensitive grafted hydrogel was investigated for heating‐activated drug release. The hydrogel was created by grafting oligomers of N‐isopropylacrylamide‐co‐acrylamide (AAm) to a poly(2‐hydroxyethyl methacrylate), or PHEMA, hydrogel. N‐Isopropylacrylamide‐co‐AAm oligomers were synthesized with a range of compositions to raise the lower critical solution temperature (LCST) above physiological temperature. PHEMA hydrogels with these thermosensitive grafts were synthesized by free‐radical solution polymerization, using an acrylated version of the oligomers. The oligomers were characterized for their molecular weight, LCSTs, and rate of response to a change in temperature. With the flexibility in tuning their properties by varying reaction parameters, these oligomers present possibilities in several fields, including drug delivery. The impact of cross‐linking agent type and the amount and presence of grafts on the polymer network structure was found by determining the hydrogel mesh sizes. PHEMA gels cross‐linked with methylenebisacrylamide had larger mesh sizes than those cross‐linked with ethylene glycol dimethacrylate. Increasing amounts of cross‐linking agent decreased mesh sizes. LCSTs exhibited by oligomers were slightly lower than those exhibited by polymer gels of the same composition. The grafting reaction was found to have only a slight impact on the hydrogel mesh size. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

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     

Development of pH‐sensitive nanogels for cancer treatment using crosslinked poly(aspartic acid‐graft‐imidazole)‐block‐poly(ethylene glycol)

pH‐sensitive nanogels (NGs) based on poly(aspartic acid‐graft‐imidazole)‐poly(ethylene glycol) were developed using linear PEG with different molecular weights (2000 and 4000 Da) as crosslinkers. The pH‐sensitive NGs showed reversible size changes during continuously alternating pH changes. The anticancer treatment potential of pH‐sensitive NGs was studied using a model drug, irinotecan (IRI). IRI‐loaded NGs (ILNs) showed different drug release kinetics in acidic versus neutral pH, in addition to pH‐dependent cytotoxicity. Due to its longer crosslinker, ILN 4 (crosslinked with PEG 4000) showed faster IRI release and a greater magnitude of IRI release than ILN 2 (crosslinked with PEG 2000), resulting in greater cytotoxicity against HCT 116 colorectal cancer cells. These pH‐sensitive NGs could potentially be used in cancer treatment by mediating the accumulation and release of IRI from ILNs in the acidic tumor environment and by reducing systemic toxicity due to reversible swelling–shrinkage. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46268.     

Morphology and mechanical properties of PVC/straw‐fiber coated with liquid nitrile‐butadiene rubber composites

This study exhibited an approach of high‐value utilization of straw fiber (SF) in polymer composites. The rigid poly(vinyl chloride) [PVC]/SF and PVC/SF coated with liquid nitrile‐butadiene rubber (PVC/LNBR‐SF) composites were both fabricated by melt mixing. The chemical structure and crystal structure of LNBR‐SF were characterized by Fourier Transform Infrared Spectroscopy (FTIR) and X‐ray diffraction (XRD). The mechanical properties and micro‐structure of PVC/SF and PVC/LNBR‐SF composites were also studied. FTIR and XRD results showed that the chemical structure and crystal structure of SF did not change after modifying with LNBR. The mechanical properties analysis showed that the PVC/LNBR‐SF composites exhibited better tensile strength, elongation at break and notched impact strength than those of PVC/SF composites owing to the compatibilization and toughening effect of LNBR. Scanning electron microscope results indicated that the LNBR improved the dispersion of SF in PVC matrix to some extent. The interface adhesion between SF and PVC matrix with adding LNBR was also enhanced. These results suggested that PVC/LNBR‐SF composites exhibited promising potential for practical application in substitute for wood. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44119.     

Magnetic‐induced coil‐globule transition for polyelectrolytes

The effects of an applied magnetic field on the system composed of polyelectrolytes (PEs) and magnetic nanoparticles oppositely charged are studied by means of Monte Carlo method within the framework of “single‐site bond fluctuation model.” For a certain concentration of chains, the coil‐globule transition can be induced by the applied magnetic field. The mean‐square end‐to‐end distance and gyration radius as well as the shape factor of PE chains are used to characterize the conformational transitions. The statistical analysis of the system energy demonstrates this significant physical process. The role of entropy‐energy balance is well‐understood for different chain lengths, and a typical phase‐transition anomaly concerned with specific heat curve is observed. Under a certain magnetic field, the PE chains will regularly collapse due to the enough adsorption of magnetic particles. The magnetic particles exhibit peculiar spatial distribution at high magnetic fields: the string‐like arrangement along the magnetic field and the square lattice‐like arrangement perpendicular to the magnetic field. The applied magnetic field has a great influence on the length of string‐like structures formed by nanoparticles. This investigation may cast light on the collapse of PEs and provide a promising method for producing new nanocomposites. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Synthesis and characterization of amphiphilic pluronic (F68)‐1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphoethanolamine copolymers and their micelles as a drug carrier

A new Pluronic (F68)‐1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphoethanolamine (DPPE) (Pluronic (F68)–DPPE) copolymer was synthesized with Pluronic (F68) and DPPE. The chemical structure and physical properties of copolymers were determined by FTIR, ¹H NMR, ¹³C NMR, ³¹P NMR, and TGA. Environmental scanning electron microscopy, fluorescence spectroscopy, and dynamic light scattering method confirmed the formation of copolymeric micelles of Pluronic (F68)‐DPPE. To estimate the feasibility as novel drug carriers, the copolymer micelles were prepared by the phase separation dialysis method. Amphotericin B as a lipophilic model drug was incorporated into copolymeric micelles and the drug release behavior was investigated. It was found that the chemical composition of the micelle was a key factor in controlling micelles size, drug‐loading content, and drug release behavior. As DPPE segment weight ratio increased, the micelle size and drug‐loading content increased, and the drug release rate decreased. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Study on secondary structural transition of nano‐TiO2 modified silk fibroin composite films by two‐dimensional Raman correlation spectroscopy and solid‐state 13C‐NMR spectroscopy

By a sol–gel processing, the nano‐TiO₂/silk fibroin (SF) composite films were prepared. One‐dimensional (1D) Raman, two‐dimensional (2D) correlation Raman spectroscopy, and ¹³C cross‐polarization magic‐angle‐spinning nuclear magnetic resonance (¹³C CP‐MAS NMR) were used to characterize the structural evolution of SF as the nano‐TiO₂ content increased from 0 to 0.4 wt%. The experimental data demonstrated that the secondary structures in the pure SF film and nano‐TiO₂/silk fibroin (SF) composite films were random coil, α‐helix and β‐sheet structures. The nano‐TiO₂ particles formed in the SF films might induce partial structural transitions from random coil and Silk I (α‐helix) to Silk II (β‐sheet). The transition identified by 2D‐Raman correlation spectra was the following order: silk I‐like structure, silk I (α‐helical structure), Silk II‐like structure, and Silk II (β‐sheet structure). POLYM. COMPOS., 36:121–127, 2015. © 2014 Society of Plastics Engineers     

Highly porous starch/poly(ethylene‐alt‐maleic anhydride) composite nanofiber mesh

In this study, starch‐based hybrid electrospun nanofiber meshes were fabricated by electrospinning. Spinning solutions were prepared by mixing starch and certain amounts of poly(ethylene‐alt‐maleic anhydride). Starch‐based nanofiber meshes became insoluble in water with thermal‐induced esterification of hydroxyl groups onto starch backbone. Morphologic and structure analysis of the electrospun nanofiber meshes were investigated by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) techniques. Thermal properties of nanofiber meshes were characterized by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Thermal stability of nanofiber meshes were increased with formation of intermolecular bonds between starch and poly(ethylene‐alt‐maleic anhydride). POLYM. COMPOS. 34:1321–1324, 2013. © 2013 Society of Plastics Engineers     

Synergistic extraction of rare earths(III) from chloride medium with mixtures of 1‐phenyl‐3‐methyl‐4‐benzoyl‐pyrazalone‐5 and di‐(2‐ethylhexyl)‐2‐ethylhexylphosphonate

The synergistic effect of 1‐phenyl‐3‐methyl‐4‐benzoyl‐pyrazalone‐5 (HPMBP, HA) and di‐(2‐ethylhexyl)‐2‐ethylhexylphosphonate (DEHEHP, B) in the extraction of rare earths (RE) from chloride solutions has been investigated. Under the experimental conditions used, there was no detectable extraction when DEHEHP was used as a single extractant while the amount of RE(III) extracted by HPMBP alone was also low. But mixtures of the two extractants at a certain ratio had very high extractability for all the RE(III). For example, the synergistic enhancement coefficient was calculated to be 9.35 for Y³⁺, and taking Yb³⁺ and Y³⁺ as examples, RE³⁺ is extracted as RE(OH)A₂.B. The stoichiometry, extraction constants and thermodynamic functions such as Gibbs free energy change ΔG (?17.06 kJ mol^?1), enthalpy change ΔH (?35.08 kJ mol^?1) and entropy change ΔS (?60.47 J K^?1 mol^?1) for Y³⁺ at 298 K were determined. The separation factors (SF) for adjacent pairs of rare earths were calculated. Studies show that the binary extraction system not only enhances the extraction efficiency of RE(III) but also improves the selectivity, especially between La(III) and the other rare earth elements. Copyright © 2006 Society of Chemical Industry     

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