Epoxidized poly(N‐isopropyl acrylamide)‐b‐epoHTPB‐b‐poly(N‐isopropyl acrylamide) triblock copolymer micelle nanoparticles for 10‐hydroxycamptothecin drug release

Thermoresponsive poly(N‐isopropyl acrylamide) (PNIPAM)‐block‐hydroxy‐terminated polybutadine‐block‐PNIPAM triblock copolymers were synthesized by atom transfer radical polymerization; this was followed by the in situ epoxidation reaction of peracetic acid. The copolymers were characterized by ¹H‐NMR, Fourier transform infrared spectroscopy, and size exclusion chromatography measurements, and their physicochemical properties in aqueous solution were investigated by surface tension measurement, fluorescent spectrometry, ultraviolet–visible transmittance, transmission electron microscopy observations, dynamic light scattering, and so on. The experimental results indicate that the epoxidized copolymer micelle aggregates retained a spherical core–shell micelle structure similar to the control sample. However, they possessed a decreased critical aggregate concentration (CAC), increased hydrodynamic diameters, and a high aggregation number and cloud point because of the incorporation of epoxy groups and so on. In particular, the epoxidized copolymer micelles assumed an improved loading capacity and entrapment efficiency of the drug, a preferable drug‐release profiles without an initial burst release, and a low cytotoxicity. Therefore, they were more suitable for the loading and delivery of the hydrophobic drug as a controlled release drug carrier. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41877.     

Cephazoline sodium release from poly(N‐isopropyl acrylamide‐co‐N,N‐dimethylacrylamide) hydrogels

Hydrogels are hydrophilic polymers that swell to an equilibrium volume in the presence of water, preserving their shape. The dynamic swelling behavior of poly(N‐isopropylacrylamide‐co‐N,N‐dimethylacrylamide) [poly(NIPA‐co‐DMA)] copolymers at 37°C was investigated. It was observed that the swelling degree in the copolymers decreases with the N‐isopropylacrylamide content. In addition, the liberation mechanism was found to be Fickian. Diffusion coefficients according to Fick′s law as a function of the N‐isopropylacrylamide concentration and results of the release process are reported. The kinetics of cephazoline sodium release from poly(NIPA‐co‐DMA) hydrogels with different compositions was studied. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 91: 3433–3437, 2004     

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

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

Thermoreversible hydrogels. XIX. Synthesis and swelling behavior and drug release behavior for the N‐isopropylacrylamide/poly(ethylene glycol) methylether acrylate copolymeric hydrogels

A series of thermosensitive copolymeric hydrogels were prepared from various molar ratios of N‐isopropylacrylamide (NIPAAm) and poly(ethylene glycol) methylether acrylate (PEGMEA_n), which was synthesized from acryloyl chloride and poly(ethylene glycol) mono methylether with three oxyethylene chain lengths. Investigation of the effect of the chain length of oxyethylene in PEGMEA_n, and the amount of the PEGMEA_n in the NIPAAm/PEGMEA_n copolymeric gels, on swelling behavior in deionized water was the main purpose of this study. Results showed that the swelling ratio for the present copolymeric gels increased with increasing chain length of oxyethylene in PEGMEA_n and also increased with increase in the amount of PEGMEA_n in the copolymeric gels. However, the gel strength and effective crosslinking density of these gels decreased with increase in swelling ratio. Some kinetic parameters were also evaluated in this study. Finally, the drug release and drug delivery behavior for these gels were also assessed. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1683–1691, 2003     

Microwave‐induced enhancement of the dissolution rate of poorly water‐soluble tibolone from poly(ethylene glycol) solid dispersions

In this study, solid dispersions of poorly water‐soluble Tibolone in a poly(ethylene glycol) matrix were prepared with conventional melt mixing and microwave irradiation. The results of the assay content, LC–MS, and ¹H‐NMR indicated that microwave irradiation did not affect drug stability when a relatively low irradiation power (440 W) was used. Fourier transform infrared spectroscopy indicated that there were no hydrogen bonds formed between Tibolone and poly(ethylene glycol), and this affected the drug's crystallinity and its particle size distribution. The dissolution rate of the drug was slightly higher in the case of dispersions prepared by microwave irradiation. This enhancement of the drug dissolution rate was probably due to the lower size of the Tibolone particles in the dispersions prepared by microwave irradiation. The application of microwaves represents a promising alternative to conventional preparative methods of drug dispersions. The main advantage in comparison with conventional melt mixing is that solid dispersions can be prepared in much shorter times. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Semi‐interpenetrating networks based on poly(N‐isopropyl acrylamide) and poly(N‐vinylpyrrolidone)

Three series of novel semi‐interpenetrating polymer networks, based on crosslinked poly(N‐isopropylacrylamide), PNIPA, and different amounts of the linear poly(N‐vinylpyrrolidone), PVP, were synthesized to improve the mechanical properties and thermal response of PNIPA gels. The effect of the incorporation of the linear PVP into the temperature responsive networks on the temperature‐induced transition, swelling/deswelling behavior, and mechanical properties was studied. Polymer networks with four different crosslinking densities were prepared with varying molar ratios (25/1 to 100/1) of the monomer (N‐isopropylacrylamide) to the crosslinker (N,N′‐methylenebisacrylamide). The hydrogels were characterized by determination of the equilibrium degree of swelling, the dynamic shear modulus and the effective crosslinking density, as well as tensile strength and elongation at break. Furthermore, the deswelling kinetics of the hydrogels was studied by measuring their water retention capacity. The inclusion of the linear hydrophilic PVP in the PNIPA networks increased the equilibrium degree of swelling. The tensile strength of the semi‐interpenetrating networks (SIPNs) reinforced with linear PVP was higher than that of the PNIPA networks. The elongation at break of these SIPNs varied between 22% and 55%, which are 22 – 41% larger than those for pure PNIPA networks. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation and characterization of pH responsive poly(methacrylic acid‐acrylamide‐N‐hydroxyethyl acrylamide) hydrogels for drug delivery systems

In this study, pH responsive polymers composed of methacrylic acid, acrylamide, and N‐hydroxyethyl acrylamide were synthesized by free radical polymerization technique. The characterization was done with Fourier transform infrared spectroscopy and scanning electron microscopy. The swelling and drug release behavior of the hydrogels was determined as a function of time at 37°C in pH 2.1 and 7.4. The swelling and drug release studies showed that increased methacrylic acid amount caused a higher increase in swelling and drug release values at pH 7.4 than those at pH 2.1. In addition, the drug release data were applied to kinetic models such as zero order, first order, and Higuchi equations, and it fit well in the Higuchi model of the hydrogel. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43226.     

Preparation and evaluation of radioiodinated thermoresponsive polymer based on poly(N‐isopropyl acrylamide) for radiotherapy

A thermoresponsive polymer based on poly N‐isopropylacrylamide (PNIPAM) was synthesized and radioiodinated to explore its potential use in localized radiotherapy. The synthesized PNIPAM polymer was functionalized with L ‐tyrosinamide to facilitate radioiodination. The content of tyrosinamide groups in the polymer was assayed spectrophotometrically (λ = 275nm). The functionalized polymer showed a cloud point temperature of 29–31°C and phase separation at 35°C, as revealed by Differential Scanning Calorimetry (DSC) and Dynamic Light Scattering (DLS). The phase transition temperature is conducive for preferential localization of the polymer at the site of injection due to changes in the polymer conformation at body temperature. For in vivo demonstration, the biodistribution studies of radioiodinated polymer were carried out in Swiss mice bearing fibrosarcoma tumor. Biodistribution studies showed a retention of 30% of the injected labeled polymer, PNIPAM‐¹²⁵I‐tyrosinamide, in the solid tumor tissues after 2 h of intratumoral injection. Although the activity decreased with time, 3–4% of the injected dose (i.d) was found to be retained in the tumor on 5 d post injection. The results suggest the potential use of thermosensitive polymer based on poly N‐isopropylacrylamide for locoregional radionuclide therapy. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 860‐868, 2013     

Preparation and microstructural analysis of poly(ethylene oxide) comb‐type grafted poly(N‐isopropyl acrylamide) hydrogels crosslinked by poly(ϵ‐caprolactone)

Poly(N‐isopropyl acrylamide) (PNIPAAm)‐graft‐poly(ethylene oxide) (PEO) hydrogels crosslinked by poly(?‐caprolactone) diacrylate were prepared, and their microstructures were investigated. The swelling/deswelling kinetics and compression strength were measured. The relationship between the structure and properties of hydrogel are discussed. It was found that the PEO comb‐type grafted structure reduced the thermosensitivity and increased the compression strength. The addition of poly(?‐caprolactone) (PCL) accelerated the deswelling rate of the hydrogels. Meanwhile, the entanglement of PCL chains restrained the further swelling of the network of gels. The PCL crosslinking agent and PEO comb‐type grafted structure made the behavior of the hydrogels deviate from the rubber elasticity equations. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Molecular interactions in poly(methacrylic acid)/poly(N‐isopropyl acrylamide) interpenetrating polymer networks

The molecular interactions between the component networks in poly(methacrylic acid)/poly(N‐isopropyl acrylamide) (PMAA/PNIPAAm) interpenetrating polymer networks (IPNs) were investigated using attenuated total reflectance (ATR)‐Fourier transform IR (FTIR) spectroscopy. Hydrogen‐bond formation was noted between the carboxyl groups of PMAA and the amide groups of PNIPAAm. The ATR‐FTIR results showed shifts in the carboxylic and amide groups, indicating the existence of hydrogen bonding between these two individual networks within the IPNs. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 1077–1082, 2001     

Mechanical properties of poly(N‐isopropyl‐acrylamide‐co‐itaconic acid) hydrogels

Hydrogels of N‐isopropylacrylamide and itaconic acid were synthesized with different monomer ratios and with two crosslinking agent concentrations. The different xerogels were immersed in water and the swelling process was conducted up to equilibrium conditions at two temperatures (22 and 37°C). These temperatures are lower and higher than the transition temperature shown by PNIPA hydrogels. The mechanical properties of the different solvated hydrogels were examined by oscillatory shear measurements at 22 and 37°C. The copolymer volume fraction and the elastic storage modulus of the hydrogels decreased as the itaconic acid percentage in the copolymer increased. This behavior was attributed to the higher hydrophilic character of the itaconic acid comonomer. Effective crosslinking density, molar mass between crosslinks, and the polymer–solvent interaction parameter were determined from the experimental values of the elastic storage moduli and the copolymer volume fractions. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2540–2545, 2002     

Improved swelling–deswelling behavior of poly(N‐isopropyl acrylamide) gels with poly(N,N′‐dimethyl aminoethyl methacrylate) grafts

Thermoresponsive and pH‐responsive gels were synthesized from N‐isopropyl acrylamide (NIPA) and N,N′‐dimethyl aminoethyl methacrylate (DMAEMA) monomers. Gelation reactions were carried out with both conventional free‐radical polymerization (CFRP) and controlled free‐radical polymerization [reversible addition fragmentation transfer (RAFT)] techniques. The CFRP gels were prepared by polymerizing mixtures of NIPA and DMAEMA in 1,4‐dioxane in presence of N,N'‐methylene bisacrylamide (BIS) as cross‐linker. The RAFT gels were prepared by a the polymerization of NIPA via a similar process in the presence of different amounts of poly(N,N′‐dimethyl aminoethyl methacrylate) macro chain‐transfer agent and the crosslinker. These gels were characterized by scanning electron microscopy (SEM) and differential scanning calorimetry. SEM analysis revealed a macroporous network structure for the RAFT gels, whereas their volume phase‐transition temperatures (VPTTs) were found to be in the range 32–34°C, close to that of poly(N‐isopropyl acrylamide) gels. However, the CFRP copolymer gels exhibited a higher VPTT; this increased with increasing DMAEMA content. The RAFT gels exhibited higher swelling capabilities than the corresponding CFRP gels and also showed faster shrinking–reswelling behavior in response to changes in temperature. All of the gels showed interesting pH‐responsive behavior as well. The unique structural attributes exhibited by the RAFT gels can potentially open up opportunities for developing new materials for various applications, for example, as adsorbents or carrier of drugs or biomolecules. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42749.     

Synthesis and characterization of a novel stimuli‐responsive magnetite nanohydrogel based on poly(ethylene glycol) and poly(N‐isopropylacrylamide) as drug carrier

A novel stimuli‐responsive magnetite nanohydrogel (MNHG), namely [poly(ethylene glycol)‐block‐poly(N‐isopropylacrylamide‐co‐maleic anhydride)₂]‐graft‐poly(ethylene glycol)/Fe₃O₄ [PEG‐b‐(PNIPAAm‐co‐PMA)₂]‐g‐PEG/Fe₃O₄, was successfully developed. For this purpose, NIPAAm and MA monomers were block copolymerized onto PEG‐based macroinitiator through atom transfer radical polymerization technique to produce PEG‐b‐(PNIPAAm‐co‐PMA)₂. The synthesized Y‐shaped terpolymer was crosslinked through the esterification of maleic anhydride units using PEG chains to afford a hydrogel. Afterward, magnetite nanoparticles were incorporated into the synthesized hydrogel through the physical interactions. The chemical structures of all synthesized samples were characterized using Fourier transform infrared and proton nuclear magnetic resonance spectroscopies. Morphology, thermal stability, size, and magnetic properties of the synthesized MNHG were investigated. In addition, the doxorubicin hydrochloride loading and encapsulation efficiencies as well as stimuli‐responsive drug release ability of the synthesized MNHG were also evaluated. The drug‐loaded MNHG at physiological condition exhibited negligible drug release values. In contrast, at acidic (pH 5.3) condition and a little bit higher temperature (41 °C) the developed MNHG showed higher drug release values, which qualified it for cancer chemotherapy due to especial physiology of cancerous tissue in comparison with the surrounding normal tissue. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46657.     

Effect of intercalant content of mica on the various properties for the charged nanocomposite poly(N‐isopropyl acrylamide) hydrogels

In this study, we intend to adjust the charge properties of the poly(N‐isopropylacrylamide) [Poly(NIPAAm)] gel by using anionic clay and cationic monomer. Hence, two series of nanocomposite hydrogels bearing different charges were designed from NIPAAm, intercalated mica (IM) (NIM‐series) and NIPAAm, IM, trimethyl (acrylamido propyl) ammonium iodide (TMAAI) (NTIM‐series), respectively. The mica was first intercalated with different contents of intercalant, trimethyl (acrylamido propyl) ammonium chloride (TMAACl), based on the cationic exchange capacity (CEC) of mica. The effect of the CEC value of IM and IM content on the charge property, swelling behaviors, mechanical properties, and drug‐release behaviors of the present gels were investigated. Results showed that the negative charges for NIM series gels decrease with increase in CEC values of the IM (from ?11 to ?6 mV), the positive charges for NTIM series gels also decrease with increase in CEC values of the IM (from +36 to +18 mV). The swelling behaviors and mechanical properties for the NTIM gels were significantly enhanced by IM content and CEC values of the IM. The microstructures, morphologies, and drug‐release behaviors in these two series gels are also investigated. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 2277–2287, 2007     

Physicochemical characterization of poly(ethylene glycol) plasticized poly(methyl vinyl ether‐co‐maleic acid) films

The influence of the poly(ethylene glycol) (PEG) plasticizer content and molecular weight on the physicochemical properties of films cast from aqueous blends of poly(methyl vinyl ether‐co‐maleic acid) (PMVE/MA) was investigated with tensile mechanical testing, thermal analysis, and attenuated total reflectance/Fourier transform infrared spectroscopy. Unplasticized films and those containing high copolymer contents were very difficult to handle and proved difficult to test. PEG with a molecular weight of 200 Da was the most efficient plasticizer. However, films cast from aqueous blends containing 10% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000 when the copolymer/plasticizer ratio was 4 : 3 and those cast from aqueous blends containing 15% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000 when the copolymer/plasticizer ratio was 2 : 1 possessed mechanical properties most closely mimicking those of a formulation we have used clinically in photodynamic therapy. Importantly, we found previously that films cast from aqueous blends containing 10% (w/w) PMVE/MA performed rather poorly in the clinical setting, where uptake of moisture from patients' skin led to reversion of the formulation to a thick gel. Consequently, we are now investigating films cast from aqueous blends containing 15% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000, where the copolymer/plasticizer ratio is 2 : 1, as possible Food and Drug Administration approved replacements for our current formulation, which must currently be used only on a named patient basis as its plasticizer, tripropylene glycol methyl ether, is not currently available in pharmaceutical grade. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Synthesis and characterization of novel pH‐responsive poly(2‐hydroxylethyl methacrylate‐co‐N‐allylsuccinamic acid) hydrogels for drug delivery

In this study, N‐allylsuccinamic acid (NASA) was synthesized in a single step with a yield of 85%. Carboxylic acid containing NASA was characterized through Fourier transform infrared (FTIR) radiation and ¹H‐NMR and ¹³C‐NMR analysis, and then it was used for synthesis of poly(2‐hydroxylethyl methacrylate‐co‐N‐allylsuccinamic acid) [p(HEMA‐co‐NASA)] hydrogels. The structure of the obtained pH‐responsive p(HEMA‐co‐NASA) hydrogels were characterized with FTIR spectroscopy and scanning electron microscopy analysis, and their swelling characterization was carried out under different drug‐release conditions. In the application step of the study, the hydrogels were used for the in vitro release of vitamin B12 and Rhodamine 6G, which were selected as model drugs. We determined that the hydrogels used as a drug‐delivery matrix could release the drug they had absorbed under different release conditions (phosphate‐buffered saline, 0.9% NaCl, and pH 1.2) at high rates for time periods of up to 24 h. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39660.     

Thermoreversible hydrogel. XVII. Investigation of the drug release behavior for [N‐isopropylacrylamide‐co‐trimethyl acrylamidopropyl ammonium iodide‐co‐3‐dimethyl (methacryloyloxyethyl) ammonium propane sulfonate] copolymeric hydrogels

A series of copolymeric hydrogels were prepared from various molar ratios of N‐isopropylacrylamide (NIPAAm), trimethyl acrylamidopropyl ammonium iodide (TMAAI), and 3‐dimethyl (methacryloyloxyethyl) ammonium propane sulfonate (DMAPS). Results showed that the swelling ratios of these copolymeric hydrogels increased with an increase of TMAAI content. The drug release behavior of the ionic thermosensitive hydrogels related to their ionicity and drug types. Results indicated that the release ratio of caffeine in the hydrogels was not affected by the ionicity of hydrogels, but increased with increasing of the swelling ratio. The anionic solute (phenol red) strongly interacted with cationic hydrogel (very large K_d), so the phenol red release ratio in cationic gels was very low. On the other hand, CV was adsorbed only on the skin layer of the cationic hydrogel because of the charge repulsion, and released rapidly. Therefore the release ratio was highest for cationic hydrogel to cationic drug. In addition, the partition coefficients (K_d) and the drug delivery behavior of the present gels were also investigated. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1592–1598, 2002     

Thermosensitive polymeric micelles based on the triblock copolymer poly(d,l‐lactide)‐b‐poly(N‐isopropyl acrylamide)‐b‐poly(d,l‐lactide) for controllable drug delivery

A thermosensitive amphiphilic triblock copolymer, poly(d,l ‐lactide) (PLA)‐b‐poly(N‐isopropyl acrylamide) (PNIPAAM)‐b‐PLA, was synthesized by the ring‐opening polymerization of d,l ‐lactide; the reaction was initiated from a dihydroxy‐terminated poly(N‐isopropyl acrylamide) homopolymer (HO‐PNIPAAM‐OH) created by radical polymerization. The molecular structure, thermosensitive characteristics, and micellization behavior of the obtained triblock copolymer were characterized with Fourier transform infrared spectroscopy, ¹H‐NMR, gel permeation chromatography, dynamic light scattering, and transmission electron microscopy. The obtained results indicate that the composition of PLA‐b‐PNIPAAM‐b‐PLA was in good agreement with what was preconceived. This copolymer could self‐assemble into spherical core–shell micelles (ca. 75–80 nm) in aqueous solution and exhibited a phase‐transition temperature around 26 °C. Furthermore, the drug‐delivery properties of the PLA‐b‐PNIPAAM‐b‐PLA micelles were investigated. The drug‐release test indicated that the synthesized PLA‐b‐PNIPAAM‐b‐PLA micelles could be used as nanocarriers of the anticancer drug adriamycin (ADR) to effectively control the release of the drug. The drug‐delivery properties of PLA‐b‐PNIPAAM‐b‐PLA showed obvious thermosensitive characteristics, and the release time of ADR could be extended to 50 h. This represents a significant improvement from previous PNIPAAM‐based drug‐delivery systems. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45304.     

Poly[(N‐isopropylacrylamide)‐co‐(itaconic acid)] hydrogels with poly(ethylene glycol)

The aim of the work reported here was to investigate temperature‐ and pH‐sensitive hydrogels of N‐isopropylacrylamide (NIPAM) and itaconic acid (IA) and their semi‐interpenetrating polymer networks (semi‐IPNs) with varying contents of poly(ethylene glycol) (PEG). The stimuli responsiveness, swelling behaviour and mechanical properties of the hydrogels and semi‐IPNs were studied in order to investigate the effect of various amounts of PEG. Pulsed‐gradient spin‐echo NMR experiments were carried out to investigate the diffusion process. The pH sensitivity increased with an increasing amount of PEG in the semi‐IPNs, while the overall rate of water uptake was diffusion‐controlled (n < 0.5). For certain PEG contents (5 and 10 wt%), the semi‐IPNs exhibited better mechanical properties than the poly(NIPAM‐co‐IA) copolymer. The calculated values of the self‐diffusion coefficients of water indicated facilitated diffusion of water through the system with increased amounts of PEG, while the self‐diffusion coefficients of a model compound, metoprolol tartrate, showed no significant dependence on the amount of PEG. According to the results obtained and compared to results reported in the literature, the investigated semi‐IPNs may have potential applications in the controlled release of macromolecular active agents such as proteins and peptides. Copyright © 2009 Society of Chemical Industry     

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

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