Embedded of Nanogel into Multi-responsive Hydrogel Nanocomposite for Anticancer Drug Delivery

Hydrogels, nanogels, and nanocomposites show increasing potential for application in drug delivery systems due to their good chemical and physical properties. Therefore, we were encouraged to combine them to produce a new compound with unique properties for drug release systems. To this aim, we first prepared poly [(N-isopropylacrylamide)-co-(2-dimethylamino ethyl methacrylate) nanogel by copolymerization processes and then added it into the solution of poly (2-dimethylamino ethyl methacrylate)] grafted onto salep. Through dropwise addition of mixed aqueous solution of iron salts into the prepared polymeric solution, a novel hydrogel nanocomposite with excellent pH, thermo, and magnetic responsive was fabricated. The obtained hydrogel nanocomposite were characterized by Fourier transform infrared spectroscopy, thermo gravimetric analysis, X-ray diffraction, scanning electron microscopy, vibrating sample magnetometer, and atomic force micrographs. The dependence of swelling properties of hydrogel nanocomposite on the temperature, pH, and magnetic field were investigated. The release behavior of doxorubicin hydrochloride (DOX) drug from DOX loaded into synthesized hydrogel nanocomposite was investigated at different pHs, temperatures, and magnetic field. In addition, the drug release behavior from obtained hydrogel nanocomposite was monitored via different kinetic models. Lastly, the toxicity of the DOX and DOX-loaded hydrogel nanocomposite were studied on MCF-7 cells at different times. These results suggested that the obtained hydrogel nanocomposite might have high potential applications in drug delivery systems.     

Near‐Infrared Light‐Triggered Dual Drug Release Using Gold Nanorod‐Embedded Thermosensitive Nanogel‐Crosslinked Hydrogels

Gold nanorod (AuNR)‐embedded poly(N‐isopropylacrylamide) (PNIPAM) hydrogels offer the possibility of achieving near‐infrared (NIR) light‐triggered drug release. In addition, using nanoparticles as a crosslinker can enhance the mechanical properties of PNIPAM hydrogels, and nanoparticle‐crosslinked hydrogels provide an important approach for dual drug release. Here, NIR light‐triggered dual drug release using AuNR‐embedded thermosensitive nanogel‐crosslinked hydrogels is reported for the first time. Two kinds of drugs are encapsulated, one in the nanogel and the other in the hydrogel. The volume phase transition of the PNIPAM hydrogels is induced by NIR light by utilizing the photothermal effect of AuNRs. By changing the number of embedded AuNRs and the intensity of NIR light, the release rate and drug quantity can be adjusted for on‐demand release. Because of its NIR light‐triggering and nanoparticle‐crosslinking capabilities, AuNR‐embedded thermosensitive nanogel‐crosslinked hydrogels may expand the application scope of hydrogels and provide enhanced properties in their applications.     

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 an alginate–poly(sodium acrylate‐co‐acrylamide) superabsorbent hydrogel with low salt sensitivity and high pH sensitivity

This article describes the synthesis and swelling behavior of a superabsorbing hydrogel based on sodium alginate (NaAlg) and polyacrylonitrile (PAN). The physical mixture of NaAlg and PAN was hydrolyzed with a solution of NaOH to yield an alginate–poly(sodium acrylate‐co‐acrylamide) [Alg–poly(NaAA‐co‐AAm)] superabsorbent hydrogel. A proposed mechanism for hydrogel formation was suggested, and the structure of the product was established with Fourier transform infrared spectroscopy. The effects of reaction variables were systematically optimized to achieve a hydrogel with a swelling capacity as high as possible. Under the optimized conditions concluded, the maximum capacity of swelling in distilled water was 610 g/g. The absorbency of the synthesized hydrogels was also measured in various salt solutions. The swelling ratios decreased with an increase in the ionic strength of the salt solutions. In addition, the swelling capacity was determined in solutions with pHs ranging from 1 to 13. The Alg–poly(NaAA‐co‐AAm) hydrogel exhibited pH responsiveness, so a swelling–deswelling pulsatile behavior was recorded at pHs 2 and 8. This on–off switching behavior made the hydrogel as a good candidate for the controlled delivery of bioactive agents. Finally, the swelling kinetics of the hydrogels with various particle sizes were preliminarily investigated as well. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2927–2937, 2006     

A thermo/pH/magnetic-responsive nanogel based on sodium alginate by modifying magnetic graphene oxide: Preparation,characterization, and drug delivery

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

Imaging‐Guided pHe and Glutathione Dual Responsive Polypeptide Nanogel for Smart Drug Delivery

A negatively charged polypeptide nanogel, near‐infrared (NIR) cyanine dye (Cy5.5) conjugated and 2,3‐dimethylmaleic anhydride (DMA) modified poly‐l ‐lysine‐co‐l ‐cystine (CDPLC), is synthesized and is used as an imaging‐guided sequential drug delivery system. The CDPLC nanogel can respond to two general stimulations in sequence: extracellular tumor acidic microenvironment pHe (6.8–6.5) and intracellular high concentration glutathione (GSH). Under pHe, the DMA shell of the nanogel is removed and a charge reversal takes place, resulting in positively charged nanogel which can be internalized by cancer cells easily. Once internalized into tumor cells, the increased intracellular GSH concentration further promotes DOX release from the nanogel and DOX is enriched to the nucleus. Cy5.5 is conjugated to the nanogel as an NIR fluorescent probe, making it possible for imaging‐guided drug delivery, which is confirmed by the MTT and confocal laser scanning microscopy via in vitro experiments. The as‐prepared nanogel is a potential theranostic for cancer therapy.     

Gum Acacia‐cl‐poly(acrylamide)@carbon nitride Nanocomposite Hydrogel for Adsorption of Ciprofloxacin and its Sustained Release in Artificial Ocular Solution

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

Graphene Oxide Hybrid Supramolecular Hydrogels with Self‐Healable,Bioadhesive and Stimuli‐Responsive Properties and Drug Delivery Application

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

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     

Poly(N‐isopropylacrylamide) hydrogel: Effect of hydrophilicity on controlled release of ibuprofen at different pH

Stimuli‐sensitive drug delivery systems (DDSs) have attracted considerable attention in medical and pharmaceutical fields; thermo‐sensitive DDS dealing with poly(N‐isopropylacrylamide) (PNIPAM) have been widely studied. Hydrogels composed of temperature‐sensitive NIPAM and biocompatible and pH‐sensitive maleic acid (MAc) were synthesized by sedimentation polymerization. Experiments on drug release from the crosslinked NIPAM‐co‐MAc hydrogel loaded with ibuprofen into different pH buffer solutions were successfully carried out at temperature swing between 25 and 40°C. The in vitro release studies have showed that the release rate depended on acidity or basicity (polarity) of the medium and the gel and swelling ratio of the gel network as a function of the environmental pH and temperature. The SEM image of the dry bead gave more insight into the surface architecture and the thermal studies shine light on the decomposition pattern and glass transition temperature of the gel. The mechanism of the drug release was discussed in relation to the diffusion rate and the abrupt change in the pH of the medium. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Graphene oxide/poly(<Emphasis Type="Italic">N</Emphasis>-isopropyl acrylamide)/sodium alginate-based dual responsive composite beads for controlled release characteristics of chemotherapeutic agent

In this work, graphene oxide (GO)-incorporated composite beads were developed from poly(N-isopropyl acrylamide)/sodium alginate (PNIPAM/NaAlg) using ionotropic gelation technique. The interaction between GO and PNIPAM/NaAlg with Ca²⁺ ions as a cross-linker was investigated by Fourier transform spectroscopy. X-Ray diffraction pattern showed that the GO was distributed uniformly in the PNIPAM/NaAlg with Ca²⁺ ions while scanning electron micrograph technique revealed that composite beads were formed in spherical shape. The controlled release characteristics of composite beads were studied using 5-fluorouracil (5-FU) as anti-cancer model drug. The encapsulation efficiencies were found to be between 90 and 92% in all formulations. Furthermore, the equilibrium swelling ratio (%) and in vitro release studies of the beads were carried out in two different pH values of 1.2 and 7.4 and at different temperature conditions of 25 and 37 °C. The obtained results showed that the swelling ratio decreased with an increase in GO concentration. In vitro release studies performed in response to both pH and temperature and they proved that the 5-FU drug was released from composite beads over 32 h without burst release. Cytotoxicity results showed pristine composite beads are good cytocompatible. In addition, the cytotoxicity of 5-FU was found to be improved when incorporated with composite beads than pure 5-FU. It is therefore concluded that the developed composite beads have dual response and can be used as controlling released carriers in cancer drug delivery applications.     

Magnetic and electric responsive hydrogel–magnetic nanocomposites for drug‐delivery application

Magnetic and electrically responsive hydrogel networks were developed for drug‐delivery applications. The hydrogel matrices were synthesized by the polymerization of acrylamide monomer in the presence of carboxymethylcellulose (CMC) or methylcellulose (MC) with N,N‐methylenebisacrylamide, a crosslinker with the redox initiating system ammonium persulfate/tetramethylethylenediamine. The magnetic nanoparticles were generated throughout these hydrogel matrices by an in situ method by the incorporation of iron ions and their subsequent reduction with ammonia. A series of hydrogel–magnetic nanocomposites (HGMNCs) were developed with various CMC and MC compositions. The synthesized HGMNCs were characterized with spectral (Fourier transform infrared and ultraviolet–visible spectroscopy), X‐ray diffraction, thermal, and microscopy methods. These HGMNCs contained iron oxide (Fe₃O₄) nanoparticles with an average particle size of about 22 nm, as observed by transmission electron microscopy. The dielectrical properties of the pure hydrogel (HG); the hydrogel loaded with iron ions, or the hydrogel iron‐ion composite (HGIC); and the HGMNCs were measured. These results suggest that HGMNCs exhibited higher dielectric constants compared to HG and HGICs. The curcumin loading and release characteristics were also measured for HG, HGIC, and HGMNC systems. These data revealed that there was a sustained release of curcumin from HGMNCs because of the presence of magnetic nanoparticles in the hydrogel networks. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Preparation and characterization of poly(N‐tert‐butylacrylamide‐co‐acrylamide) ferrogel

Magnetic‐field‐sensitive gel, called ferrogel, was prepared by a two‐step procedure in which first step requires synthesis of the poly(N‐tert‐butylacrylamide‐co‐acrylamide) [P(NTBA‐co‐AAm)] hydrogel and during second step magnetite (Fe₃O₄) particles were formed in the hydrogel via coprecipitation of Fe(II) and Fe(III) ions in alkaline medium at 70°C. The obtained ferrogel was characterized by attenuated total reflectance Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy combined with energy dispersive spectroscopy, and electron spin resonance measurements. The magnetic responsive of the ferrogel was also investigated by applying magnetic field to the ferrogel. The extent of a bending degree of the ferrogel depends on the applied magnetic field strength. In addition, the magnetic responsive studies also indicated that formed magnetite content in the hydrogel is high enough to achieve considerable magnetic response to external magnetic field. As a result, the P(NTBA‐co‐AAm) ferrogel may be useful for potential applications in magnetically controlled drug release systems, magnetic‐sensitive sensors, and pseudomuscular actuators. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Thermal and pH dual‐responsive hydrogels based on semi‐interpenetrating network of poly(N‐isopropylacrylamide) and collagen nanofibrils

Hydrogels with environment‐sensitive properties have great potential applications in the controlled drug release field. In this paper, hybrid hydrogels with semi‐interpenetrating polymer networks (semi‐IPNs), composed of poly(N‐isopropylacrylamide) (PNIPAM) as the thermo‐sensitive component by in situ polymerization and self‐assembled collagen nanofibrils as the pH‐sensitive framework, were prepared for controlled release of methyl violet as a model drug. From Fourier transform infrared spectroscopy and scanning electron microscopy, it was indicated that the crosslinking of PNIPAM in the presence of collagen nanofibrils led to the formation of semi‐IPNs with homogeneous porous structure, and the semi‐IPNs showed improved thermal stability and elastic properties compared with the native collagen as determined using differential scanning calorimetry and rheologic measurements. Furthermore, the semi‐IPNs possessed swelling behaviors quite different from those of neat collagen or PNIPAM hydrogel under various pH values and temperatures. Correspondingly, as expected, the drug release behavior in vitro for semi‐IPNs performed variously compared with that for single‐component semi‐IPNs, which revealed the tunable performance of semi‐IPNs for release ability. Finally the thermo‐ and pH‐responsive mechanism of the semi‐IPNs was illuminated to provide guidance for the application of the thermo‐ and pH‐sensitive collagen‐based hybrid hydrogels in controlled drug delivery systems. © 2019 Society of Chemical Industry     

Synthesis and characterization of poly(N‐vinyl‐2‐pyrrolidone) grafted sodium alginate hydrogel beads for the controlled release of indomethacin

Graft copolymers of sodium alginate (NaAlg) with N‐vinyl‐2‐pyrrolidone were prepared using azobisisobutyronitrile as initiator. The graft copolymers (NaAlg‐g‐PVP) were characterized with Fourier transform infrared spectroscopy, elemental analysis, and differential scanning calorimetry. Polymeric hydrogel beads of NaAlg and NaAlg‐g‐PVP were prepared by crosslinking method using glutaraldehyde (GA) as a crosslinker in the hydrochloric acid catalyst (HCl) and these beads were used to deliver anti‐inflammatory drug, indomethacin (IM). Chemical stability of the IM after encapsulation into beads was confirmed by FTIR. Preparation conditions of the NaAlg‐g‐PVP beads were optimized by considering the percentage entrapment efficiency, particle size, swelling capacity and their release data. In vitro release studies were performed in simulated gastric fluid (pH 1.2) for the initial 2 h, followed by simulated intestinal fluid (pH 7.4) for 4 h. Effects of GA concentration, exposure time to GA, drug/polymer (d/p) ratio, and concentration of HCl on the release of IM were discussed. It was observed that IM release from the beads decreased with increasing GA concentration and exposure time. IM release also decreases with increasing d/p ratio and HCl concentration. The highest IM release was obtained to be 77% for beads crosslinked with 0.027M GA. Swelling experiments were also performed to compute molecular mass between crosslinks of the beads. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

A Composite Thermo‐Responsive Membrane System for Improved Controlled‐Release

A novel composite thermo‐responsive membrane system for improved controlled‐release is successfully developed. The membrane is composed of a porous membrane with grafted poly(N‐isopropylacrylamide) (PNIPAM) gates acting as functional valves, and a cross‐linked PNIPAM hydrogel inside the reservoir acting as the solute carrier. The thermo‐responsive controlled‐release characteristics of the proposed system are studied when the ambient temperature is continuously increased from 20 to 45 °C (across the LCST of PNIPAM) at a constant rate of 1.5 °C/min. The experimental results show that the prepared system exhibits significantly better performance for thermo‐responsive controlled‐release than single‐functional systems currently in existence, due to the cooperative action of the gating membrane and the inner cross‐linked hydrogel. Furthermore, due to the distinctive composite architecture, the proposed system can overcome some inherent disadvantages of current systems, such as the drug security problem of the reservoir‐type systems and the mechanical strength problem of the hydrogel matrix‐type systems. The system proposed in this study provides a new mode for thermo‐responsive controlled‐release.     

Temperature,pH, and reduction triple‐stimuli‐responsive inner‐layer crosslinked micelles as nanocarriers for controlled release

Temperature, pH, and reduction triple‐stimuli‐responsive inner‐layer crosslinked micelles as nanocarriers for drug delivery and release are designed. The well‐defined tetrablock copolymer poly(polyethylene glycol methacrylate)–poly[2‐(dimethylamino) ethyl methacrylate]–poly(N‐isopropylacrylamide)–poly(methylacrylic acid) (PPEGMA‐PDMAEMA‐PNIPAM‐PMAA) is synthesized via atom transfer radical polymerization, click chemistry, and esterolysis reaction. The tetrablock copolymer self‐assembles into noncrosslinked micelles in acidic aqueous solution. The core‐crosslinked micelles, shell‐crosslinked micelles, and shell–core dilayer‐crosslinked micelles are prepared via quaternization reaction or carbodiimide chemistry reaction. The crosslinked micelles are used as drug carriers to load doxorubicin (DOX), and the drug encapsulation efficiency with 20% feed ratio reached 59.2%, 73.1%, and 86.1%, respectively. The cumulative release rate of DOX is accelerated by single or combined stimulations. The MTT (3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay verifies that the inner‐layer crosslinked micelles show excellent cytocompatibility, and DOX‐loaded micelles exhibit significantly higher inhibition for HepG2 cell proliferation. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46714.     

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.     

Colon‐specific oral delivery of vitamin B2 from poly(acrylamide‐co‐maleic acid) hydrogels: An in vitro study

Hydrogels, composed of poly(acrylamide‐co‐maleic acid) were synthesized and the release of vitamin B₂ from these gels was studied as a function of the pH of the external media, the initial amount of the drug loaded, and the crosslinking ratio in the polymer matrix. The gels containing 3.8 mg of the drug per gram gel exhibit almost zero‐order release behavior in the external media of pH 7.4 over the time interval of more than their half‐life period (t_1/2). The amount of the drug loaded into the hydrogel also affected the dynamic release of the encapsulated drug. As expected, the gels showed a complete swelling‐dependent mechanism, which was further supported by the similar morphology of the swelling and release profiles of the drug‐loaded sample. The hydrophilic nature of the drug riboflavin does not contribute toward the zero‐order release dynamics of the hydrogel system. On the other hand, the swelling osmotic pressure developed between the gels and the external phase, due to loading of the drug by equilibration of the gels in the alkaline drug solution, plays an effective role in governing the swelling and release profiles. Finally, the minimum release of the drug in the swelling media of pH 2.0 and the maximum release with zero‐order kinetics in the medium of pH 7.4 suggest that the proposed drug‐delivery devices have a significant potential to be used as an oral drug‐delivery system for colon‐specific delivery along the gastrointestinal (GI) tract. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 1133–1145, 2002; DOI 10.1002/app.10402     

Isothermal kinetics of (E)‐4‐(4‐metoxyphenyl)‐4‐oxo‐2‐butenoic acid release from a poly(acrylic acid‐co‐methacrylic acid) hydrogel

A kinetic study of the release of the drug (E)‐4‐(4‐metoxyphenyl)‐4‐oxo‐2‐butenoic acid (MEPBA) from a poly(acrylic acid‐co‐methacrylic acid) (PAA‐co‐MA) hydrogel was performed. The isothermal kinetic curves of MEPBA release from the PAA‐co‐MA hydrogel in bidistilled water at different temperatures ranging from 20 to 40°C were determined. The reaction rate constants of the investigated process were determined with the initial rate, the saturation rate, and Peppas's semiempirical equation. Also, a model‐fitting method for the determination of the kinetics model of drug release was applied. The influence of α at the values of the kinetic parameters and the presence of a compensation effect was established. A procedure for the determination of the distribution function of the activation energies was developed. This procedure was based on the experimentally determined relationship between the activation energy and α. The mechanism of active compound release is discussed. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008