Composites of polymeric gels and magnetic nanoparticles: Preparation and drug release behavior

The article is concerned with the preparation of polymer–iron oxide nanocomposites and the study as drug‐delivery matrices under the influence of applied magnetic field. Biocompatible materials were prepared by incorporating an aqueous ferrofluid in poly(vinyl alcohol) and scleroglucan (SCL) hydrogels, loaded with theophylline as model drug for release studies. The in vitro release profile was obtained using a flat Franz cell and the kinetic parameters were derived applying a semiempirical power law. A magnetic characterization of nanoparticles contained in the ferrofluid was performed by obtaining the magnetization curve. For both systems, the observed drug release profiles decreased when a uniform external magnetic field is applied suggesting they can be used as environmental responsive matrices for biomedical applications. Dynamic rheological measurements show that a higher storage modulus and a more compact structure are obtained by incorporating the ferrofluid into the hydrogels. These rheological results and environmental electron scanning microscopy micrographs point to an understanding of release behavior once the magnetic field is applied. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

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

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

Preparation and characterization of a positive thermoresponsive hydrogel for drug loading and release

A positive thermoresponsive hydrogel composed of poly(acrylic acid)‐graft‐β‐cyclodextrin (PAAc‐g‐β‐CD) and polyacrylamide (PAAm) was synthesized with the sequential interpenetrating polymer network (IPN) method for the purpose of improving its loading and release of drugs. The structure and properties of the PAAc‐g‐β‐CD/PAAm hydrogel (IPN hydrogel) were characterized with Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and swelling measurements. FTIR studies showed that the IPN hydrogel was primarily composed of an IPN of PAAc‐g‐β‐CD and PAAm. The data from DSC and swelling measurements indicated that the phase‐transition temperature or upper critical solution temperature (UCST) of the IPN hydrogel was approximately 35°C. Through the measurement of the temperature dependence of the swelling, increases in the UCST and non‐sensitivity to changes in the salt concentration were observed for the IPN hydrogel versus the normal IPN hydrogel poly(acrylic acid)/PAAm (without β‐cyclodextrin). Furthermore, the swelling/deswelling kinetics of the IPN hydrogel also exhibited an improved controllable response rate versus the normal IPN hydrogel. Ibuprofen (IBU) was chosen as the model drug for examining loading and release from the IPN hydrogel. The experimental data proved that the IPN hydrogel provided a positive drug release pattern; the IBU released faster at 37°C than at 25°C, and improved drug loading and controlled release were achieved by the IPN hydrogel versus the normal IPN hydrogel. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Layer‐by‐layer assembly of poly(allylamine hydrochloride)/polyurethane and its loading and release behavior for methylene orange

Here, layer‐by‐layer technique was used for sequential adsorption of oppositely charged polymer poly(allylamine hydrochloride) (PAH) and polyurethane (PU) through electrostatic interaction. 10 and 10.5 bilayer films were prepared separately, methylene orange (MO) was used as a model drug to evaluate the potential ability of this multilayer film used in drug delivery system. Experimental results showed the ability of loading and release of MO from the film was significantly influenced by pH and salt concentration, the loading rate of MO was faster and larger with increasing salt concentration or decreasing pH of MO solution, the release rate of MO was faster at higher salt concentration or in alkali solution. The result also indicated that the film had a good reversibility of loading and release. PAH/PU film could be a promising drug delivery system because of its biocompatibility, biodegradation and above properties. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Thermoresponsive/low‐fouling Zwitterionic hydrogel for controlled drug release

A controlled/ living free‐radical polymerization technique was introduced to prepared a homogeneous poly(N‐isopropylacrylamide)‐g‐poly(sulfobetaine methacrylate) hydrogel (RG) possessing a highly porous architecture via two steps. Compared to a poly(N‐isopropylacrylamide)‐co‐poly(sulfobetaine methacrylate) hydrogel (CG) prepared by conventional radical polymerization, RG exhibited a much faster shrinking rate (it lost over 72% of the water in 15 min) in response to the temperature changes. The release behaviors of tetracycline hydrochloride (TCHC) of the hydrogels indicated the TCHC release from the RG could be prolonged to 48 h at 37°C; this was much longer than that for CG (5 h at 37°C). Bovine serum albumin (BSA) was chosen as the model protein to examine the low‐fouling properties of the RG. The BSA adsorption data showed that improved antifouling properties could be achieved by the RG at both 25 and 37°C. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39816.     

Hollow,pH‐sensitive calcium–alginate/poly(acrylic acid) hydrogel beads as drug carriers for vancomycin release

In this study, hollow calcium–alginate/poly(acrylic acid) (PAA) hydrogel beads were prepared by UV polymerization for use as drug carriers. The hollow structure of the beads was fortified by the incorporation of PAA. The beads exhibited different swelling ratios when immersed in media at different pH values; this demonstrated that the prepared hydrogel beads were pH sensitive. A small amount (<9%) of vancomycin that had been incorporated into the beads was released in simulated gastric fluid, whereas a large amount (≤67%) was released in a sustained manner in simulated intestinal fluid. The observed drug‐release profiles demonstrated that the prepared hydrogel beads are ideal candidate carriers for vancomycin delivery into the gastrointestinal tract. Furthermore, the biological response of cells to these hydrogel beads indicated that they exhibited good biological safety and may have additional applications in tissue engineering. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Synthesis,characterization, and swelling behavior of new pH‐sensitive hydrogels derived from copolymers of 2‐hydroxyethyl methacrylate and 2‐(diisopropylamino)ethylmethacrylate

The aim of this work was to synthesize and to characterize new pH‐sensitive hydrogels that can be used in the controlled release of drugs, useful for dermal treatments or ophthalmology's therapies. Copolymers containing 2‐hydroxyethyl methacrylate (HEMA) with different amounts of 2‐(diisopropylamino)ethyl methacrylate (DPA) (10 and 30 wt %) and different amounts of crosslinker agent, ethylene glycol dimethacrylate (EGDMA) (1 and 3 wt %) were prepared by bulk photo‐polymerization. The copolymers were fully characterized by using Fourier‐transform infrared (FTIR) spectra, differential scanning calorimetry, thermogravimetric analysis, UV–visible spectroscopy, and measuring water content and dynamic swelling degree. The results show that modifications in the amount of DPA and/or crosslinker in the hydrogel produce variations in the thermal properties. When adding of DPA, we observed an increase in the thermal stability and decomposition temperature, as well as a change in the mechanism of decomposition. Also a decrease in the glass transition temperature was observed with regard to the value for pure pHEMA, by the addition of DPA. The water content of the hydrogels depends on the DPA content and it is inversely proportional to both the pH value and the crosslinking degree. Pure poly‐HEMA films did not show important changes over the pH range studied in this work. The dynamic swelling curves show the overshooting effect associated with the incorporation of DPA, the pH of the solution, and the crosslinking density. On the other hand, no important variations in the optical properties were observed. The synthesized hydrogels are useful as a drug delivery pH‐sensitive matrix. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Dual‐stimuli‐responsive polymer‐coated mesoporous silica nanoparticles used for controlled drug delivery

In this article, a temperature‐ and pH‐responsive delivery system based on block‐copolymer‐capped mesoporous silica nanoparticles (MSNs) is presented. A poly[2‐(diethylamino)ethyl methacrylate)] (PDEAEMA)‐b‐poly(N‐isopropyl acrylamide) (PNIPAM) shell on MSNs was obtained through the surface‐initiated atom transfer radical polymerization. The block copolymer PDEAEMA‐b‐PNIPAM showed both temperature‐ and pH‐responsive properties. The release of the loaded model molecules from PDEAEMA‐b‐PNIPAM‐coated MSNs could be controlled by changes in the temperature or pH value of the medium. The as‐desired drug‐delivery carrier may be applied to biological systems in the future. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42395.     

Preparation and characterization of thermo‐sensitive poly(vinyl alcohol)‐based hydrogel as drug carrier

Poly(vinyl alcohol)s (PVA) with high and low molecular weights were chemically modified by introducing acetaldehyde onto the polymer backbone to induce thermal‐responsive properties. The influence of both molecular weight ( ) and acetalization degree on the lower critical solution temperature (LCST) of thermo‐sensitive polymer was investigated. Moreover, a temperature responsive hydrogel was prepared by controlled cross‐linking of acetalized poly(vinyl alcohol) (APVA) and glutaraldehyde. As a model drug, ciprofloxacin was introduced into the prepared thermal sensitive hydrogel to reveal the drug loading and release behaviors. The structure, thermo‐sensitivity, swelling/deswelling kinetics, morphology, and drug loading/release behaviors were also investigated. The results indicated that the APVA polymer solution exhibited temperature responsivity, and APVA with high acetalization degree showed low LCST, whereas those with high PVAs showed high LCST. Meanwhile, morphology study was identical with the swelling/de‐swelling behavior. The loading and release of ciprofloxacin were controllable. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39720.     

Dual responsive polymeric bionanocomposite gel beads for controlled drug release systems

Scientists are searching potential solutions for cancer treatments as well as ways to avoid the side effects of anti‐cancer agents, via targeted drug delivery. The aim of this research is to propose dual responsive beads based on sodium alginate (SA), methylcellulose (MC), and magnetic iron oxide nanoparticles (MIONs) for controlled release of 5‐Fluorouracil (5‐FU) as model drug. The beads were prepared by the dual crosslinking of SA and MC in the presence of MIONs. The structural, thermal, morphological, magnetic characteristics as well as the release profile of 5‐FU were studied. The characterization results showed that the drug molecules and MIONs were well dispersed in the polymeric matrix. The cumulative release percentage was ca. 80% at pH = 4.2 and 40% at pH = 7.2 after 6 h. Thus, the sensitivity of beads on the pH value was verified. Moreover, the release profile exhibited reduction with an increase in the concentration of MIONs under an external magnetic field. The obtained results confirmed the dual sensitive release of 5‐FU (i.e., PH/magnetic) that can be used for the targeted and controlled drug delivery systems. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45143.     

Quinone propionic acid‐based redox‐triggered polymer nanoparticles for drug delivery: Computational analysis and in vitro evaluation

Redox‐responsive polymers with pendant quinone propionic acid groups as a redox trigger were optimized by computational modeling to prepare efficient redox‐triggered polymer nanoparticles (NPs) for drug delivery. Lipophilicities at complete reduction of redox‐responsive polymers (<5000 Da) constructed with adipic acid and glutaric acid were remarkably reduced to range from ?6.29 to ?0.39 compared with nonreduced state (18.87–32.46), suggesting substantial polymer solubility reversal in water. Based on this hypothesis, redox‐responsive NPs were prepared from the synthesized polymers with paclitaxel as model cancer drug. The average size of paclitaxel‐loaded NPs was 249.8 nm and their reconstitutions were stable over eight weeks. In vitro drug release profiles demonstrated the NPs to release >80% of paclitaxel over 24 h at a simulated redox‐state compared with 26.5 to 41.2% release from the control. Cell viability studies revealed that the polymer was nontoxic and the NPs could release paclitaxel to suppress breast cancer cell growth. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40461.     

Swelling kinetics,mechanical properties,and release characteristics of chitosan‐based semi‐IPN hydrogels

Two series of pH‐sensitive semi‐interpenetrating network hydrogels (semi‐IPN) based on chitosan (CS) natural polymer and acrylamide (AAm) and/or N‐hydroxymethyl acrylamide (HMA) monomers by varying the monomer and CS ratios were synthesized by free radical chain polymerization. 5‐Fluorouracil (5‐FU), a model anticancer drug, has been added to the feed composition before the polymerization. The characterization of gels indicated that the drug is molecularly dispersed in the polymer matrix. The swelling kinetics of drug‐loaded gels have decreased with increased HMA content at 37°C in both distilled water and buffer solutions with a pH of 2.1 or 7.4. Elastic modulus of the gels increased with the increase in HMA content and higher CS concentration enhanced the elastic modulus positively. Moreover, cumulative release percentages of the gels for 5‐FU were ca. 10% higher in pH 2.1 than those in pH 7.4 media. It was determined that they can be suitable for the use in both gastric and colon environments. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41886.     

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

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

Thermally and magnetically dual‐responsive mesoporous silica nanospheres: preparation,characterization, and properties for the controlled release of sophoridine

Novel thermally and magnetically dual‐responsive mesoporous silica nanoparticles [magnetic mesoporous silica nanospheres (M‐MSNs)–poly(N‐isopropyl acrylamide) (PNIPAAm)] were developed with magnetic iron oxide (Fe₃O₄) nanoparticles as the core, mesoporous silica nanoparticles as the sandwiched layer, and thermally responsive polymers (PNIPAAm) as the outer shell. M‐MSN–PNIPAAm was initially used to control the release of sophoridine. The characteristics of M‐MSN–PNIPAAm were investigated by transmission electron microscopy, Fourier transform infrared spectroscopy, X‐ray diffraction, thermogravimetry, N₂ adsorption–desorption isotherms, and vibrating specimen magnetometry analyses. The results indicate that the Fe₃O₄ nanoparticles were incorporated into the M‐MSNs, and PNIPAAm was grafted onto the surface of the M‐MSNs via precipitation polymerization. The obtained M‐MSN–PNIPAAm possessed superparamagnetic characteristics with a high surface area (292.44 m²/g), large pore volume (0.246 mL/g), and large mesoporous pore size (2.18 nm). Sophoridine was used as a drug model to investigate the loading and release properties at different temperatures. The results demonstrate that the PNIPAAm layers on the surface of M‐MSN–PNIPAAm effectively regulated the uptake and release of sophoridine. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40477.     

Synthesis and characterization of 2‐hydroxyethylmethacrylate/2‐(3‐indol‐yl)ethylmethacrylamide‐based novel hydrogels as drug carrier with in vitro antibacterial properties

In this study, a new cationic monomer 2‐(3‐indol‐yl)ethylmethacrylamide (IEMA) derived from tryptamine was synthesized in a single step and characterized by Fourier transform infrared (FTIR), ¹H‐NMR, and ¹³C‐NMR. Then, one‐step preparation of novel poly[2‐hydroxyethylmethacrylate‐c‐2‐(3‐indol‐yl)ethylmethacrylamide], or p(HEMA‐c‐IEMA), copolymeric hydrogels has been performed successfully with IEMA and 2‐hydroxyethylmethacrylate (HEMA) as monomers using free radical aqueous polymerization. The hydrogels were characterized with scanning electron microscopy, FTIR, elemental analysis, thermogravimetric analysis, and texture profile analysis instruments. p(HEMA‐c‐IEMA) hydrogels were used for swelling, diffusion, drug release, and antibacterial activity studies. The drug‐release behavior of the hydrogels was determined as a function of time at 37 °C in pH 1.2 and 7.2. The swelling and drug‐release studies showed that an increased IEMA amount caused a higher increase in swelling and drug‐release values. Additionally, zero‐order, first‐order, and Higuchi equation kinetic models were applied to the drug‐release data, and the data fit well in the Higuchi model, and the Peppas power‐law model was applied to the release mechanism. Finally, the antibacterial activities of the hydrogels were screened against Gram‐positive bacteria (Bacillus cereus and Staphylococcus aureus) and Gram‐negative bacteria (Escherichia coli and Salmonella typhimurium). © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45550.     

Thermoresponsive self‐assembled nanovesicles based on amphiphilic triblock copolymers and their potential applications as smart drug release carriers

A series of thermoresponsive triblock copolymers, methoxy poly(ethylene oxide)‐b‐poly(ε‐caprolactone)‐b‐poly(N‐isopropylacrylamide) (mPEO‐b‐PCL‐b‐PNIPAM), with different PCL and PNIPAM block lengths, were synthesized by a combination of ring opening polymerization and reversible addition‐fragmentation chain transfer polymerization techniques. The triblock copolymers undergo self‐assembly in aqueous solutions forming stable nanovesicles of various sizes with a lipid membrane structure similar to body cells as revealed by transmission electron microscopy. The nanovesicle is thermoresponsive, that is, its size is tunable using the temperature as a switch: shrinks at a temperature above the lower critical solution temperature (LCST) and expands at a temperature below the LCST. The corresponding LCST of the triblock copolymers is adjustable by varying the PNIAM segment length as well as the PCL segment length and covers a range from 33.9 to 41.0°C in water. The diameter of nanovesicles for mPEO_3k‐b‐PCL_5k‐b‐PNIPAM_13.2k is about 177.7 nm below the LCST and 138.9 nm above the LCST, as determined by dynamic light scattering. It was demonstrated using indomethacin, a popular anti‐inflammation medicine, that the triblock copolymers can effectively act as a drug release carrier under the right human physiological conditions, that is, store the drug at a lower temperature and release it at a higher temperature, possibly targeting at the lesion sites of human body. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41361.     

Preparation and aqueous solution behavior of a ph‐responsive branched copolymer based on 2‐(diethylamino)ethyl methacrylate

pH‐Responsive amphiphilic branched copolymers were prepared from poly(ethylene glycol) methyl ether methacrylate (PEGMA), 2‐(diethylamino)ethyl methacrylate (DEAEMA), 2‐(tert‐butylamino)ethyl methacrylate (tBAEMA), and ethylene glycol dimethacrylate (EGDMA) utilizing a thiol‐modified free radical polymerization. The molecular structures of copolymers were confirmed by proton nuclear magnetic resonance spectroscopy (¹H NMR) and triple‐detection gel permeation chromatography (tri‐GPC). The aqueous solution behaviors of the obtained copolymers were investigated by dynamic light scattering (DLS). The DLS data showed that about 16 nm polymer particles comprising of hydrophobic poly(tert‐butylamino)ethyl methacrylate (PtBAEMA) and poly(diethylaminoethyl methacrylate (PDEAEMA) core, hydrophilic PEGMA corona were formed above pH 8. With the decrease of pH from 8 to 6, a dramatic increase in the hydrodynamic radius of polymer particles from 16 nm to 130 nm was observed resulting from the protonation of the PDEAEMA segment. Moreover, in vitro drug release behaviors of the resulting polymer assemblies at different pH values were also investigated to evaluate their potential as sustained release drug carriers. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42183.     

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     

Polymeric PEGylated nanoparticles as drug carriers: How preparation and loading procedures influence functional properties

The application of emerging nanotechnologies in medicine showed in the last years a significant potential in the improvement of therapies. In particular, polymeric nanocarriers are currently tested to evaluate their capability to reduce side effects, to increase the residence time in the body and also to obtain a controlled release over time. In the present work a novel polymeric nanocarrier was developed and optimized to obtain, with the same chemical formulation, three different typologies of nanocarriers: dense nanospheres loaded with an active molecule (1) during nanoparticle formation and (2) after the preparation and (3) hollow nanocapsules to increase the starting drug payload. Synthetic materials considered were PEGylated acrylic copolymers, folic acid was used as model of a hydrophobic drug. The main aim is to develop an optimized nanocarrier for the transport and the enhanced release of poorly water‐soluble drugs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41310.