Poly(2-hydroxyethyl acrylate) hydrogels containing hyper-branched poly(amidoamine) for sustained drug release

Hydrogels containing hyper-branched poly(amidoamine) (hb-PAMAM) microenvironments were suggested for the sustained release of ionizable drugs. For this purpose, a series of poly(2-hydroxyethyl acrylate) (PHEA) hydrogels containing hb-PAMAM (PHEA-hb-PAMAM) were prepared by copolymerization of 2-hydroxyethyl acrylate with acryl-terminated hb-PAMAM. The hb-PAMAM was synthesized by the Michael addition reaction of triacryloylhexahydro-1,3,5-triazine (TT) and piperzaine (PZ). By using nonionic Tegafur and ionizable salicylic acid (SA) as model drugs, the release mechanisms of drugs from PHEA-hb-PAMAM hydrogels were investigated. Compared with the release kinetic of Tegafur, the release rate of SA from the hydrogels was evidently slowed down. Moreover, the release rate of SA can be modulated by the addition of salt. This can be attributed to the ionic interaction of SA with hb-PAMAM microenvironments. By analyzing the release kinetics of SA from the hydrogels, it was found that the release of SA followed non-Fickian diffusion.     

Hydrogel-shelled biodegradable microspheres for sustained release of encapsulants

Biodegradable microparticles are promising for the sustained release of encapsulated lipophilic drugs. In particular, the microparticles with uniform size show excellent linearity of cumulated release over time with minimized initial burst. Here, we encapsulate the biodegradable microparticles with a hydrogel shell to improve the controllability over the sustained release and suspension stability. With a capillary microfluidic device, monodisperse oil-in-water-in-oil (O/W/O) double-emulsion droplets are produced to have a toluene solution of polylactic acid (PLA) in the core and sodium alginate and calcium-ethylenediaminetetraacetic acid (EDTA) complex in the shell, whereas the continuous oil phase contains acetic acid. As the toluene evaporates, PLA consolidates to form a microsphere in the core. At the same time, acetic acid diffuses from the continuous phase to the water layer, which causes the dissociation of the Ca-EDTA complex and the gelation of alginate. The hydrogel-shelled PLA microspheres are transferred from the oil to an aqueous solution of calcium chloride, which further tightens the gel shell. The resulting core-shell microspheres show sustained release of encapsulants for extended periods as the hydrogel shell serves as a diffusion barrier. Moreover, the hydrogel shells prevent interparticle agglomeration and adhesion to the solid walls, securing high suspension stability during the injection.     

Ionic liquid–modified cellulosic hydrogels for loading and sustained release of selenourea: an ensuing inhibition of tyrosinase activity

Cellulose-based hydrogel materials were prepared and modified with tannic acid and l-methionine using ionic liquid as the solvent. The gels were prepared to develop a sustained release medium for selenourea (SeU). The drug delivery characteristics of selenourea-loaded cellulose (CSeU), selenourea-loaded tannic acid-modified cellulose (CTSeU), and selenourea-loaded L-methionine-modified cellulose (CMSeU) were investigated in aqueous media and simulated gastric fluid (SGF) media. This modified gel beads have been characterized using field emission scanning electron microscope, X-ray energy-dispersive spectroscopy, Fourier transform infrared spectroscopy, thermogravimetry–differential thermal analysis and swelling properties and compared with those of the unmodified ones. We also investigated the inhibitory effects of SeU released from these gels on the activity of mushroom tyrosinase. Out of all the gel materials, CTSeU showed maximum SeU release both in water and SGF media. However, tyrosinase inhibitory action in PBS medium was comparable for all the three gel materials.     

Radiation synthesis of polyaspartamide functionalised hydrogels for sustained release of fragrances

The aim of the present investigation is to assess the possibility of obtaining a biocompatible material device which is able to deliver oil-soluble fragrances in air over a length of time. Aqueous solutions of polyaspartamide functionalised with glycidyl methacrylate have been crosslinked through gamma irradiation in the presence of a lipophilic model fragrance, emulsified prior to irradiation. Two emulsification conditions have been considered at two different concentrations of both fragrance and surfactant in water. Chemical hydrogels have been obtained in correspondence to two irradiation absorbed doses and have been characterised for their solubility properties and swelling ability in water. Both static and dynamic release experiments of the fragrance in air have been performed and the release behaviour related to the hydrogel network structure and its water retention properties.     

Injectable poly(ethylene glycol) hydrogels for sustained doxorubicin release

Water‐soluble poly(ethylene glycol) derivatives with multiple “clickable” mercapto groups or double bonds were facilely synthesized in a large scale by direct polycondensation of oligo(ethylene glycol) diol with mercaptosuccinic acid or maleic acid catalyzed by scandium trifluoromethanesulfonate under mild conditions. Injectable hydrogels containing doxorubicin hydrochloride (DOX · HCl) could be rapidly formed using these poly(ethylene glycol) derivatives as precursors via in situ thiol‐ene “click” reaction under physiological conditions without light, initiator, or metal catalyst. DOX · HCl could be sustained released from the hydrogels as a result of the hindrance of the three dimensional hydrogel network on the drug molecules, which makes this kind of DOX‐loaded hydrogels a promising candidate for localized tumor chemotherapy. Copyright © 2016 John Wiley & Sons, Ltd.     

Adsorption and controlled release of Chlortetracycline HCl by using multifunctional polymeric hydrogels

Adsorption and controlled release of Chlortetracycline HCl to and from multifunctional polymeric materials (HEMA/MAA) hydrogels were investigated. P(HEMA/MAA) hydrogels were synthesized by gamma radiation-induced copolymerization of 2-hydroxyethylmethacrylate (HEMA) and methacrylic acid (MAA) in aqueous solution. The influence of copolymer composition and pH value of the surrounding medium on the type of water diffusion into the glassy polymer were discussed. Drug, Chlortetracycline HCl containing hydrogels, with different drug concentration to polymer ratios, was loaded by direct adsorption method. The influence of MAA content in the gel on the adsorption capacities of hydrogel was studied. Chlortetracycline HCl adsorption capacity of hydrogels was found to increase from 8 to 138 mg Chlortetracycline HCl per gram dry gel with increasing amount of MAA in the gel system and drug concentration. The effect of pH on the releasing behavior of Chlortetracycline HCl from gel matrix was investigated. In vitro drug release studies in different buffer solutions show that the basic parameters affecting the drug release behavior of hydrogel are the pH of the solution and MAA content of hydrogel.     

Molecularly imprinted hydrogels for sustained release of sunitinib in breast cancer therapy

The present work reports on the synthesis of a molecularly imprinted polymer (MIP) based on methacrylic acid and ethylene glycol dimethacrylate for sunitinib delivery. Sunitinib (SUT) is a tyrosine kinase inhibitor used in many cancer diseases. Like the majority of the anticancer drugs, SUT suffers of a low bioavailability, and at the same time, it is characterized by a narrow therapeutic window. In order to reduce drug systemic toxicity, we synthesized a MIP‐based drug delivery system for SUT‐controlled release. MIP was obtained by bulk polymerization through the so‐called noncovalent approach. Rebinding experiments were performed to evaluate the success of the imprinting process and the ability of MIP to bind in a specific and selective fashion the template molecule. Resulting data showed that sunitinib rebinding percentage was 70%, while nonimprinted polymer (NIP) rebinding percentage was 46%. A not significant difference was observed between MIP and NIP in semaxanib binding experiments. Moreover, the drug release profiles were studied for both MIP and NIP. A sustained release was observed from sunitinib‐loaded MIP during 24 hours, reaching 58% after 6 hours and 76% at the end‐point. NIP, on the contrary, released almost 90% of the loaded drug within 6 hours. Furthermore, the drug carrier was tested in vitro against MCF‐7 cells, in which the cytotoxic effect of sunitinib released from MIP reached the maximum after 72 hours, while NIP completed its effect within 48 hours. These results demonstrated that molecularly imprinted polymers are suitable systems for SUT release.     

Novel interpenetrating smart polymer networks grafted onto polypropylene by gamma radiation for loading and delivery of vancomycin

Gamma radiation was used in every step of the synthesis of a sequential interpenetrating polymer network made of two “smart” polymers: poly(acrylic acid) (PAAc) and poly (N-isopropylacrylamide) (PNIPAAm), the latter grafted onto polypropylene (PP) films (PP-g-PNIPAAm) with the aim of developing medicated coatings for medical devices. Three steps were followed for obtaining net-PP-g-PNIPAAm-inter-net-PAAc: graft copolymerization of PNIPAAm onto PP films by gamma pre-irradiation oxidative method, cross-linking of PP-g-PNIPAAm by gamma irradiation in water to form the first network, with or without N,N′-methylenebis(acrylamide) (MBAAm), and finally the formation of the second network through the polymerization and cross-linking of AAc inside cross-linked PP-g-PNIPAAm by a low gamma radiation dose of 2.5 kGy. The films were characterized regarding the amount of grafted polymers and their composition (FTIR-ATR), thermal behavior (DSC), temperature- and pH-responsive swelling and contact angle (critical pH 6 and lower critical solution temperature ∼33 °C), and loading and release rate of vancomycin. Drug loading was driven by specific interactions between vancomycin and PAAc. Drug-loaded films sustained the delivery for several hours at pH 7.4 and provided release rate values adequate for killing bacteria attempting to adhere the surface of the films.     

Cyclodextrin/polyethylenimine-based supramolecular nanoparticles for loading and sustained release of ATP

A new supramolecular nanoparticle PEI/SCD was successfully constructed, showing the loading/sustained release abilities towards ATP.     

Poly(maleic anhydride-co-acrylic acid)/poly(ethylene glycol) hydrogels with pH- and ionic-strength-responses

<正>Poly(maleic anhydride-coacrylic acid),P(MA-AA),was synthesized by the free-radical copolymerization of maleic anhydride with acrylic acid,and fast responsive pH-sensitive poly(maleic anhydride-co-acrylic acid)/polyethylene glycol,P(MA-AA)/PEG,hydrogels were prepared using PEG as macromolecular cross-linking agent.FT-IR and ~1H-NMR spectrometry were applied to characterize the structure of P(MA-AA).The influences of pH and ionic strength on the swelling behavior of P(MA-AA)/PEG hydrogels and the swelling-deswelling changes along with the repeated changes between acid and alkali conditions were studied.The results showed that there was a hundredfold difference in the swelling ratios between the conditions of acid and alkali,and the swelling capability could not be weakened after multiple swelling-deswelling cycles.The results of swelling kinetics demonstrated that the response rate of P(MA-AA)/PEG hydrogels was very fast,because the swelling transition points always occurred at 10 min.The pH-responsive hydrogels reported here might be a smart material for potentially applications in many areas,including biosensors,drug-delivery devices and tissue engineering.     

Synthesis and characterisation of chemically crosslinked N-vinyl pyrrolidinone (NVP) based hydrogels

Crosslinked complexes of polyvinyl pyrrolidinone-polyacrylic acid (PVP-PAA) were prepared from a mixture of NVP, AA and ethyleneglycol dimethacrylates. The FTIR spectra of PVP-PAA copolymer complexes indicates both hydrogen bonded and non-hydrogen bonded PVP. Swelling of the PVP-PAA complex in a higher pH medium is significantly different from results in low pH solutions. Above the critical pH of the copolymer the carboxylic acid group of AA ionize. Therefore there is a reduction in the intermolecular bonding and so the hydrogels tend to swell to a greater degree yielding higher ‘water content’ and ‘water uptake’ values. The rheometry results indicated that there was a significant difference in the comparative gel strength at different pHs due to the increased water uptake. It was also found that by varying the molecular weight of the crosslinking agent an increase in comparative gel strength could be achieved.     

Synthesis of three-dimensional hydrogels based on poly(glycidyl methacrylate-alt-maleic anhydride): Characterization and study of furosemide drug release

In the present work, three-dimensional drug carriers were synthesized via chemical modification of poly (glycidyl methacrylate-alt-maleic anhydride) P(GMA-alt-MA) by isopropylamine (IPA) and ethylenediamine (EDA) with different molar ratios. Then furosemide drug (FR) was loaded on the hydrogels and studied for its slow release in phosphate-buffered saline (PBS) solution (pH = 7.41) at 37 °C. According to the obtained results, the sample with the lowest amount of crosslinking agent (Sample A) showed the highest swelling ratio in comparison to the others. By increasing the rigidity of carrier in the result of increasing the crosslinker density, the amount of the released drug was decreased. However, the release rate for all of samples (slope of the profiles) were rather similar. All the synthesized carriers have shown pH dependent properties and the maximum release rate was shown in basic pH. Also, the drug release experiments in different temperatures showed almost thermal sensitivity properties for synthesized carriers and release rate become faster by increasing the medium temperature. The FT-IR, TGA, and FE-SEM analyses were carried out for characterization of prepared samples and the swelling behavior of prepared hydrogels were measured too. Investigation of the release data with different mathematical models showed the highest adaption with the Higuchi model for all samples.     

Synthesis and characterization of poly(methacrylic acid) hydrogels for metoclopramide delivery

Polymeric hydrogels based on biocompatible materials, methacrylic acid (MAA), were designed and synthesized. Synthesis was carried out by free-radical copolymerization using potassium persulfate as initiator and N,N^′-methylenebisacrylamide as crosslinker. Hydrogels were also characterized by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance spectroscopy (¹H NMR) and differential scanning calorimetry (DSC). DSC was used for the quantitive determination of the amounts of freezing and non-freezing water of the hydrogels with 0.5% of N,N^′-methylenebisacrylamide. Equilibrium swelling of hydrogels was studied in phosphate buffer of physiological pH (1.0, 4.0, 7.4 and 8.5) at 37 °C. The swelling kinetic of the hydrogels were studied and the kinetic characteristic constant of copolymeric systems, k, and the exponent which characterizes the mechanism of water transport at short times, n, were obtained. Metoclopramide hydrochloride was entrapped into the hydrogels by sorption and the “in vitro” release profile of this drug was established in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). It was observed that the drug release mechanism was non-Fickian.     

Preparation, characterization, swelling and in vitro drug release behaviour of poly[N-acryloylglycine-chitosan] interpolymeric pH and thermally-responsive hydrogels

Novel biodegradable pH- and thermal-responsive interpenetrating polymer network (IPN) hydrogels were prepared for controlled drug delivery studies. The IPN hydrogels were obtained in mild aqueous acid media by irradiation of solutions of N-acryloylglycine (NAGly) mixed with chitosan, in the presence of glutaraldehyde as a crosslinking agent and using 2,2-dimethoxy-2-phenyl acetophenone as photoinitiator. These hydrogels were subjected to equilibrium swelling studies at different temperatures (25 °C, 37 °C and 45 °C) in buffer solutions of pH 2.1 and 7.4 (similar to that of gastric and intestinal fluids respectively). 5-Fluorouracil (5-FU) was entrapped in the hydrogels, and drug release studies carried out at 37 °C in buffer solutions at pH 2.1 and 7.4.     

Liposomal drugs dispersed in hydrogels. Effect of liposome, drug and gel properties on drug release kinetics

Release of calcein and griseofulvin (GRF) from control (gels in which solutes are dissolved in) and liposomal gels was studied using agarose-assisted immobilization as a technique to separate gels from drug-receptor compartments. Liposomes composed of phosphatidylcholine (PC) or distearoyl-glycero-PC and cholesterol (DSPC/Chol), and incorporating calcein or GRF were prepared by thin film hydration. After cleaning the liposomes they were dispersed in different hydrogels (carbopol 974 [1, 1.5 or 2% (w/w)], hydroxylethyl-cellulose (HEC) [4% (w/w)], or a mixture of the two), and release of calcein or GRF was followed by fluorescence or photometric technique, respectively. Results show that calcein release from liposomal gels is slower compared to control gels, and can be further retarded by using rigid-membrane liposomes (faster release from PC-liposome compared to DSPC/Chol-liposome gels). Additionally, calcein release is not affected by the lipid amount loaded (in the range from 2 to 8 mg/ml), therefore solute loading can be controlled according to needs.

Oppositely, GRF release from liposomal gels is determined by drug loading. At high drug loading levels (compared to GRF aqueous solubility), GRF is released with constant rate from liposomal gels irrespective of liposome type (PC or DSPC/Chol). Thereby, for amphiphilic/lipophilic drugs, drug properties (solubility, log P) determine the system behavior.

Calcein and GRF release from control carbopol gels is faster compared to HEC and mixture gels. The same is true for calcein in liposomal gels. Carbopol gel rheological properties were found to be significantly different (compared to the other gels), implying that these characteristics are important for drug diffusion from gels.     

新型环氧树脂基液晶光定向层材料的合成与性能研究

经双酚A型环氧树脂与苯胺缩聚反应,制备含有羟基的先驱聚合物EP-AN,通过EP-AN上羟基与肉桂酰氯的酯化反应,制备了侧链带有肉桂酸酯基团的光敏聚合物EP-AN-CI.用核磁共振(1HNMR)、傅里叶红外光谱(FTIR)和热分析等手段确定了上述聚合物的结构与性能.用FTIR等方法表征了EP-AN-CI的光交联反应.经线性偏振光聚合技术(LPP)处理聚合物EP-AN-CI膜制备成液晶定向层,通过装配液晶盒和偏光显微镜观察表明,所制备的定向层具有很好的定向能力,该聚合物是一类具有潜在应用价值的新型液晶光定向层材料.     

Preparation and characterization of biodegradable gelatin-PAAm-based IPN hydrogels for controlled release of maleic acid to improve the solubility of phosphate fertilizers

In this study, interpenetrating polymer network (IPN) hydrogel systems including maleic acid (MA) were constituted to improve the solubility of phosphate fertilizers. A series of full and semi-IPN hydrogels were prepared from various gelatin/polyacrylamide mixtures by using two different cross-linkers. The effects of polymer composition on the morphological structures and swelling behaviors of the hydrogels were investigated. The swelling values of all hydrogels were found to be in between 435% and 830%. MA release from load0ed hydrogels was followed and it was determined that MA-loaded hydrogels efficiently decreased pH and improved the solubility of Ca₃(PO₄)₂ in releasing medium.     

Gelator-polysaccharide hybrid hydrogel for selective and controllable dye release

In this paper, 1,4-bi(phenylalanine-diglycol)-benzene (PDB) based Low-Molecular-Weight-Gelator (LMWG) hydrogels are modified using hydrophilic polysaccharide (sodium alginate). A set of techniques including Fourier transform infrared (FT-IR) spectroscopy, ¹H Nuclear Magnetic Resonance (¹H NMR), X-ray powder diffraction (XRD), Ultraviolet-Visible (UV-Vis), and circular dichroism (CD) had confirmed a β-turn arrangement of PDB gelators and a semi-interpenetrating network (semi-IPN), which was formed through hydrogen bonds between LMWG fibers and polysaccharide chains. The evaluation of physicochemical properties of hydrogels indicates that gelator-polysaccharide hybrid hydrogels possess better mechanical and water retention properties than LMWG hydrogels. The release study of dyes (model drug) from both LMWG and hybrid hydrogels was carried out. Compared with PDB based hydrogels, hybrid hydrogels show a selective and controllable release property for certain dyes. The results suggest LMWG-polysaccharide hybrid gels may find potential applications as promising drug delivery vehicles for drug molecules.     

Glutaraldehyde cross-linked epoxyaminated chitosan as an adsorbent for the removal and recovery of copper(II) from aqueous media

A novel glutaraldehyde cross-linked epoxyaminated chitosan (GA-C-ENCS) prepared through chemical modification was used as an adsorbent for the removal and recovery of Cu(II) from aqueous media. The adsorbent was characterized by FTIR, SEM-EDS, ESR, TG/DTG, BET-surface area and potentiometric titration. The Cu(II) adsorption process, which was pH dependent showed maximum removal at pH 6.0. Adsorption equilibrium was achieved within 3 h. The adsorption of Cu(II) followed a reversible-first-order kinetics. The equilibrium data were evaluated using the Langmuir, Freundlich and Dubinin–Radushkevich isotherm models. The best interpretation for the equilibrium data was given by the Dubinin–Radushkevich isotherm. The adsorption capacity of the adsorbent increased from 3.11 to 3.71 mmol g⁻¹ when the temperature was increased from 20 to 50 °C. The complete removal of 20.7 mg L⁻¹ Cu(II) from electroplating industry wastewater was achieved by 0.4 g L⁻¹ GA-C-ENCS. Regeneration experiments were tried for four cycles and the results indicate a capacity loss of <7.0%.