Photopolymerization of alicyclic methacrylate hydrogels for controlled release

Alicyclic hydroxy methacrylate monomer, o‐hydroxycyclohexyl methacrylate (HCMA), was synthesized and characterized by Fourier transformed infrared spectroscopy (FT‐IR) and proton nuclear magnetic resonance spectroscopy (¹H‐NMR). Photopolymerization kinetics of HCMA was investigated via real‐time infrared spectroscopy (RT‐IR). Polymeric network hydrogels based on hydroxyethyl methacrylate (HEMA) and HCMA were prepared by using the photopolymerization technique. Mechanical strength, swelling characteristic, and controlled release behavior of hydrogels with various feed compositions were studied. Poly(HEMA‐co‐HCMA) hydrogel had higher storage modulus than that of poly(HEMA) hydrogel as investigated by dynamic mechanical analysis (DMA). Acid orange 8 was used as a model drug for the investigation of drug release behavior of copolymeric hydrogels. Results indicated that increase in HCMA ratio in hydrogel composition could reduce the swelling rate and prolong the release time. Scanning electron microscopy (SEM) was also utilized to study the surface morphology of hydrogels, and the results indicated that HCMA content influenced pore diameter on the hydrogel surface. Copyright © 2008 John Wiley & Sons, Ltd.     

Swelling kinetics and release characteristic of crosslinked chitosan: Polyether polymer network (semi-IPN) hydrogels

The aqueous swelling kinetics of a series of crosslinked chitosan (cr-CS) with glutaraldehyde (GA) interpenetrating polyether hydrogels have been studied as functions of pH, the N-deacetylation degree of chitosan, the amount of crosslinking agent, the electrolyte composition in solution, temperature, and gel composition. Based on these results, the swelling mechanism of the hydrogels was discussed. The release profiles of chlorhexidini acetas from the semi-IPN were also investigated. © 1994 John Wiley & Sons, Inc.     

Synthesis of dual responsive cyclotriphosphazene‐based IPN hydrogels for controlled release of chemotherapeutic agent

Dual responsive cyclotriphosphazene (CTP)‐based hydrogels have been synthesized for a controlled release of FU, a hydrophilic drugs. These hydrogels composed of mono (methacryloyl‐2‐ethoxy)‐pentakis(N¹,N¹‐dimethylpropane‐1,3‐diamino)‐cyclotriphosphazene (HEMA (DMPDA)₅CP), acryl amide and pectin were synthesized by free radical polymerization method using methylenebisacrylamide cross linker. The CTP hydrogels were characterized to understand the structure, drug nature in the network and morphology by FTIR, DSC, XRD and SEM, respectively. In this paper, the swelling (dynamic and equilibrium) properties of cyclotriphosphazene hydrogels were investigated, showing dual (pH and thermo) responsiveness and large variation in the swelling capacity. Based on these results the structural parameters of the hydrogel networks such as the average molecular weight between cross‐links (M_c) and polymer–solvent interaction parameter (χ) were determined. The CTP hydrogels has high FU loading efficiency 65 ± 0.5. In‐vitro FU release of these hydrogels was controlled for about 24 hr also hydrogel showed a distinct initial burst. The CTP hydrogels are bearing both hydrophilic groups of pectin and hydrophobic groups of CTP exhibited dual responsive behaviors with pH and temperature. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis and characterization of novel carboxymethyl chitosan grafted polylactide hydrogels for controlled drug delivery

Novel carboxymethyl chitosan‐polylactide (CMCS‐g‐PLA) hydrogels were prepared by using 1‐(3‐dimethylaminopropyl)‐3‐ethylcarbodiimide hydrochloride/N‐hydroxysuccinimide (EDC/NHS) as crosslinking agent and catalyst at room temperature. Solid‐state ¹³C‐NMR, SEM, and FT‐IR measurements showed that PLA blocks are successfully grafted onto the CMCS main chains. DSC measurements confirmed the effective crosslinking of carboxymethyl chitosan. With increasing the amount of EDC/NHS, the crosslink destiny of CMCS‐g‐PLA copolymers is improved. The swelling ratio of CMCS‐g‐PLA hydrogels is pH dependent, showing a minimum in the pH range of 3 to 5. Rheological studies confirmed the formation of hydrogels. The higher the crosslinking density, the higher the storage modulus of hydrogels. CMCS‐g‐PLA hydrogels only slightly degrade in PBS for 10 days. In the presence of lysozyme, however, hydrogels with low crosslink density are totally degraded in 10 days. Drug release studies show that after 96 h, 95% of thymopentin is released under in vitro conditions. Copyright © 2015 John Wiley & Sons, Ltd.     

大茴香醛改性海藻酸钠凝胶的制备及释药性能

在酸催化下使海藻酸钠与对甲氧基苯甲醛(又名大茴香醛)发生缩醛化反应,使其疏水改性,并将其制备成凝胶。利用红外(FTIR)、荧光、透射电镜(TEM)、扫描电镜(SEM)、紫外、热重分析(TGA)对产物进行了表征。结果表明,大茴香醛成功地与海藻酸钠发生了反应。该凝胶可以作为药物载体对牛血清白蛋白进行包埋释放,结果发现,改性后的产物其载药率和缓释性能比未改性的海藻酸钠有了一定的提高。     

Hybrid cross‐linked hydrogels as a technology platform for in vitro release of cephradine

Hydrogel‐based drug delivery systems can leverage therapeutically favorable upshots of drug release and found clinical uses. Hydrogels offer temporal and spatial control over the release of different therapeutic agents. Because of their tailor made controllable degradability, physical properties, and ability to prevent the labile drugs from degradation, hydrogels provide platform on which diverse physicochemical interactions with entrapped drugs cause to control drug release. Herein, we report the fabrication of novel vinyltrimethoxy silane (VTMS) cross‐linked chitosan/polyvinyl pyrrolidone hydrogels. Swelling in distilled water in conjunction with different buffer and electrolyte solutions was performed to assess the swellability of hydrogels. Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X‐ray diffraction (XRD) analysis were further conducted to investigate the possible interactions between components, thermal stability, and crystallinity of as‐prepared hybrid hydrogels, respectively. In vitro time‐dependent biodegradability, antimicrobial study, and cytotoxicity were also carried out to evaluate their extensive biocompatibility and cytotoxic behavior. More interestingly, in vitro drug release study allowed for the controlled release of cephradine. Therefore, this facile strategy developed the novel biocompatible and biodegradable hybrid hydrogels, which could significantly expand the scope of these hydrogels in other biomedical applications like scaffolds, skin regeneration, tissue engineering, etc.     

Poly (acryloyl- -proline methyl ester) hydrogels obtained by radiation polymerization for the controlled release of drugs

Thermosensitive hydrogels were obtained by radiation-induced polymerization of acryloyl- -proline methyl ester in the presence of a crosslinking agent. The measurements of equilibrium water content in the temperature range between 0° and 60°C showed that the samples swelled at low temperatures while they shrank at high temperatures. These hydrogels were used as drug delivery systems for the controlled release of insulin. In vivo studies carried out on diabetic rats ascertained a significant reduction in the hyperglycemic level in the blood which continued for about 2 months.     

Determination of glucosamine and its derivatives released from photocrosslinked gelatin hydrogels using HPLC

A simple, accurate and validated reverse‐phase high‐performance liquid chromatography (HPLC)/UV method is developed for the determination of glucosamine hydrochloride (GlcN), N‐acetyl‐glucosamine (NAG) and N‐acryloyl‐glucosamine (AGA) released from photocrosslinked gelatin hydrogels. The HPLC separation was achieved on a Shimadzu InertSustain amino column (250 × 4.6 mm, 5 µm particle size) at room temperature using a mobile phase of acetonitrile–phosphate buffer (75:25, v/v, pH 6.0) at a flow rate of 1.0 mL/min and UV detection of 194 nm. The method was validated for specificity, linearity, limit of detection and quantification, accuracy, precision, extraction recovery and solution stability. The calibration curves were with excellent linearity, with correlation coefficients (R²) >0.999 for all three drugs. The intra‐ and inter‐day variation was <3.10% and the relative error was between ?1.43 and 1.78%. The extraction recovery results ranged from 94.62 to 99.33%, demonstrating the absence of matrix effect. The sample and standard solutions were stable for more than 2 months. The method was successfully used for the analysis of released properties of drugs physically encapsulated and chemically crosslinked in the gelatin hydrogels. Copyright © 2015 John Wiley & Sons, Ltd.     

Study on slow release anti-cancer drugs prepared by radiation induced polymerization

This paper reports the research results which the anticancer drugs Ara-C with controlled slow release were made by radiation induced polymerization of monomers such as methacrylates at room temperature. Our studies showed that not only hydrophilic synthetic polymers but also hydrophobic polymers such as hydrophobic methacrylates (including MMA, EMA, and BMA) could be used to the immobilization. In vitro the rate of drugs release was controlled by the many factors such as the content of drugs, the monomer material, the crosslinking agent, the irradiation dose and the water content, etc.     

Drug release of pH/temperature-responsive calcium alginate/poly(N-isopropylacrylamide) semi-IPN beads

A series of semi-interpenetrating, polymer network (semi-IPN), hydrogel beads, composed of calcium alginate (Ca-alginate) and poly(N-isopropylacrylamide) (PNIPAAM), were prepared for a pH/temperature-sensitive drug delivery study. The equilibrium swelling showed the independent pH- and thermo- responsive nature of the developed materials. At pH=2.1, the release amount of indomethacin incorporated into these beads was about 10% within 400 min, while this value approached to 95% at pH=7.4. The release rate of the drug was higher at 37 degrees C than that at 25 degrees C and increased slightly with increasing PNIPAAM content. These results suggest that the Ca-alginate/PNIPAAM beads have the potential to be used as an effective pH/temperature sustainable delivery system of bioactive agents. [GRAPHS: SEE TEXT] A summary of the temperature- and pH-dependence on the release of the drug over a period of 450 min. The effect of the temperature on the swelling of the beads is shown in the inset.     

Sponge-like nanostructured conducting polymers for electrically controlled drug release

An electrically controlled drug release (ECDR) system based on sponge-like nanostructured conducting polymer (CP) polypyrrole (PPy) film was developed. The nanostructured PPy film was composed of template-synthesized nanoporous PPy covered with a thin protective PPy layer. The proposed controlled release system can load drug molecules in the polymer backbones and inside the nanoholes respectively. Electrical stimulation can release drugs from both the polymer backbones and the nanoholes, which significantly improves the drug load and release efficiency. Furthermore, with one drug incorporated in the polymer backbone during electrochemical polymerization, the nanoholes inside the polymer can act as containers to store a different drug, and simultaneous electrically triggered release of different drugs can be realized with this system.     

Synthesis of hydrophilic microspheres with LCST close to body temperature for controlled dual‐sensitive drug release

Novel stimuli‐responsive hydrophilic microspheres were prepared by free radical polymerization of hydroxyethyl methacrylate (HEMA) and methacrylic acid (MA), as hydrophilic monomers, and N‐isopropylacrylamide (NIPAAm) and N,N′‐ethylenebisacrylamide (EBA), as thermo‐sensitive monomer and crosslinker, respectively. Hydrophilic comonomers were introduced in the macromolecular network to synthesize materials with tunable thermal behavior. In addition, by introducing in the polymerization feed both a hydrophilic and a pH‐sensitive monomer, such as MA, dual stimuli‐responsive (pH and temperature) hydrogels were synthesized. The incorporation of monomers in the network was confirmed by infrared spectroscopy, while the network density and the shape of hydrogels was found to strictly depend on the concentration of monomers in the polymerization feed. Thermal analyses showed negative thermo‐responsive behavior with pronounced water affinity of microspheres at a temperature lower than lower critical solution temperature (LCST). In our experiment, the LCST values of the hydrogels were in the range 34.6–37.5°C, close to the body temperature, and the amount of hydrophilic moieties in the polymeric network allows to collect shrinking/swelling transition temperatures higher than the LCST of NIPAAm homopolymers. In order to test the preformed materials as drug carriers, diclofenac diethylammonium salt (DDA) was chosen and drug entrapment percent was determined. Drug release profiles, in media at different temperature and pH, depend on hydrogels crosslinking degree and drug–bead interactions. By using semi‐empirical equations, the release mechanism was extensively studied and the diffusional contribute was evaluated. Copyright © 2010 John Wiley & Sons, Ltd.     

Chondroitin/polypyrrole nanocomposite hydrogels for the accurate release of 5-fluorouracil by electrical stimulation

The development of electro-stimulated drug release devices is an innovative approach to attain the drug delivery in accurate doses at target sites in a programmed manner. In this work, novel electroactive nanocomposite hydrogels were prepared by encapsulating green-synthesized polypyrrole (PPy) colloids within chondroitin sulfate (CS) networks during the self-crosslinking of CS via N-ethyl-N′-(3-dimethylaminopropyl) carbodiimide chemistry. The structural and morphological properties of CS/PPy hydrogels were studied by Fourier-transformed infrared spectroscopy, scanning electron microscopy, and swelling kinetic measurements. The chemotherapeutic agent 5-fluorouracil (5-FU) was loaded into CS/PPy samples by hydrogel swelling method, or alternatively, by pre-incubating the drug in polymer mixture before crosslinking. Different electrical stimulations can be used to switch ON and accurately tune the 5-FU delivery from GG/PPy hydrogels. A single pulse potential of 5 V switched on the drug delivery up to 90% from nanocomposite hydrogel, in contrast to the low 5-FU amount released in a passive form (< 20%). PPy electroactive behavior played a determining role as the main driving force in 5-FU release activation. Cytotoxicity of hydrogels with and without 5-FU was examined in normal and cancer cells. Considering the high cytotoxicity of 5-FU, the ON/OFF 5-FU release patterns evidenced the potential of CS/PPy hydrogels for electrically controlled drug delivery in implantable or transdermal drug release devices.     

Effect of polymer and ion concentration on mechanical and drug release behavior of gellan hydrogels using factorial design

Developing optimized hydrogel products requires an in-depth understanding of the mechanisms that drive hydrogel tunability. Here, we performed a full 4 × 4 factorial design study investigating the impact of gellan, a naturally derived polysaccharide (1%, 2%, 3%, or 4% w/v) and CaCl₂ concentration (1, 3, 7, or 10 mM) on the viscoelastic, swelling, and drug release behavior of gellan hydrogels containing a model drug, vancomycin. These concentrations were chosen to specifically provide insight into gellan hydrogel behavior for formulations utilizing polymer and salt concentrations expanding beyond those commonly reported by previous studies exploring gellan. With increasing gellan and CaCl₂ concentration, the hydrogel storage moduli (0.1–100 kPa) followed a power-law relationship and on average these hydrogels had higher liquid absorption capability and greater total drug release over 6 days. We suggest that the effects of gellan and CaCl₂ concentration and their interactions on hydrogel properties can be explained by various phenomena that lead to increased swelling and increased resistance to network expansion.     

Hydrophilic polymer drug from a derivative of salicylic acid: synthesis, controlled release studies and biological behavior

Hydrophilic polymeric drugs bearing "Triflusal" (4-trifluoromethylsalicylic acid), a drug widely used as antithrombogenic agent (Disgren), have been prepared by free radical copolymerization of methacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)] benzoate (HTRF) and N,N'-dimethylacrylamide (DMA). The reactivity ratios of both monomers have been determined by 1H NMR spectra by applying non-linear least square treatments to the copolymerization equation (terminal model), and the kinetic parameters obtained indicated that the microstructure of copolymer chains is homogeneous, with a random distribution of the active HTRF units along the copolymer chains. That means that for the copolymer system THDMA22 used in this work, HTRF units are mainly isolated in relatively long DMA sequences. Therefore, in this structure the intramolecular interactions between adjacent HTRF units are negligible. Release of Triflusal from THDMA22 has been studied in vitro using buffered solutions at pH = 2, 7.4 and 10 and 37 degrees C. The system showed an interesting pseudo-zero order release profile at pH = 7.4 during several months. It has been also evaluated the pharmacological activity and the behavior of the system in contact with biological media. In this sense, we have carried out some in vitro studies about the antiaggregant properties and biocompatibility of THDMA22. Results demonstrate that this copolymer inhibits platelet aggregation in its macromolecular form and presents a good biocompatibility with Human Osteoblastic Cells (HOS).     

Micelle-like macromolecular systems for controlled release of daunomycin

Soluble macromolecular conjugates for the delivery of the strongly hydrophobic anticancer drug daunomycin (DM) or rubomycin with its controlled release were prepared. The solution properties of these conjugates consisting of DM bonded to copolymer of maleic anhydride and divinyl ether (DIVEMA) and a few model compounds were investigated using adsorbance spectroscopy, as well as surface activity and solubilization of water-insoluble dye measurements. The data of these studies indicated that in water solutions conjugates are associated, probably intramolecularly. This micellization in parallel with an H-bonded ionic complex between DM and polymer carrier determines the DM release. It is concluded that the desirable drug release can be achieved through changing the structure of conjugates by means of varying the constituents hydrophobicity. © 1998 John Wiley & Sons, Ltd.     

PVA/P(AA-AM)水凝胶的制备及药物控制释放性能研究

以聚乙烯醇(PVA)、丙烯酸(AA)和丙烯酰胺(AM)为单体,过硫酸铵(APS)为引发剂、N,N'-亚甲基双丙烯酰胺(MBA)为交联剂,通过化学引发聚合制备互穿水凝胶PVA/P(AA-AM);用红外光谱(IR)、热重分析(TG)、差示扫描量热法(DSC)及扫描电镜(SEM)等测试方法对其进行了表征,并对其溶胀性能、p H敏感性以及离子强度对溶胀性能的影响进行了研究;并考察了该凝胶分别在p H=6.86和p H=1.80介质中对药物异烟肼和烟酸的控制释放行为。结果表明,PVA/P(AA-AM)水凝胶具有良好的p H、离子强度敏感性,在两种介质中异烟肼的累积释放率均高于烟酸,但异烟肼在p H=1.80的介质中的释放速度和累积释放率均高于其在p H=6.86的介质,烟酸则结果恰好相反。所以这种水凝胶有望用作靶向药物释放的载体。     

Preparation of albumin—PAA nanocapsules and their controlled release behavior for drugs

New kinds of narrowly distributed protein‐based nanoparticles, bovine serum albumin‐Poly (acrylic acid) (BSA/PAA) nanospheres, and nanocapsules were prepared via in situ polymerization, swelling, and re‐aggregation. The structure and morphology of the nanospheres were characterized by UV‐Vis, FT‐IR, DLS, and TEM. The stability of the BSA/PAA nanospheres and nanocapsules was increased when their skeletons were fixed by cross‐linked agents. The nanospheres carried a positive charge and their size was about 80–110 nm. The protein‐based nanocapsules were stimuli‐responsive with pH value and their hydrodynamic diameter varied from 70 to 230 nm with changes of pH. In vitro release experiments of Rhodamine B and Doxorubicin hydrochloride showed that these biopolymer nanoparticles provided a controlled release of the entrapped drugs for 300 hr. Copyright © 2009 John Wiley & Sons, Ltd.     

Loading and in vitro controlled release of indomethacin using amphiphilic cholesteryl-bearing carboxymethylcellulose derivatives

Amphiphilic CCMCs were synthesized under mild conditions and their chemical structures were characterized by FT-IR and 1H NMR spectroscopy. Fluorescence analysis showed that CCMCs could self-associate to form polymeric micelles in aqueous solution. IND was encapsulated during the formation of CCMC micelles and its in vitro release properties were investigated. The loading capacity was more than 50% and the loaded IND was slowly and steadily released into the medium over a period of 8 h. The CCMC micelles showed pH-responsive behavior during the drug-loading and release processes. CCMC is promising as a potential delivery system for the controlled release of IND with a pH-responsive property.