Ibuprofen grafted on poly(2-hydroxyethylmethacrylate): Synthesis,mass transfer,and in vitro drug release investigations

Poly(2-hydroxyethylmethacrylate-graft-ibuprofen) (IpGH) of different ibuprofen (Ibu) contents was prepared by grafting of Ibu groups on poly(2-hydroxyethyl methacrylate) (PHEMA) in an esterification reaction route. The resulted copolymers were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance, differential scanning calorimetry, thermal gravimetric analysis, X-ray diffraction, and scanning electron microscope analysis. The cytotoxicity test and the free radical scavenging ability of this material were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) and 1,1-diphenyl-2-picryl-hydrazyl assay methods, respectively. The in vitro release study of Ibu through a retro-esterification reaction of IpHG material during 3 days reveals that the release dynamic depends on the initial Ibu grafted, pH media, and the swelling degree of PHEMA. It was also revealed that the water solubility of Ibu easily reached a maximum of 0.216?mg?mL^?1. The diffusion of Ibu through the polymer matrix obeys the Fickian model. The estimated distribution of the cumulative drug released in different simulated digestive organs reveals that the IpHG7 containing 6.69?mol% of Ibu content showed the best performance.     

Microwave assisted synthesis of poly(2-hydroxyethylmethacrylate) grafted agar (Ag-g-P(HEMA)) and its application as a flocculant for wastewater treatment

Poly(2-hydroxyethylmethacrylate) chains were grafted onto the backbone of agar using a microwave assisted method involving a combination of microwave irradiation and ceric ammonium nitrate to initiate the grafting reaction. The synthesized graft copolymers were characterized by intrinsic viscosity measurements, Fourier transform infrared spectroscopy, elemental analysis (C, H, N, O and S) and scanning electron microscopy. Ag-g-P(HEMA)-2 showed a much higher flocculation efficacy than agar. The optimized dosage of flocculation for Ag-g-P(HEMA)-2 in the wastewater was found to be 0.75 ppm. Compared to agar, Ag-g-P(HEMA)-2 was found to considerably reduce the pollutant load in the wastewater.     

Preparation,characterization, and salicylic acid release behavior of chitosan/poly(vinyl alcohol) blend microspheres

Blend microspheres of chitosan (CS) with poly(vinyl alcohol) (PVA) were prepared as candidates for oral delivery system. CS/PVA microspheres containing salicylic acid (SA), as a model drug, were obtained using the coacervation‐phase separation method, induced by addition of a nonsolvent (sodium hydroxide solution) and then crosslinked with glutaraldehyde (GA) as a crosslinking agent. The microspheres were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy. Percentage entrapment efficiency, particle size, and equilibrium swelling degree of the microsphere formulations were determined. The results indicated that these parameters were changed by preparation conditions of the microspheres. Effects of variables such as CS/PVA ratio, pH, crosslinker concentration, and drug/polymer (d/p) ratio on the release of SA were studied at three different pH values (1.2, 6.8, and 7.4) at 37°C. It was observed that SA release from the microspheres increased with decreasing CS/PVA ratio and d/p ratio whereas it decreased with the increase in the extent of crosslinking. It may also be noted that drug release was much higher at pH 1.2 than that of at pH 6.8 and 7.4. The highest SA release percentage was obtained as 100% for the microspheres prepared with PVA/CS ratio of 1/2, d/p ratio of 1/2, exposure time to GA of 5 min, and concentration of GA 1.5% at the end of 6 h. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Poly(2-hydroxyethylmethacrylate-co-2-folate ethylmethacrylate) and Folic acid/Poly(2-hydroxyethylmethacrylate) Solid Solution: Preparation and Drug Release Investigation

Poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) was synthesized by free radical polymerization of 2-hydroxyethylmethacrylate with 2-folatethylmethacrylate and folic acid/poly(2-hydroxyethylmethacrylate) solid solutions was prepared by mixing folic acid with poly(2-hydroxyethylmethacrylate) using the solution casting method. The structure and the homogeneity distribution of folic acid in the polymer matrix are characterized by different methods. The diffusion behaviors of water and folic acid through poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) and poly(2-hydroxyethylmethacrylate) matrixes were found obey to the Fick models. The in vitro cytotoxicity assessed by microculture tetrazolium test assay and the antioxidant activity of poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) systems determined by 1,1-diphenyl-2-picryl-hydrazyl method revealed no significant toxicity of these systems and has excellent free radical scavenger property which can be as safe candidate in drug-carrier system. The solubility enhancement of folic acid in different pH media is also investigated and the results obtained reveal a maximum of 399–400?mg?L^?1. The release dynamic of folic acid from the poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) containing 5?mol% of folic acid and that from folic acid/poly(2-hydroxyethylmethacrylate) system containing 10?mol% of folic acid have the best intestine/stomach ratio.     

聚(乳酸-氨基酸)共聚物药物缓释载体微球的研究进展

介绍了丙交酯和氨基酸及其衍生物的共聚物——聚(乳酸-氨基酸)制备药物缓释微球的方法以及微球的结构特点,并详细介绍了微球粒径大小及分布、表面电荷、表面形貌及化学组成成分、药物包附及释放行为等性能的表征方法,展望了这种微球在药物控制释放体系和其它领域中的应用前景。     

Chitosan/poly(lactic acid) blends as drug delivery systems

Abstract

The immobilization and controlled release of salicylic acid (SA) in chitosan/poly(lactic acid) (Ch/LA) blends were studied in the present work. The Ch/PLA bland’s morphology was studied by SEM. FT-IR and DSC were used to investigate the interactions between the polymer matrix and the SA. The SA release kinetics was interpreted by the Weibull and Higuchi models. The SA release was the fastest in Ch/PLA systems with inhomogeneous and porous structure. It was slower in neat PLA matrix due to its dense structure and hydrophobic behavior, and in neat chitosan matrix, because of specific electrostatic chitosan/SA interactions and complex formation.     

Pectin grafted poly(N‐vinylpyrrolidone): Optimization and in vitro controllable theophylline drug release

The present article describes preparation, optimization, and characterization of pectin grafted polyvinylpyrrolidone hydrogels followed by controllable theophylline drug release. The gels were prepared in the presence of N,N′–methylenebisacrylamide (MBAA) crosslinker and ceric ammonium nitrate (CAN) initiator under N₂ atmosphere. Optimum conditions, in terms of percent of grafting (%G), were determined as follows: Pectin = 1.0 g, [NVP] = 2.81 mM, [MBAA] = 0.65 mM, [CAN] = 0.073 mM, polymerization temperature = 30°C and time = 4.0 hrs. Hydrogels were characterized by FTIR, TGA, DSC, XRD, and SEM. In vitro controllable release of theophylline model drug was studied using different N‐vinylpyrrolidone monomer to MBAA crosslinker ratio (i.e., [NVP]/[MBAA] ratios) and different polymerization temperatures at two pH values, namely 5.5 and 7.4. The optimum conditions for colon‐targeted vehicles that could provide the least theophylline release at pH 5.5, and the most theophylline release at pH 7.4, were as follows: [NVP]/[MBAA] = 4.33, polymerization temperature = 10°C and %G = 62.2. Such promising hydrogel characteristics may play the key role in many future drug release implementations. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

In vitro release of salicylic acid through poly(vinyl alcohol‐g‐itaconic acid) membranes

In this study, itaconic acid (IA) was grafted on poly(vinyl alcohol) (PVA) at two different grafting percentages, 7.0% (w/w) and 14.0% (w/w), and membranes were prepared from the grafted copolymer (PVA‐g‐IA). Performances of PVA and PVA‐g‐IA membranes for the transdermal release of salicylic acid (SA) at in vitro conditions were investigated by using 2.0 mg/mL SA solutions. Effect of the pH on the release of SA was studied by keeping pH of donor and acceptor solutions in a range of (2.1–7.4). Permeation studies were also carried on at different SA concentrations. Effect of temperature on the release of SA was investigated in the temperature range of (32–39) (±1)°C. Results showed that presence of IA decreased the release of SA from the PVA membranes and 73% SA was released at the end of 48 h at (32 ± 1)°C from the IA‐1 membranes. pH affected the release of SA through the grafted membranes and studies showed that release of SA was high with donor solution pH of 2.1. When the pH of donor and receiver solutions were kept at the same pH value, the overall SA% in permeate increased. Increase in concentration of SA decreased the release of SA for the studied membranes. Release of SA from PVA‐g‐IA membranes was temperature sensitive and increase in temperature from (32 ± 1)°C to (39 ± 1)°C increased the release percentage of SA by 24% (w/w). The overall activation energy for the permeation of SA through IA‐1 membrane was found to be 22.97 kJ/mol. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Short poly(phenylene vinylene) chains grafted poly(organophosphazene)

Brominated poly(bis(4-methylphenoxyphosphazene) was allowed to react with 1,4-bischloromethylbenzene or 1,4-bischloromethyl-2,5-dimethoxybenzene in solution using phase transfer catalyst or potassium t-butoxide. Poly(p-phenylene vinylene) or poly(2,5-methoxy-1,4-phenylene vinylene) grafted organophosphazene copolymers were obtained. The UV-Vis absorption, photoluminescent, and thermal properties of the copolymers were measured. The copolymers are complete soluble in common organic solvents and fluoresce in the blue color range. The copolymers were used to build a series of organic light emitting diode (OLED). Only weak to nominated intensities with emission color from blue to red were obtained. The photoluminescent and electroluminescent (EL) spectra indicated there is a distribution in the PPV conjugated length. The compositions of the copolymers before and after the graft reaction were analyzed using NMR.     

Controlled release of fluorouracil (5-FU) from chitosan-co-poly(ethylene glycol)/ poly(glycerol sebacate)-co-poly(ethylene glycol)-coated iron oxide

A blend of polyglycerol sebacate-poly ethylene glygol/chitosan-poly ethylene glycol-coated iron oxide (PGS-PEG/CS-PEG@Fe₃O₄) nanoparticles for 5FU delivery was prepared by reverse ultrasonic emulsification method. To enhance polymers’ solubility, PEG was grafted. Chemical characterization was performed through Fourier transformed infrared and proton nuclear magnetic resonance spectra. In vitro assay revealed that release profile of 5FU-loaded PGS-PEG/CS-PEG@Fe₃O₄ is sustained. Moreover, cytotoxicity was analyzed on HT29 cell line at the presence of external magnetic field using the lactate dehydrogenase and Alamar Blue. Results illustrate that (PGS-PEG/CS-PEG@Fe₃O₄) is promising to use as a carrier for 5FU anticancer agent with sustained tailored release.     

温敏聚N-异丙基丙烯酰胺的载药和释药性能研究

以对乙酰氨基酚为模型药物分子,温敏水凝胶聚N-异丙基丙烯酰胺(PNIPAAm)为载体,研究了药物在凝胶上的负载和在不同温度(25和37℃)下磷酸盐缓冲溶液(pH 7.4)中的释放行为.结果表明,对乙酰氨基酚的负载量约为35wt％,并且与载体PNIPAAm存在氢键作用.药物在磷酸盐缓冲溶液中的体外模拟释放结果显示,当温度(37℃)高于凝胶的LCST时,对乙酰氨基酚释放的较慢;当温度(25℃)低于其LCST时,释放的较快.因此,可通过环境温度的改变达到APAP在载体PNIPAAm上控制释放的目的.     

Thermosensitive soy protein/poly(n‐isopropylacrylamide) interpenetrating polymer network hydrogels for drug controlled release

A series of the thermosensitive interpenetrating polymer network hydrogels composed of soy protein and poly(N‐isopropylacrylamide) were successfully prepared. The structure and properties were systematically characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and differential scanning calorimetry. It was found that the hydrogels had good miscibility and high porosity, and the volume phase transition temperatures of the hydrogels were around 32°C. The release behavior and the release mechanism of a model protein, bovine serum albumin (BSA), were also investigated in detail. The results indicated that the release behavior of BSA had strong temperature dependence and the release percentage of BSA could be controlled by modulating the amount of soy protein or crosslinking agent. The analysis of the release mechanism revealed that the Fickian diffusion controlled release was dominant under the experimental conditions. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011.     

Comparison of poly(aspartic acid) hydrogel and poly(aspartic acid)/gelatin complex for entrapment and pH‐sensitive release of protein drugs

Biodegradable poly(aspartic acid) (PASP) hydrogel and PASP/gelatin complex were prepared to evaluate their potential application as pH‐sensitive matrices for controlled protein release. Entrapment of myoglobin (Mb) and its release were compared between the two types of carriers. It was found that incorporation of Mb into PASP hydrogel strongly depended on the medium pH and NaCl concentration, and was time‐consuming. However, complete entrapment of Mb into PASP/gelatin complex was found within pH ranged from 2.5 to 4.0, which was concomitant with the formation of PASP/gelatin complex. By adjusting Mb feed ratio, Mb entrapment in the complex can be up to 31.54% (by weight) with high loading efficiency (96.2%). Gradual release of Mb from PASP hydrogel was observed within pH 2.0–7.4, while Mb release from PASP/gelatin complex was negligible within pH 2.0–4.2 for 4 days. In addition, pulsatile Mb release can be achieved by combining polyanhydride with pH‐sensitive PASP/gelatin complex, while the device composed of polyanhydride and PASP hydrogel is mechanically unstable. PASP/gelatin complex formed by electrostatic interactions is superior to the single‐component PASP hydrogel synthesized by chemical cross‐linking as pH‐sensitive matrices for controlled protein release when entrapment of proteins and pH‐sensitivity of protein release are concerned. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006     

Diffusion and controlled release characteristics of pH-sensitive poly(2-(dimethyl amino)ethyl methacrylate-co-2-hydroxyethylacrylate) hydrogels

The authors describe a facial development of pH-responsive hydrogels composed of 2-(dimethylamino)ethylmethacrylate and 2-hydroxyethylacrylate via free-radical polymerization at 29°C. The hydrogels were characterized by FTIR, SEM, and XRD studies. The diffusional exponent (n), hydrogel network parameters such as average molecular weight between crosslinks (M_c), and polymer-solvent interaction (χ) were calculated by using swelling data. The hydrogels were encapsulated with 5-fluorouracil, the in vitro release data indicated that the maximum drug release was significantly achieved in pH 1.2 rather than in pH 7.4 and it was enhanced up to 30 h. These results suggested that the gels are highly useful for anticancer drug delivery applications.     

Controlled release of methylene blue from layer-by-layer assembled chitosan/polyacrylic acid

Abstract

The electrostatic layer-by-layer (LbL) assembled multilayer films were widely used in the biomedical technology such as drug delivery. In this work, loading capabilities and release behavior of the multilayer films chitosan (Cts) and poly(acrylic acid) (PAA) were studied. The multilayer films were assembled by LbL technique through alternating deposition of Cts and PAA on glass slides, using methylene blue (MB) as a model drug. All the results showed that the LBL film’s loading and release efficiency greatly controllable by pH and ionic strength of the solution. It suggested that the Cts/PAA LBL film had potential applications in drug delivery and controlled release studies.     

Miscibility of poly(acrylic acid)/poly(methyl vinyl ketone) blend and in vitro application as drug carrier system

A series of poly(acrylic acid)/poly(methyl vinyl ketone) (PAA/PMVK) blends with different compositions were prepared by the solvent casting method. The miscibility of this pair of polymers was investigated by differential scanning calorimetry(DSC), Fourier transform infra-red (FTIR) and X-Ray diffraction (XRD) techniques. An in-vitro cytotoxicity test of the drug-carrier system via MTT (3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay revealed no significant cytotoxic effects at concentrations up to 100 µg· ml^?1. The STX/PAA-50 drug carrier systems were also prepared by solvent casting of solutions containing the sulfamethoxazole (STX) used as drug model and PAA/PMVK blend in N.N-dimethylformamide then crosslinked with acidified ethylene glycol. The release dynamic of STX from the prepared hydrogels was investigated in which the diffusion through the polymer matrix, the enhancement of the water solubility of STX, the influence of the initial drug concentration, the pH of the medium, and the effect of the degree of swelling of the polymer matrix on the release dynamic was evaluated. According to the total gastrointestinal transit time estimated by Belzer, the estimate distribution of STX released in the different organs indicated that the performance is obtained with the drug – carrier-system containing equal ratios of polymer and 10 wt% of STX (STX-10/PAA-50).     

The adsorption of Cu(II) ion from aqueous solution upon acrylic acid grafted poly(ethylene terephthalate) fibers

This study is concerned with the investigation of the adsorption properties of acrylic acid grafted poly(ethylene terephthalate) fibers by the use of Cu(II) ions in aqueous solutions. Influence of pH, graft yield, contact time, concentration of the ion, and reaction temperature on the amount of ion adsorbed upon reactive fiber were investigated. The time in which the adsorption reached to the equilibrium value was determined as 1 h. The adsorption isotherm of Cu(II) ion was found to be a Langmuir type and the heat of adsorption was calculated as ?10.1 kJ mol^?1. It was observed that the adsorbed Cu(II) ion upon acrylic acid grafted poly(ethylene terephthalate) fibers could be recovered in acidic media. The fiber could also readsorb Cu(II) ions without losing its activity. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1216–1220, 2003     

Controlled release of nonionic compounds from poly(lactic acid)/cellulose nanocrystal nanocomposite fibers

Poly(lactic acid)(PLA)/cellulose nanocrystal nanocomposite fibers were prepared by electrospinning at elevated temperature. Columbia Blue, a nonionic hydrophobic dye with a molecular weight and partition coefficient that mimics a systemic agrichemical, was incorporated into the fibers as a model compound. The release of Columbia Blue into water displayed little burst release. Diffusion‐controlled release of Columbia Blue was significantly influenced by the hydrophobicity of the electrospun PLA nanocomposite fibers and followed Fickian diffusion kinetics. The release of Columbia Blue by degradation‐controlled mechanism followed zero‐order, time‐independent Case II kinetics (n = 1.0). Increasing cellulose nanocrystal content in the fibers increased the fiber degradation rate and the Columbia Blue release rate. The plasticizing effect of Columbia Blue on the thermal properties of the electrospun nanocomposite fibers showed the miscibility of Columbia Blue inside the electrospun nanocomposite fibers. A greenhouse trial confirmed the anticipated trends of higher pesticide dosage causing higher whitefly mortality percentage. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2013     

Application of 2-hydroxyethyl methacrylate polymers in controlled release of 5-aminosalicylic acid as a colon-specific drug

Acrylic type polymeric systems having degradable ester bonds linked to 5-aminosalicylic acid were synthesized and evaluated as materials for drug delivery. 5-Aminosalicylic acid, as an important drug in the treatment of inflammatory bowel diseases, was linked to 2-hydroxyethyl methacrylate by activated ester methodology in two-step and one-pot procedures to obtain methacryloyloxyethyl 5-amino salicylate. The resulting methacrylic derivative of 5-aminosalicylic acid was copolymerized with methacrylamide, 2-hydroxyethyl methacrylate and methyl methacrylate (in 1:3 mole ratio) by free radical polymerization method in N,N-dimethylformamide solution, utilizing α,ά-azoisobutyronitrile as initiator at the temperature range of 65–70 °C. The obtained polymers were characterized by FT-IR, ¹H NMR, ¹³C NMR and elemental analysis. The average molecular weights of the polymers bearing drug units as side substituents of the acrylic backbone were determined by gel permeation chromatography and their polydispersity indices resulted in the range of 1.6–1.8. Release studies of 5-aminosalicylic acid were performed into dialysis bags by hydrolysis in buffered solutions (pH 1, 7 and 8) at 37 °C. Detection of hydrolysis by UV spectroscopy at selected intervals showed that the drug can be released by selective hydrolysis of the ester bond at the side of drug moiety. The release profiles indicated that the hydrolytic behavior of polymeric prodrugs is strongly based on the polymer hydrophilicity and the pH value of the hydrolysis solution. The results suggest that these systems could be useful for preparation of a controlled release formulation of 5-aminosalicylic acid in colon.     

Drug release from poly(ortho esters)–poly(ethylene glycol) polyblend

A polyblend of poly(ortho esters)–poly(ethylene glycol) (POE–PEG) was prepared. The release behavior of the acetanilide‐loaded film of the POE–PEG polyblend was studied. Blending POE with water‐soluble PEG can promote the release of drug in pH 7.4 PBS buffer at 37°C, while POE has plasticizing effect on PEG. Infrared and X‐ray diffraction studies reveal that there is some interaction between POE and acetanilide. The SEM micrographs disclose that the porosity of the drug‐loaded film enhances with an increase immersing time. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 303–309, 1999