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.     

Preparation and characterization of the poly(2-hydroxyethyl methacrylate)–salicylic acid conjugate

A new polymeric system containing hydrolysable ester bond linked to salicylic acid to be used for controlled drug release was synthesized. Poly(2-hydroxyethyl methacrylate) (PHEMA) functionalized with chloroacetate groups was obtained by the reaction between PHEMA and chloroacetyl chloride using the N,N-dimethylacetamide/5% lithium chloride system as a solvent and pyridine as a catalyst. The degree of substitution was calculated from the chlorine content and ranged from 32.2 to 98.1 mol.% depending on the ratio of chloroacetyl chloride to PHEMA. The coupling of salicylic acid to PHEMA functionalized with chloroacetate groups was carried out by the reaction between PHEMA and the sodium salt of salicylic acid. The structures of chloroacetylated PHEMA and PHEMA–salicylic acid conjugates were determined by means of FTIR, ¹H-NMR and ¹³C-NMR spectra. The hydrolysis in the heterogeneous system of PHEMA–salicylic acid conjugates were performed in buffer solutions (pH 7.6 and 8.5) at 37 °C and showed that the release of the drug (sodium salicylate) from tablets was dependent on the hydrophilic character of conjugate as well as on the pH value of the medium.     

Polymer micellar aggregates of novel amphiphilic biodegradable graft copolymer composed of poly(aspartic acid) derivatives: Preparation,characterization, and effect of pH on aggregation

Novel amphiphilic biodegradable graft copolymer based on poly(aspartic acid) was prepared by attaching monomethoxy polyethylene glycol (mPEG) as hydrophiphic segment to poly(aspartic acid‐g‐octadecylamine) (PASP‐g‐ODA) as hydrophobic backbone. The chemical structures of amphiphilic copolymers were confirmed by FTIR and ¹H NMR spectroscopy. The polymeric micelles were prepared with solvent evaporation and their physicochemical properties in aqueous media were characterized by dynamic light scattering (DLS) and fluorescence spectroscopy. These micelles were confirmed to be pH‐sensitive by measuring optical transmittance of micelle solution and the size of micellar aggregates. The number average diameter of polymeric micelles prepared in medium at pH 2.5 was larger than that in neutral and basic medium and showed a bimodal size distribution because of the protonation of carboxyl groups in backbone. Furthermore, the polymeric micelle can load water‐insoluble drug (podophyllotoxin), and the drug release from micelles showed a pH‐dependency. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006     

Modification of Starch by Grafting Acetylsalicylic Acid: Synthesis,Characterization, and Application in Drug Release Domain

A series of modified starches were prepared by grafting acetylsalicylic acid (AsA) into starch by an esterification reaction then coated with poly(vinylalcohol).The structure of Starch-graft-AsA was confirmed by FTIR, NMR, and DSC. The release of AsA occurred via a retroesterification reaction of this modified coated starch (SAC) during 76 h at different pHs and AsA contents. The diffusion coefficient of AsA in the SAC matrix followed a Fickian model. The effect of AsA amount grafted on starch revealed that the higher AsA amount released was reached with SAC containing 16.18 mol% of AsA at pH 7.     

Synthesis,Characterization, and Release Dynamic of Acetylsalicylic Acid From Acetylsalicylic Acid/Poly(vinylalcohol-co-ethylene) Membrane

A series of poly(vinylalcohol-co-ethylene)/acetylsalicylic acid blends (PEVA/AcSa) of different AcSa contents were prepared and characterized by the solubility test, differential scanning calorimetry, and scanning electron microscopic analyses. The results revealed that AcSa was perfectly soluble in PEVA at certain composition and uniformly distributed throughout the polymer matrix. The release dynamic of AcSa from PEVA/AcSa material was studied at body temperature during 92 h in which the influence of AcSa initially incorporated in PEVA, the pH of media, the membrane thickness, and the stability of AcSa release rate on the release dynamic were detailed.     

Synthesis and characterization of poly(2-hydroxyethyl methacrylate)-1-naphthylacetic acid adduct

Summary Poly(2-hydroxyethyl methacrylate) (PHEMA) functionalized with chloroacetate groups was obtained by reaction of PHEMA with chloroacetyl chloride using the 5% lithium chloride/N,N-dimethylacetamide system as solvent and pyridine as catalyst. The coupling of bioactive carboxylic acid (1-naphthylacetic acid) to PHEMA functionalized with chloroacetate groups was carried out by reaction with its the potassium salt. The structures of chloroacetylated PHEMA and PHEMA-1-naphthylacetic acid adducts were determined by means FTIR, ¹H-NMR and ¹³C-NMR spectra. The degree of substitution was calculated from the chloride content and ranged from 13.4 to 98.1 mol% depending on the ratio of chloroacetyl chloride to PHEMA. The hydrolysis in the heterogeneous phase of PHEMA-1-naphthylacetic acid adducts showed that the release of the bioactive compound from tablets is dependent on hydrophilic character of adduct as well as on pH value of the medium.     

l-Ascorbic acid release from phema hydrogels

Controlled release of L-ascorbic acid from poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels is reported. PHEMA hydrogels were synthesized from 2-hydroxyethyl methacrylate (HEMA) monomer in an oven. We studied the swelling of PHEMA discs in water as a fuction of temperature and thickness of xerogel discs. The fractional swelling was linear in (time)^1/2 at short times. Drug release has been examined as a fuction of temperature, initial drug load and thickness of the PHEMA discs. The fraction of avaible drug release was linear in (time)^1/2 during the initial stage too. The release experiments were carried out at 308 K. These studies allow to determinate a diffusion coefficient for transport of water into the hydrogels and a diffusion coefficient for L-ascorbic acid release from the hydrogel.     

Amphiphilic biodegradable poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) triblock copolymers: synthesis, characterization and their use as drug carriers for folic acid

Amphiphilic biodegradable poly(ε-caprolactone)-poly(ethylene glycol)-poly (ε-caprolactone) (PCEC) triblock copolymers have been successfully synthesized by the ring-opening polymerization of ε-caprolactone (ε-CL) employing SnOct as catalyst and double-hydroxyl capped PEG (DHPEG) as macro-initiator. The triblock structure and copolymer composition were conformed by FT-IR, ¹H-NMR, and GPC. Using a membrane dialysis method, PCEC micelles were prepared with a core–shell type. The critical micelle concentration (CMC) of PCEC triblock copolymers was determined by fluorescence technique using pyrene as probe, and CMC values decreased with the increase of PCL chain length. From the observation of transmission electron microscopy (TEM), the morphology of polymer micelles was spherical in shape. Micelles size measured by dynamic light scattering (DLS) exhibited a narrow size distribution. Folic acid (FA) was then used as a model drug to incorporate into PCEC micelles. The diameter, drug loading, and drug release rate of PCEC micelles were influenced by the feed weight ratio of FA and copolymer, and polymer composition. In addition, in vitro release experiments of the drug-loaded PCEC micelles exhibited sustained release behavior without any burst effects and the release behavior was also affected by the pH of release media.     

Free‐radical polymerization of urea,acrylic acid,and glycerol in aqueous solutions

The main objective of the present study is to produce copolymers of urea, acrylic acid, and glycerol through aqueous solution free‐radical polymerizations and analyze the structural, thermal, rheological, and release properties of the obtained materials. To do this, aqueous solution copolymerizations were performed in different reaction conditions and the obtained copolymers were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, rheological analyses, thermogravimetry, gel permeation chromatography, and rates of urea release in distilled water. The obtained results indicate that all constituents of the reacting mixture (potassium persulfate, glycerol, urea, and acrylic acid) affect the characteristics of the produced copolymers. In particular, it is shown that urea can be incorporated into the final copolymer through the proposed reaction scheme, that glycerol promotes crosslinking of polymer chains and that the obtained copolymer materials can be used in agricultural applications. POLYM. ENG. SCI., 55:1219–1229, 2015. © 2015 Society of Plastics Engineers     

Preparation of poly(butylene succinate)‐poly[2‐(dimethylamino)ethyl methacrylate] copolymers and their applications as carriers for drug delivery

Copolymers of poly[2‐(dimethylamino)ethyl methacrylate]–poly(butylene succinate)–poly[2‐(dimethylamino)ethyl methacrylate] (PDMAEMA–PBS–PDMAEMA, PDBD) were synthesized through a chain‐extension reaction. The thermal properties characterized using differential scanning calorimetry showed that the introduction of PDMAEMA chains slightly decreased the melting temperature of PBS. The water contact angle of PDBD copolymer films with media of various pH decreased with a decrease of pH. This should be ascribed to the conformational transition of PDMAEMA blocks from a compact coil to an expanding shape in accordance with the variation of the pH of the surroundings. The results of dynamic light scattering and scanning electron microscopy revealed that PDBD copolymers could form spherical micelles with small particle size and narrow particle size distribution. Furthermore, drug loading (loading content, ca 10%; encapsulation efficiency, ca 60%) and release experiments were conducted using doxorubicin as a hydrophobic model drug. The results of release experiments of copolymer nanomicelles showed that these micelles had pH‐responsive properties. © 2018 Society of Chemical Industry     

Synthesis of pH‐responsive polyethylene terephthalate track‐etched membranes by grafting hydroxyethyl‐methacrylate using atom‐transfer radical polymerization method

pH‐responsive polyethylene terephthalate (PET) track‐etched membranes were synthesized by grafting 2‐hydroxyethyl‐methacrylate (HEMA) on the surface of the membrane via atom transfer radical polymerization. The controllability of grafting polymerization of HEMA on membrane surface is systematically investigated. The pH‐responsive characteristics of PET‐g‐poly(2‐hydroxyethyl‐methacrylate) (PHEMA) gating membranes with different grafted PHEMA chain lengths are measured by tracking the permeation of water solution with different pH values. The results show that the grafting polymerization is controllable, and the permeation of grafted membranes is affected by the grafted PHEMA chain lengths on the surface of membrane. The results also demonstrate that the grafted PET membranes exhibit reversible pH‐response permeation to environmental pH values. Desired pH‐responsive membranes are obtained by controlling the grafted PHEMA chain lengths via atom transfer radical polymerization method. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40912.     

Adsorption mechanism of fulvic acid onto freeze dried poly(hydroxo aluminum) intercalated bentonites

Two poly(hydroxo aluminum) intercalated Wyoming bentonites were prepared starting from two different aluminum pillaring solutions. The sorption mechanism of Laurentian fulvic acid (FA) onto these poly(hydroxo aluminum) intercalated bentonites was investigated at different pH values and at different ionic strengths (NaCl or CaCl₂). Three mechanisms contribute to the FA adsorption, depending on the pH and the nature (NaCl or CaCl₂) and ionic strength of the background electrolyte. In the presence of NaCl the FA sorption onto poly(hydroxo aluminum) intercalated bentonites can be mainly ascribed to ligand exchange between the amphoteric poly(hydroxo aluminum) hydroxyl groups and the deprotonated carboxylic groups of the FA. The FA adsorption due to ligand exchange reactions decreases with increasing pH. In presence of Ca²⁺ ions the FA adsorption is enhanced, compared to the presence of Na⁺, due to Ca²⁺ bridging between negatively charged groups on the FA molecules and the poly(hydroxo aluminum) intercalated bentonite. The FA adsorption due to Ca²⁺ bridging increases with increasing pH. A third mechanism is enhanced FA adsorption ascribed to FA-Ca-FA bridging and was detected from the FA adsorption in presence of Ca²⁺ at the zero point of charge of the poly(hydroxo aluminum) bentonite (pH 5).     

Comparison of thermomechanical properties of statistical, gradient and block copolymers of isobornyl acrylate and n-butyl acrylate with various acrylate homopolymers

Well-defined statistical, gradient and block copolymers consisting of isobornyl acrylate (IBA) and n-butyl acrylate (nBA) were synthesized via atom transfer radical polymerization (ATRP). To investigate structure-property correlation, copolymers were prepared with systematically varied molecular weights and compositions. Thermomechanical properties of synthesized materials were analyzed via differential scanning calorimetry (DSC), dynamic mechanical analyses (DMA) and small-angle X-ray scattering (SAXS). Glass transition temperature (T_g) of the resulting statistical poly(isobornyl acrylate-co-n-butyl acrylate) (P(IBA-co-nBA)) copolymers was tuned by changing the monomer feed. This way, it was possible to generate materials which can mimic thermal behavior of several homopolymers, such as poly(t-butyl acrylate) (PtBA), poly(methyl acrylate) (PMA), poly(ethyl acrylate) (PEA) and poly(n-propyl acrylate) (PPA). Although statistical copolymers had the same thermal properties as their homopolymer equivalents, DMA measurements revealed that they are much softer materials. While statistical copolymers showed a single T_g, block copolymers showed two T_gs and DSC thermogram for the gradient copolymer indicated a single, but very broad, glass transition. The mechanical properties of block and gradient copolymers were compared to the statistical copolymers with the same IBA/nBA composition.     

Preparation and characterization of proton‐conducting crosslinked diblock copolymer membranes

The synthesis and properties of crosslinked diblock copolymers for use as proton‐conducting membranes are presented. A polystyrene‐b‐poly(hydroxyl ethyl methacrylate) diblock copolymer at 56 : 44 wt % was sequentially synthesized via atom transfer radical polymerization. The poly(hydroxyl ethyl methacrylate) (PHEMA) block was thermally crosslinked by sulfosuccinic acid (SA) via the esterification reaction between  OH of PHEMA and  COOH of SA. Proton nuclear magnetic resonance and Fourier transfer infrared spectra revealed the successful synthesis of the diblock copolymer and the crosslinking reaction under the thermal condition of 120°C for 1 h. The ion‐exchange capacity continuously increased from 0.25 to 0.98 mequiv/g with increasing SA concentration because of the increasing number of charged groups in the membrane. However, the water uptake increased up to an SA concentration of 7.6 wt %, above which it decreased monotonically (maximum water uptake ∼ 27.6%). The membrane also exhibited a maximum proton conductivity of 0.045 S/cm at an SA concentration of 15.2 wt %. The maximum behavior of the water uptake and proton conductivity with respect to the SA concentration was considered to be due to a competitive effect between the increase of ionic sites and the crosslinking reaction according to the SA concentration. All the membranes were thermally quite stable at least up to 250°C, presumably because of the block‐copolymer‐based, crosslinked structure of the membranes. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2008     

Architecture of rod consisting of hyperbranched pendant chains‐coil block copolymers by ATRP approach

Atom transfer radical polymerization (ATRP) was applied to a novel synthesis of rod consisting of hyperbranched pendant chains‐coil block copolymers. The procedure included the following steps: (1) esterification reaction of poly(ethylene glycol) methyl ether (PEO) with 2‐bromoisobutyryl bromide (BIBB) yielded a PEO‐Br macroinitiator, (2) ATRP method of 2‐hydroxylethyl methacrylate (HEMA) using PEO‐Br provided PEO‐block‐poly(2‐hydroxyethyl methacrylate) (PHEMA) block copolymers, (3) esterification of PEO‐block‐PHEMA with BIBB yielded block‐type polyinitiator, and (4) ATRP of HEMA‐Br inimer using block‐type polyinitiator provided coil‐rod (consisting of hyperbranched pendant chains) block copolymers. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Enzymatic synthesis,thermal and crystalline properties of a poly(β–amino ester) and poly(lactone-co-β–amino ester) copolymers

Ethyl 3-(4-(hydroxymethyl)piperidin-1-yl)propanoate (EHMPP) was prepared in quantitative yield under mild conditions via Michael addition reaction of 4-piperidinemethanol with ethyl acrylate. EHMPP underwent condensation polymerization in the presence of a lipase catalyst (CALB) to form poly[3-(4-(methylene)piperidin-1-yl)propanoate] (poly(MPP) or PMPP). Ring-opening and condensation copolymerization of EHMPP with ω-pentadecalactone (PDL) led to the synthesis of novel poly(PDL-co-MPP) copolymers, whose compositions were readily controlled by varying the monomer feed ratio. NMR analyses, including statistical analysis on repeating unit sequence distribution, indicate that the copolymers are totally random polymers. TGA analysis revealed that the degradation temperature of PMPP is approximately 160 °C lower than that of PPDL and that all poly(PDL-co-MPP) copolymers degrade in two well defined weight loss steps attributable to thermal degradation of MPP and PDL unit fractions in the polymers. The crystallinity of the polymers was studied by DSC analysis. Although PMPP and the copolymers rich in MPP units do not easily crystallize upon cooling from melt, the homopolymer and all copolymers obtained via precipitation from solution are semi-crystalline materials. WAXS analysis showed that the copolymers rich in PDL (≥51 mol%) crystallize in PPDL lattice and those with ≤21 mol% PDL content develop PMPP-type crystals while in the copolymer with 36 mol% PDL, PMPP-type and PPDL-type crystals co-exist. PMPP and poly(PDL-co-MPP) represent a new type of biodegradable poly(β–amino esters) that are potentially useful biomaterials for specific biomedical applications (e.g., gene delivery).     

Structure and swelling of poly(acrylic acid) hydrogels: effect of pH, ionic strength, and dilution on the crosslinked polymer structure

The network formation of crosslinked polymer hydrogels made via a free radical polymerization mechanism is significantly influenced by the polymerization conditions. In particular, the crosslinked structure of ionic networks like poly(acrylic acid) copolymers is affected by the monomer concentration, the pH, and ionic strength during the polymerization. In this work experimental data as well as theoretical analysis are used to investigate how these factors control the degree of crosslinking and primary cyclization during the network formation of multifunctional monomers. It was found that the amount of water present during the polymerization increases primary cyclization rates, and this change affects the subsequent swelling behavior of the acrylic acid hydrogel. The effects of ionic strength and pH on the network structure are interrelated. An increase in the pH decreases the degree of primary cyclization while an increase in the ionic strength increases cyclization. To investigate further the effect of pH, a cationic polymer was formed that contained a monovinyl amine monomer and a novel diamine crosslinking agent synthesized in our laboratory. The combined effect of the ionizing backbone chain and crosslinking agent cause the degree of primary cyclization in this material to be extremely sensitive to the pH during polymerization. This result confirms the significant role of pH on the network formation in ionic materials.     

Temperature and pH effects on the stability and rheological behavior of the aqueous suspensions of smart polymers based on N‐isopropylacrylamide,chitosan, and acrylic acid

This study describes the stability and rheological behavior of suspensions of poly(N‐isopropylacrylamide) (PNIPAM), poly(N‐isopropylacrylamide)‐chitosan (PNIPAM‐CS), and poly(N‐isopropylacrylamide)‐chitosan‐poly(acrylic acid) (PNIPAM‐CS‐PAA) crosslinked particles sensitive to pH and temperature. These dual‐sensitive materials were simply obtained by one‐pot method, via free‐radical precipitation copolymerization with potassium persulfate, using N,N′‐methylenebisacrylamide as a crosslinking agent. Incorporation of the precursor materials into the chemical networks was confirmed by elementary analysis and infrared spectroscopy. The influence of external stimuli such as pH and temperature, or both, on particle behavior was investigated through rheological measurements, visual stability tests, and analytical centrifugation. The PNIPAM‐CS particles showed higher stability in acid and neutral media, whereas PNIPAM‐CS‐PAA particles were more stable in neutral and alkaline media, both below and above the lower critical solution temperature of PNIPAM (stability data). This is due to different interparticle interactions as well as those between the particles and the medium (also evidenced by rheological data), which were also influenced by the pH and temperature of the medium. Based on the results obtained, we found that the introduction of pH‐sensitive polymers to crosslinked PNIPAM particles not only produced dual‐sensitive materials but also allowed particle stability to be adjusted, making phase separation faster or slower, depending on the desired application. Thus, it is possible to adapt the material to different media. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Poly(benzoxazine-co-urethane)s: A new concept for phenolic/urethane copolymers via one-pot method

Historically, applications for traditional phenolic resin/polyurethane materials are limited due to the inherently weak thermal stability of urethane-phenolic linkage and slow reaction rate. A novel concept has been developed to produce phenolic resin/polyurethane copolymers via benzoxazine chemistry. Through one-pot synthesis, a series of linear poly(benzoxazine-co-urethane) materials has been synthesized via the reaction of a newly developed dimethylol functional benzoxazine monomer with 4,4′-methylene diphenyl diisocyanate and poly(1,4-butyleneadipate). The structure of the copolymers has been characterized by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). The copolymers in the film forms have been further thermally treated for crosslinking to produce crosslinked poly(benzoxazine-co-urethane) via the ring opening polymerization of cyclic benzoxazine moieties in the main-chain. The tensile properties of the films have been studied and compared with those of traditional high performance materials. The thermal properties of the crosslinked copolymers have also been studied by dynamic mechanical analysis, and thermogravimetric analysis (TGA).     

Low molecular weight polyacrylic acid with pendant aminomethylene phosphonic acid groups

Low molecular weight poly(acrylic acid‐co‐vinyl aminomethylene phosphonic acid)s were prepared by consecutively applying the Hofmann degradation and the Mannich reaction to polyacrylamide and poly(acrylamide‐co‐acrylic acid)s. ¹H‐NMR, ³¹P‐NMR, and microanalysis were used for structural analyses. These polymers were tested as anti‐scalent and they showed better anti‐scalent effect than commercial poly(acrylic acid)s. The scale inhibition properties of copolymers increased with increasing amount of aminomethylene phosphonic acid groups. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 870–874, 2000