Synthesis and characterization of a redox‐initiated,injectable, biodegradable hydrogel

A chemically crosslinked biodegradable hydrogel was prepared via a macromer technique, and physicochemical characterizations associated with its potential application as an injectable biomaterial were carried out. The macromers were composed of poly(ethylene glycol) extended with oligomers of biodegradable polyesters such as oligolactide and end‐capped with acryloyl groups. Hydrogels were obtained through the polymerization of the macromer aqueous solutions in phosphate‐buffered saline initiated by a redox initiator system at body temperature. The initiator system was composed of ammonium persulfate as an initiator and N,N,N′,N′‐tetramethylethylene diamine as an accelerator. The modulus of this chemical gel was much higher than that of a Pluronic physical gel. In vitro biodegradation was also confirmed. The degradation rates were highly tunable by the adjustment of several factors, such as the kind of ester group, the block length of the oligoester, and even the concentration of the accelerator used in the crosslinking reaction. The gelation time could be adjusted to meet the requirements of an injectable biomaterial. The effect of the polymerization heat seemed not to be significant. This kind of biodegradable hydrogel might be in situ formed after being injected into the body and shows potential applications as a unique tissue engineering material free of porogening techniques in scaffold fabrication and less invasive in implantation. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006     

Synthesis and characterization of a novel biodegradable polymer poly(lactic acid–glycolic acid‐4‐hydroxyproline)

The effect of certain preparative variables, such as the composition of the feeds, the reaction time, catalyst concentration, degrees Centigrade (°C), and the reaction temperature on the properties of prepared polymer poly(lactic acid–glycolic acid‐4‐hydroxyproline) (PLGA‐Hpr), was investigated via direct melt polymerization with stannous chloride as a catalyst activated by a proton acid. The new polymer had pendant amine functional groups along the polymer backbone chain. The results with regard to the inherent viscosity and yield of PLGA‐Hpr are discussed in relation to a recently proposed polymerization mechanism. The content of lactic acid, glycolic acid, and 4‐hydroxyproline (Hpr) in the copolymer was found to affect the surface and bulk hydrophilicity of various PLGA‐Hpr copolymers. The inherent viscosity of the copolymer and the yield of the reaction depended on the reaction temperature and varied with the reaction time. The higher the 4‐hydroxyproline content of the feedzaq, the lower the inherent viscosity of the copolymer and the yield of the reaction. When the glycolic acid content was more than 70% or the content of HPr was more than 10%, the polymer changed from hemicrystalline to amorphous. The in vitro degradation rate of the PLGA‐HPr copolymers is dependent on the feed ratios of lactic acid and glycolic acid in the polymer chain. Lactic acid‐rich polymers are more hydrophobic; subsequently they degrade more slowly. The structure of this polymer was verified by infrared (IR) spectroscopy, proton nuclear magnetic resonance (¹H‐NMR) spectroscopy, X‐ray diffractometry (XRD), and differential scanning calorimetry (DSC). © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3585–3590, 2007     

Synthesis and characterization of biodegradable and charged salen‐based polymers

The goal of this study was to synthesize novel biodegradable charged polymers for medical applications. The polymers synthesized were metal‐coordinated salicylidene‐based copolymers. The linear copolymers were prepared by polycondensation of the metal‐coordinated salicylidene monomer with acyl or aryl dichloride. Structure analysis was carried out by ¹H and ¹³C NMR, FTIR, and elemental analysis. Physicochemical evaluation was carried out using DSC and thermogravimetry. The surface properties were analyzed by contact angle measurements and the crystallinity was determined by polarizing microscopy and AFM. Finally, polymer electrical conductivity and biocompatibility were examined. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 2568–2577, 2006     

Photo‐cross‐linked biodegradable thermo‐ and pH‐responsive hydrogels for controlled drug release

A new strategy was developed to prepare thermo‐ and pH‐sensitive hydrogels by the crosslinking of poly(N‐isopropylacrylamide) with a biodegradable crosslinker derived from poly(L ‐glutamic acid). Hydrogels were fabricated by exposing aqueous solutions of precursor containing photoinitiator to UV light irradiation. The swelling behaviors of hydrogels at different temperatures, pHs, and ionic strengths were examined. The hydrogels shrank under acidic condition or at temperature above their collapse temperature and would swell in neutral or basic media or at lower temperature. These processes were reversible as the pH or temperature changed. All hydrogels exhibited no weight loss in the simulated gastric fluid but degraded rapidly in the simulated intestinal condition. Bovine serum albumin were used as a model protein drug and loaded into the hydrogels. The in vitro drug release experiment was carried out at different pH values and temperatures. The pH and temperature dependent release behaviors indicated the promising application of these materials as stimuli‐responsive drug delivery vehicles. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Novel biodegradable superabsorbent hydrogels derived from cotton cellulose and succinic anhydride: Synthesis and characterization

The synthesis of novel superabsorbent hydrogels was investigated with the reaction of cotton cellulose and succinic anhydride (SA) in the presence of 4‐dimethylaminopyridine as an esterification catalyst in a mixture of lithium chloride (LiCl) and N‐methyl‐2‐pyrrolidinone (NMP) or in a mixture of tetrabutylammonium fluoride (TBAF) and dimethyl sulfoxide (DMSO), followed by NaOH neutralization. Interestingly, a hydrogel was obtained without any crosslinking agent, and this indicated the partial formation of a diester between the cellulosic hydroxyl group and SA. The products obtained in LiCl/NMP exhibited superior absorbency to these obtained in TBAF/DMSO. The former absorbed an amount of water about 400 times its dry weight, and this was comparable to a conventional sodium polyacrylate superabsorbent hydrogel. Furthermore, in an aqueous NaCl solution, the absorbency of the product hydrogels was higher than that of the sodium polyacrylate superabsorbent hydrogel. The formed hydrogels biologically degraded almost completely after 25 days, and this showed their excellent biodegradability. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 99: 3251–3256, 2006     

Synthesis and characterization of biodegradable lactic acid‐based polymers by chain extension

BACKGROUND: Poly(lactic acid) (PLA), coming from renewable resources, can be used to solve environmental problems. However, PLA has to have a relatively high molecular weight in order to have acceptable mechanical properties as required in many applications. Chain‐extension reaction is an effective method to raise the molecular weight of PLA. RESULTS: A high molecular weight biodegradable lactic acid polymer was successfully synthesized in two steps. First, the lactic acid monomer was oligomerized to low molecular weight hydroxyl‐terminated prepolymer; the molecular weight was then increased by chain extension using 1,6‐hexamethylene diisocyanate as the chain extender. The polymer was characterized using ¹H NMR analysis, gel permeation chromatography, differential scanning calorimetry and Fourier transform infrared spectroscopy. The results showed that the obtained polymer had a M_n of 27 500 g mol^?1 and a M_w of 116 900 g mol^?1 after 40 min of chain extension at 180 °C. The glass transition temperature (T_g) of the low molecular weight prepolymer was 47.8 °C. After chain extension, T_g increased to 53.2 °C. The mechanical and rheological properties of the obtained polymer were also investigated. CONCLUSION: The results suggest that high molecular weight PLA can be achieved by chain extension to meet conventional uses. Copyright © 2008 Society of Chemical Industry     

Synthesis and characterization of novel polyglycerol hydrogels containing L‐lactic acid groups as pendant acidic substituents: pH‐Responsive polyglycerol‐based hydrogels

Novel pH‐responsive polyglycerol (PG)‐based hydrogels were successfully synthesized through the reaction of epichlorohydrin with L ‐lactic acid (LLA) in the presence of sodium hydroxide (NaOH), and cetyltrimethylammonium bromide as a phase transfer catalyst at room temperature, followed by hydrolysis, polymerization, and crosslinking reactions. The resultant gel was characterized by carbon nuclear magnetic resonance spectroscopy, X‐ray photoelectron spectroscopy, and Fourier transform infrared measurement, and it was found that incorporated LLA was bound to PG network as a pendant acidic substituent by the hydroxyl group of LLA (PGL gel). The PGL hydrogels with different LLA contents and equilibrium swelling ratios (ESRs) were prepared by changing the feed ratios of materials. The results determined by chemical titration showed that under the applied conditions the efficiency of introducing the carboxyl group into PG network was about 86% and the amount of LLA in the hydrogel reached to about 17 wt %. The swelling behavior of the hydrogels in different environmental mediums was investigated, and the results showed that the hydrogels are pH‐, ionic strength‐, and cationic charge‐responsive. The hydrogels also have the reversible swelling/deswelling properties. These pH‐responsive PG‐based hydrogels will have potential applications in biomedical and related areas. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation and characterization of polyacrylic acid‐poly(vinyl alcohol)‐based interpenetrating hydrogels

Some structural features of hydrogels from poly(acrylic acid) (PAAc) of various crosslinking degrees have been investigated through mechanical and swelling measurements. Interpenetrating polymer hydrogels (IPHs) of poly(vinyl alcohol) (PVA) and PAAc have been prepared by a sequential method: crosslinked PAAc chains were formed in aqueous solution by crosslinking copolymerization of acrylic acid and N,N‐methylenebisacrylamide in the presence of PVA. The application of freeze–thaw (F–T) cycles leads to the formation of a PVA hydrogel within the synthesized PAAc hydrogel. The swelling and viscoelastic properties of the IPHs were evaluated as a function of the content of crosslinker and the application of one F–T cycle. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 5789–5794, 2006     

Synthesis and characterization of hydrogels containing biodegradable polymers

BACKGROUND: Amphiphilic block and graft copolymers constitute a very interesting class of polymers with potential for biomedical applications, due to their special characteristics, which derive from the combination of properties of hydrophilic and hydrophobic moieties. In this work, the synthesis and biodegradation of poly(2‐hydroxyethyl methacrylate)‐graft‐poly(L ‐lactide) are studied. RESULTS: The graft copolymers were synthesized using the macromonomer technique. In a first step, methacryloyl‐terminated poly(L ‐lactide) macromonomers were synthesized in a wide molecular weight range using different catalysts. Subsequently, these macromonomers were copolymerized with 2‐hydroxyethyl methacrylate in order to obtain a graft copolymer. These new materials resemble hydrogel scaffolds with a biodegradable component. The biodegradation was studied in hydrolytic and enzymatic environments. The influence of different parameters (molecular weight, crystallinity, ratio between hydrophilic and hydrophobic components) on the degradation rate was investigated. CONCLUSION: Based on this study it will be possible to tailor the release properties of biodegradable materials. In addition, the materials will show good biocompatibility due to the hydrophilic poly(2‐hydroxyethyl methacrylate) hydrogel scaffold. This kind of material has potential for many applications, like controlled drug‐delivery systems or biodegradable implants. Copyright © 2008 Society of Chemical Industry     

Synthesis and characterization of amphiphilic biodegradable poly(glutamic acid‐co‐lactic acid‐co‐glycolic acid) by direct polycondensation

Poly(glutamic acid‐co‐lactic acid‐co‐glycolic acid) (PGLG), an amphiphilic biodegradable copolymer, was synthesized by simply heating a mixture of L ‐glutamic acid (Glu), DL ‐lactic acid, and glycolic acid with the present of stannous chloride. The unique branched architecture comprising of glutarimide unit, polyester unit, and polyamide unit was confirmed by NMR spectrum. The PGLG was soluble in many organic solvents and aqueous solution of sodium hydroxide (pH ≥ 9.0). The thermal properties were evaluated using thermogravimetric analysis and differential scanning calorimetry. Molecular weights were determined by ¹H NMR end‐group analysis and GPC, respectively, and the results indicated that the higher Glu content resulted in a decrease of the molecular weight. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Synthesis and characterization of biodegradable poly(butylene succinate‐co‐propylene succinate)s

Biodegradable polyesters such as poly(butylene succinate) (PBS), poly(propylene succinate) (PPS), and poly(butylene succinate‐co‐propylene succinate)s (PBSPSs) were synthesized respectively, from 1,4‐succinic acid with 1,4‐butanediol and 1,3‐propanediol through a two‐step process of esterification and polycondensation in this article. The composition and physical properties of both homopolyesters and copolyesters were investigated via ¹H NMR, DSC, TGA, POM, AFM, and WAXD. The copolymer composition was in good agreement with that expected from the feed composition of the reactants. The melting temperature (T_m), crystallization temperature (T_c), crystallinity (X), and thermal decomposition temperature (T_d) of these polyesters decreased gradually as the content of propylene succinate unit increased. PBSPS copolyesters showed the same crystal structure as the PBS homopolyester. Besides the normal extinction crosses under the polarizing optical microscope, the double‐banded extinction patterns with periodic distance along the radial direction were also observed in the spherulites of PBS and PBSPS. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Synthesis,characterization, and in vitro cytotoxicity of chitosan hydrogels containing nanogold

Hydrogels due to their unique properties are characterized by a wide range of applications. In presented research a series of hydrogel based on chitosan and modified with nanogold have been prepared by photopolymerization. Based on the research it can be concluded that presented hydrogels are interesting materials that can play a key role in medicine. They are characterized by biocompatibility to simulated physiological fluids and do not show any cytotoxicity to the dermal cells. Furthermore, they are characterized by relatively high sorption capacity. These results show the possibility of the potential use of these hydrogels for biomedical purposes.     

Synthesis and characterization of multi‐block copolymers containing poly [(3‐hydroxybutyrate)‐co‐(3‐hydroxyvalerate)] and poly(ethylene glycol)

Various problems, including high crystallinity, high melting temperature, poor thermal stability, hydrophobicity and brittleness, have impeded many practical applications of poly[(3‐hydroxybutyrate)‐co‐(3‐hydroxyvalerate)] (PHBV) as an environmentally friendly material and biomedical material. In the work reported here, multi‐block copolymers containing PHBV and poly(ethylene glycol) (PHBV‐b‐PEG) were synthesized with telechelic hydroxylated PHBV as a hard and hydrophobic segment, PEG as a soft and hydrophilic segment and 1,6‐hexamethylene diisocyanate as a coupling reagent to solve the problems mentioned above. PHBV and PEG blocks in PHBV‐b‐PEG formed separate crystalline phases with lower crystallinity levels and lower melting temperatures than those of phases formed in the precursors. The crystallite dimensions of the two blocks in PHBV‐b‐PEG were smaller than those of the corresponding precursors. Compared to values for the original PHBV, the maximum decomposition temperature of the PHBV block in PHBV‐b‐PEG was 16.0 °C higher and the water contact angle was 9° lower. In addition, the elongation at break was 2.8% for a pure PHBV fiber but 20.9% for a PHBV/PHBV‐b‐PEG fiber with a PHBV‐b‐PEG content of 30%. PHBV‐b‐PEGs can overcome some of the disadvantages of pure PHBV; it is possible that PHBV might be a good candidate for the formulation of environmentally friendly materials and biomedical materials. Copyright © 2010 Society of Chemical Industry     

Swelling–deswelling behavior of poly(acrylamide‐co‐maleic acid) hydrogels

In this study the poly(acrylamide‐co‐maleic acid) hydrogels containing small amounts of maleic acid have been synthesized, and the effect of pH, ionic strength, and nature of counterions on the equilibrium water uptake has been investigated. The incorporation of small amount of maleic acid results in the transition of swelling mechanism from Fickian to non‐Fickian. The equilibrium mass swelling has been found to increase with pH of the swelling medium while increase in ionic strength causes a decrease in the swelling. The amount of maleic acid present in the hydrogel affects the swelling behavior in rather an unusual way. With lower acid contents, the equilibrium mass swelling increases while higher concentrations of maleic acid cause a decrease in the degree of swelling. The hydrogels have been found to undergo a number of swelling–deswelling cycles when pH of the swelling medium changes from 8.0 to 2.0. Hydrogels require more time to deswell compared to the time required for swelling, which has been explained on the basis of the fact that gels follow different mechanisms for the two processes. Various swelling parameters such as equilibrium mass swelling, diffusion coefficient, intrinsic diffusion coefficient, swelling exponent, etc., have been evaluated. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 2782–2789, 2001     

Synthesis and characterization of new biodegradable fluorescing poly(amide‐anhydrides)

Biodegradable/alternate/poly(amide‐anhydrides), [? C(O)PhNHC(O)(CH₂) _nC(O)O? ] _x, were synthesized by melt polycondensation, where n was 2, 3 or 4. The polymers have been characterized by NMR, DSC, wide‐angle X‐ray diffractometry and fluorometry. All the polymers are amorphous and their T_g ranges from 60 to 80 °C. Poly(p‐(carboxyethylformamido)benzoic anhydride) (PCEFB) as a film or in solution in chloroform can emit strong fluorescence, which was not observed for the other two polyanhydrides (n = 3, 4). The maximum emission wavelength varies with the excitation wavelength, 480 and 520 nm at the excitation wavelength of 470 nm, and 430 nm at 356 nm. In addition, the fluorescence intensities increase linearly with the molecular weight of PCEFB. Such inherent fluorescing properties of PCEFB, together with its biodegradability, make the polymer a potential visible matrix for drug delivery. © 2001 Society of Chemical Industry     

Effect of crosslinking concentration on mechanical and thermodynamic properties in acrylic acid–co–methyl methacrylate hydrogels

The mechanical and thermodynamic properties of poly(acrylic acid‐co‐methyl methacrylate) hydrogels with varying crosslinker N,N′‐methylenebisacrylamide (NMBA) content are reported. A higher NMBA content generally led to a stronger and harder gel with lower water content. Swelling capacity decreased as the NMBA concentration increased between 0.5% and 2%, remaining constant beyond this range. The temperature changes of the partial molar Gibbs free energy of dilution and enthalpic and entropic contributions were examined. The thermodynamic parameters showed that swelling was an unfavorable and endothermic process. The freezing and nonfreezing water in the hydrogel was determined by differential scanning calorimetry (DSC). Freezing water content decreased with increasing crosslinker (NMBA) content, whereas the ratio of nonfreezing water to total water content increased with NMBA content because of the promoting of hydrophobic interactions in the hydrogels. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 4016–4022, 2006     

Preparation and swelling behavior of biodegradable hydrogels based on α,β‐poly(N‐2‐hydroxyethyl‐DL‐aspartamide)

Biodegradable polymers and the hydrogels have been increasingly applied in a variety of biomedical fields and pharmaceutics. α,β‐Poly(N‐2‐hydroxyethyl‐DL ‐aspartamide), PHEA, one of poly(amino acid)s with hydroxyethyl pendants, are known to be biodegradable and biocompatible, and has been studied as an useful biomaterial, especially for drug delivery, via appropriate structural modification. In this work, hydrogels based on PHEA were prepared by two‐step reaction, that is, the crosslinking of polysuccinimide, the precursor polymer, with oligomeric PEG or PEI‐diamines and the following nucleophilic ring‐opening reaction by ethanolamine. Soft hydrogels possessing varying degrees of gel strength could be prepared easily, depending on the amount of different crosslinking reagents. The swelling degrees, which were in the range of 10–40 g–water/dry gel, increased somewhat at higher temperature, and also at alkaline pH of aqueous solution. A typical hydrogel remained almost unchanged for 1 week, at 37°C in phosphate buffer of pH 7.4, and then seemed to degrade slowly as time. A porous scaffold could be fabricated by the freeze drying of water‐swollen gel. The PHEA‐based hydrogels have potential for useful biomaterial applications including current drug delivery system. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3741–3746, 2003     

Improvement in the water‐absorbing properties of superabsorbent polymers (acrylic acid‐co‐acrylamide) in supercritical CO2

Superabsorbent resins prepared by ultraviolet radiation‐inducing polymerization techniques with acrylic acid/acrylamide were treated with supercritical carbon dioxide (SC‐CO₂). The water‐absorbing properties of the treated resins were greatly improved. The water‐absorbing properties of resins treated with SC‐CO₂ in the pressure range of 10–35 MPa and the temperature range of 40–60°C were studied. The effects of the treatment time and depressurizing speed of CO₂ after treatment were also examined. Obviously, different results were found for particles of different sizes. Smaller particles were more efficient under the same treatment conditions. Samples were tested with differential scanning calorimetry. The results showed that the plasticizing effect of CO₂ reduced the glass‐transition temperature of the polymer, and it was proposed that the plasticization effect might have led to polymer chain redistribution and better flexibility. Minor changes in the surface morphology of the particles were observed with scanning electron microscopy. The extraction of the unpolymerized monomers by SC‐CO₂ was also studied. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2272–2278, 2002     

Synthesis and evaluation of sucrose‐containing polymeric hydrogels for oral drug delivery

Biodegradable and biocompatible copolymeric hydrogels based on sucrose acrylate, N‐vinyl‐2‐pyrrolidinone, and acrylic acid were designed and synthesized. Because of the growing importance of sugar‐based hydrogels as drug delivery systems, these new pH‐responsive sucrose‐containing copolymeric hydrogels were investigated for oral drug delivery. The sucrose acrylate monomer was synthesized and characterized. The copolymeric hydrogel was synthesized by free‐radical polymerization. Azobisisobutyronitrile (AIBN) was the free‐radical initiator employed and bismethyleneacrylamide (BIS) was the crosslinking agent used for hydrogel preparations. Homopolymeric vinyl pyrrolidone hydrogels were also prepared by the same technique. The hydrogels were characterized by differential scanning calorimetry, thermogravimetric analysis, and scanning electron microscopy. Equilibrium swelling studies were carried out in enzyme‐free simulated gastric and intestinal fluids (SGF and SIF, respectively). These results indicate the pH‐responsive nature of the hydrogels. The gels swelled more in SIF than in SGF. A model drug, propranolol hydrochloride (PPH), was entrapped in these gels and the in vitro release profiles were established separately in both enzyme‐free SGF and enzyme‐free SIF. The drug release was found to be faster in SIF. About 93 and 99% of the entrapped drug was released over a period of 24 h in SGF and SIF, respectively. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 2597–2604, 2002     

Synthesis of amphiphilic pseudopolyamino acid‐containing ABC‐triblock copolymers and micellar characterizations

This study describes the synthesis of amphiphilic ABC‐triblock copolymers comprising a central pseudopoly(4‐hydroxy‐L ‐proline) segment and terminal hydrophilic poly(ethylene glycol)methyl ether as well as hydrophobic poly(ε‐caprolactone) blocks. Differential scanning calorimetry, ¹H‐NMR spectroscopy, and gel permeation chromatography are used to characterize the copolymers. The thermal properties (T_g and T_ms) of the triblock copolymers depend on the composition of polymers. Larger amounts of ε‐CL incorporated into the macromolecular backbone increased T_g and T_ms. Fluorescence spectroscopy, transmission electron microscopy, and dynamic light scattering are utilized to investigate their micellar characteristics in the aqueous phase. Observations showed a higher critical micelle concentration with higher hydrophilic components in the copolymers. The micelle exhibited a core‐shell‐corona and/or vesicle shape, and the average size was less than 300 nm. Drug entrapment efficiency and drug loading of micelles depending on the composition of block polymers are also described. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010