Synthesis and characterization of poly{N‐[3‐(dimethylamino) propyl] methacrylamide‐co‐itaconic acid} hydrogels for drug delivery

A novel pH‐sensitive hydrogel system composed of itaconic acid (IA) and N‐[3‐(dimethylamino) propyl] methacrylamide was designed. This system was prepared by aqueous copolymerization with N,N‐methylene bisacrylamide as a chemical crosslinker. The chemical structure of the hydrogels was characterized by Fourier transform infrared (FTIR) spectroscopy. The microstructure and morphology of the hydrogels were evaluated by X‐ray diffraction (XRD) and scanning electron microscopy (SEM). The SEM study of hydrogels on higher magnification revealed a highly porous morphology with uniformly arranged pores ranging from 40 to 200 μm in size. XRD analysis revealed the amorphous nature of the hydrogels, and it was found that an increase in the IA content in the monomer feed greatly reduced the crystallinity of the hydrogels. Swelling experiments were carried out in buffer solutions at different pH values (1.2–10) at 37°C ± 1°C to investigate their pH‐dependent swelling behavior and dimensional stability. An increase in the acid part (IA) increased the swelling ratio of the hydrogels. Temperature‐sensitive swelling of the hydrogels was investigated at 20–70°C in simulated intestinal fluid. The hydrogels swelled at higher temperatures and shrank at lower temperatures. 5‐Aminosalicylic acid (5‐ASA) was selected as a model drug, and release experiments were carried out under simulated intestinal and gastric conditions. 5‐ASA release from the poly N‐[3‐(dimethylamino) propyl] methacrylamide‐co‐itaconic acid‐80 (PDMAPMAIA‐80) hydrogel was found to follow non‐Fickian diffusion mechanism under gastric conditions, and a super case II transport mechanism was found under intestinal conditions. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Preparation and application in drug controlled delivery of pH‐sensitive P(CE‐co‐DMAEMA‐co‐MEG) hydrogel

A pH‐sensitive hydrogel [P(CE‐co‐DMAEMA‐co‐MEG)] was synthesized by the free‐radical crosslinking polymerization of N,N‐dimethylaminoethyl methacrylate (DMAEMA), poly(ethylene glycol) methyl ether methacrylate(MPEG‐Mac) and methoxyl poly(ethylene glycol)‐poly(caprolactone)‐methacryloyl methchloride (PCE‐Mac). The effects of pH and monomer content on swelling property, swelling and deswelling kinetics of the hydrogels were examined and hydrogel microstructures were investigated by SEM. Sodium salicylate was chosen as a model drug and the controlled‐release properties of hydrogels were pilot studied. The results indicated that the swelling ratios of the gels in stimulated gastric fluids (SGF, pH = 1.4) were higher than those in stimulated intestinal fluids (SIF, pH = 7.4), and followed a non‐Fickian and a Fickian diffusion mechanism, respectively. In vitro release studies showed that its release rate depends on different swelling of the network as a function of the environmental pH and DMAEMA content. SEM micrographs showed homogenous pore structure of the hydrogel with open pores at pH 1.4. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40737.     

Synthesis,Characterization, and drug release study of acrylamide‐co‐itaconic acid based smart hydrogel

A new kind of pH and temperature responsive poly(acrylamide‐co‐itaconic acid) hydrogel was prepared by free radical polymerization using ammonium persulfate as initiator and different comonomer ratios. The hydrogels were characterized in terms of chemical composition, swelling‐deswelling behavior, morphology, crystallographic behavior, and drug release properties. All the hydrogels showed high swelling ability in aqueous solutions, the maximum being at pH 7. Swelling decreased on either side of pH 7 (i.e., both in acidic and alkaline region) and increased with increase in temperature. The hydrogel with 10 mol% itaconic acid (IA) absorbed maximum water among the copolymer gels. The cellular structures of the hydrogels were clearly revealed by microscopic analysis and SEM pictures. Swelling of the gels in water followed non‐Fickian type of diffusion principle. The hydrogel was proved to be a controlled release vehicle, for example in drug delivery by using its smart properties. The hydrogel with 10 mol% IA also absorbed maximum amount of drug (ascorbic acid) under study. Incorporation of drug in hydrogel matrix was established from XRD peak analysis. POLYM. ENG. SCI., 55:113–122, 2015. © 2014 Society of Plastics Engineers     

Control release of some pesticides from starch/(ethylene glycol‐co‐methacrylic acid) copolymers prepared by γ‐irradiation

Starch/(Ethylene glycol‐co‐Methacrylic acid) [Starch/(EG‐co‐MAA)] hydrogels were designed for controlled delivery of pesticides, such as Fluometuron (FH); Thiophanate Methyl (TF) and Trifluralin (TI) which are use in the agricultural field. The delivery device was prepared by using γ‐irradiation and was characterized by FTIR, DSC, and SEM. The swelling behavior of hydrogels as a function of copolymer composition and irradiation dose was detected. This article discusses the swelling kinetics of polymer matrix and release dynamics of Trifluralin from hydrogels for the evaluation of the diffusion mechanism and diffusion coefficients. The values of the diffusion exponent ‘n’ for both the swelling of hydrogels and the release of Trifluralin from the hydrogels have been observed between 0.56 and 0.86 when the MAA content in the polymers was varied from 20 to 80 wt %, respectively. It is inferred from the values of the ‘n’ that non‐Fickian diffusion mechanism has occurred for different EG/MAA compositions. The release rate from matrices prepared under different conditions was studied to determine which factors have the most affect and control over the hydrogel matrix release property. The preparation conditions such as EG/MAA hydrogel composition, pesticide concentration, type of pesticide and irradiation dose greatly affect the pesticide release rate, which also influenced by the pH and temperature of the matrix‐surrounding medium. The pesticide release rate decreased as the irradiation dose and pH increased, but it increased as the MAA content, pesticide concentration and temperature increased. The release rate of Trifluralin is the highest one, whereas the Fluometuron is the lowest. The properties of the prepared hydrogels may make them acceptable for practical use as bioactive controlled release matrices. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Gelatin based pH‐sensitive hydrogels for colon‐specific oral drug delivery: Synthesis,characterization, and in vitro release study

Based on gelatin (Gltn) and acrylic acid (AAc), biodegradable pH‐sensitive hydrogel was prepared using gamma radiation as super clean source for polymerization and crosslinking. Incorporation of PAAc in the prepared hydrogel was confirmed by Fourier transform infrared spectroscopy (FTIR). The effect of PAAc content on the morphological structure of the prepared hydrogel swollen at pH 1, 5, and 7 was examined using scanning electron microscopy (SEM). The results showed the dependence of the porous structure of the prepared hydrogels on AAc content and the pH of the swelling medium. Swelling properties of gelatin/acrylic acid copolymer hydrogels with different AAc contents were investigated at different pH values. Swelling data showed that the prepared hydrogels possessed pronounced pH sensitivity. In vitro release studies were performed to evaluate the hydrogel potential as drug carrier using ketoprofen as a model drug. Experimental data showed that the release profile depends on both hydrogel composition and pH of the releasing medium. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Synthesis of smart hydrogels by radiation polymerisation for use as slow drug delivery devices

This article deals with the modification of medicinally important psyllium polysaccharide with acrylamide through radiation crosslinked polymerisation for the design of double potential hydrogels meant for slow release of insulin. Here the double potential is due to the inherent blood sugar lowering ability of psyllium and release of insulin in controlled manner from the drug loaded hydrogels. Synthesis of hydrogels and their characterisation by scanning electron micrography (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and swelling studies have been discussed. The release dynamics of model drug insulin from the hydrogels has been studied for the evaluation of the release mechanism. The release of the drug from the hydrogels occurred through non‐Fickian diffusion mechanism.     

On physical and antibacterial properties and drug release behavior of poly(vinyl alcohol) hydrogels: effect of drug loaded chitosan nanoparticles

This paper deals with influence of chitosan nanoparticles (CNPs) loaded by tetracycline, as a drug, on the physico-mechanical and antibacterial properties as well as drug release behavior of poly(vinyl alcohol), PVA, hydrogels prepared by electron beam irradiation. The formation of spherical chitosan particles in nanoscale size prepared by an ionic gelation method was confirmed by FTIR and UV spectroscopy, and scanning electron microscopy analyses. The drug release kinetic studies from drug loaded chitosan nanoparticles (DLCNPs) at pH = 7.4 revealed a linear and steady release behavior over long period of time. The theoretical analysis of the swelling kinetic data, using Peppas’s model showed that the swelling kinetic is governed by Fickian diffusion for all the prepared hydrogels, however, the water diffusion coefficient, and therefore, the swelling content were lower for the hydrogels loaded with DLCNPs as compared to the ones with the neat drug. In agreement with these results, the hydrogels containing DLCNPs exhibited a more controlled drug release behavior with significantly stronger antibacterial activity. The tensile mechanical properties of the hydrogels not affected by the DLCNPs were found to be suitable for wound dressing applications.     

A pH-, thermo-, and glucose-, triple-responsive hydrogels: Synthesis and controlled drug delivery

In this work, a series of hydrogels were prepared by copolymerization of (2-dimethylamino) ethyl methacrylate (DMAEMA) and 3-acrylamidephenylboronic acid (AAPBA). The structure of the resultant hydrogels was studied by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The experimental results from swelling studies revealed that the hydrogels displayed definite glucose sensitivity under physiological conditions, as well as sharp changes in the mesh size of their network as a function of the pH and temperature of the swelling media. Bovine serum albumin (BSA) was selected as a model compound when examining protein release from hydrogels. The results suggested that the temperature, pH and glucose concentration of buffer solutions greatly influenced release profiles.     

A fast pH-responsive IPN hydrogel: Synthesis and controlled drug delivery

A series of fast pH-responsive silk sericin (SS)/poly(methacrylic acid) (PMAA) IPN hydrogels were prepared by the simultaneous-IPN method. The structure of the resultant IPN hydrogels was characterized by fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The swelling experimental of the IPNs revealed that the hydrogels displayed definite pH sensitivity under physiological conditions, as well as sharp changes in the mesh size of their network as a function of the composition and pH of the swelling media. Bovine serum albumin (BSA) was chosen as a model protein to evaluate the permeation profile through the IPNs in both the simulated gastric and intestinal pH conditions. In all cases, it was found that the release rate of BSA was lower in acidic media (pH 2.6) and higher in basic media (pH 7.4).     

Design of dietary polysaccharide and binary monomer mixture of acrylamide and 2-acrylamido-2-methylpropane sulphonic acid based antiviral drug delivery devices

The present article discusses the functionalization of psyllium by binary monomer mixture of acrylamide and 2-acrylamido-2-methylpropane sulphonic acid to develop the new drug delivery devices. These were characterized by SEMs, FTIR, TGA and swelling studies. The swelling kinetics of the hydrogels and release dynamics of drug (indinavir sulphate) from the drug loaded hydrogels has been studied for the evaluation of the swelling and drug release mechanism respectively. The release of the drug from the hydrogels occurred through Fickian diffusion mechanism in pH 2.2 buffer. The antiviral activity of indinavir sulphate for AIDS, anti-diarrhoeal action of psyllium and inhibitory effects of sulphated polymers on STD pathogens will enhance the potential of the drug delivery devices.     

Chitosan‐based interpolymeric pH‐responsive hydrogels for in vitro drug release

Two series of pH‐responsive biodegradable interpolymeric (IPN) hydrogels based on chitosan (Ch) and poly(vinyl alcohol) (PVA) were prepared for controlled drug release investigations. The first series was chemically crosslinked with different concentrations of glutaraldehyde and the second was crosslinked upon γ‐irradiation by different doses. The equilibrium swelling characteristics were investigated for the gels at 37°C in buffer solutions of pH 2.1 and 7.4 as simulated gastric and intestinal fluids, respectively. 5‐Fluorouracil (FU) was entrapped in the hydrogels, as a model therapeutic agent, and the in vitro release profiles of the drug were established at 37°C in pH 2.1 and 7.4. FTIR, SEM, and X‐ray diffraction analyses were used to characterize and investigate the structural changes of the gels with the variation of the blend composition and crosslinker content before and after the drug loading. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2864–2874, 2007     

Synthesis and characterization of chitosan/cloisite 30B film for controlled release of ofloxacin

In this research program, chitosan film was prepared by blending chitosan with Cloisite 30 B at different concentrations 0 wt %, 1 wt %, and 2.5 wt %. The blends were characterized by Fourier transmission infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X‐ray diffraction (XRD) analysis. From the FTIR spectra the various groups present in chitosan/C 30 B blend were monitored. The homogeneity, morphology, and crystallinity of the blends were ascertained from SEM and XRD data, respectively. The most suitable form of blend was taken and used as a carrier for the controlled release of ofloxacin. The swelling studies have been carried out at different drug loading. Drug release kinetics was analyzed by plotting the cumulative release data versus time by fitting to an exponential equation which indicated the occurrence of non‐Fickian type of kinetics. The drug release was investigated at different pH medium and it was found that the drug release depends upon the pH medium as well as the nature of matrix. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Equilibrium adsorption isotherm and controlled release of antibiotic drug chloroamphenicol from poly(2‐vinyl pyridine/acrylic acid) hydrogels prepared by gamma radiation

High water sorption of 2‐vinyl pyridine (2‐VP)/acrylic acid (AAc) hydrogel were prepared by free‐radical polymerization in aqueous solution of 2‐VP with AAc as comonomer. The amount of ionic monomer (AAc), the irradiation dose of prepared hydrogel, the pH, and the concentration of drug play an important factor on loading, adsorption, and releasing of water‐soluble chloroamphenicol drug. As a result of dynamic swilling tests, the effect of relative content of AAc on the swelling showed that it allowed a non‐Fickian type of water diffusion. The adsorption of the drug onto (2‐VP/AAc) hydrogels was studied by Freundlish adsorption isotherm. The drug concentrations showed an influence on the adsorption of drug which increased with increasing AAc content. From Freundlish adsorption isotherm, the empirical constants, k and n, can be evaluated and showed the ability of hydrogel to be loaded by the drug and the affinity of the drug to be uptake onto the hydrogel respectively. FTIR, TGA, and SEM techniques were used to study the characterization of hydrogel (2‐VP/AAc). Additionally, the release of the drug loaded from hydrogel discs was studied microbiologically to show that hydrophilic structure of the hydrogel has an antimicrobial effect as a dehydration of cytoplasm and unbalance of the cell wall functions. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Release of vitamin B12 from poly(N‐vinyl‐2‐pyrrolidone)‐crosslinked polyacrylamide hydrogels: A kinetic study

Hydrogels, composed of poly(N‐vinyl‐2‐pyrrolidone) and crosslinked polyacrylamide, were synthesized and the release of vitamin B₁₂ from these hydrogels was studied as a function of the degree of crosslinking and pH of the external swelling media. The three drug‐loaded hydrogel samples synthesized with different crosslinking ratios of 0.3, 0.7, and 1.2 (in mol %) follow different drug‐release mechanisms, that is, chain relaxation with zero‐order, non‐Fickian and Fickian, or diffusion‐controlled mechanisms. To establish a correlation between their swelling behavior and drug‐release mechanism, the former was studied by the weight‐gain method and, at the same time, the concentration of the drug released was studied colorimetrically. Various swelling parameters such as the swelling exponent n, gel‐characteristic constant k, penetration velocity v, and diffusion coefficient D were evaluated to reflect the quantitative aspect of the swelling behavior of these hydrogels. Finally, the drug‐release behavior of the hydrogels was explained by proposing the swelling‐dependent mechanism. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 1706–1714, 2000     

Swelling dynamics of IPN hydrogels including acrylamide‐acrylic acid‐chitosan and evaluation of their potential for controlled release of piperacillin‐tazobactam

For to be used in controlled releasing of piperacillin‐tazobactam, a series of semi and full IPN type hydrogels composed of acrylic acid (AA), acrylamide (AAm) and Chitosan (CS) were prepared via free‐radical polymerization. Ethylene glycol dimethacrylate (EGDMA) was used for crosslinking of PAAm and PAA chains to form semi‐IPN hydrogels. However, the full‐IPN type hydrogels were prepared by using glutaraldehyde (GA) and EGDMA as cocrosslinkers. Characteristics of the hydrogels were investigated by swelling experiments and SEM and FTIR analysis. Generally, full‐IPN type hydrogels swell much more than the semi‐IPN types. By comparing the full‐IPN type hydrogels in between, it is found that the increasing amount of GA causes the decreasing in S% values from 4860 to 4300%. Releasing of piperacillin‐tazobactam from selected three hydrogels were investigated in phosphate buffer solution at pH = 7.4, 37°C. The kinetic release parameters, n and k were calculated and non‐Fickian type diffusion was established for these hydrogels. The behaviors of the piperacillin‐tazobactam loaded hydrogels in Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) culture suspensions were also studied and the statistically significant differences for the microorganism growth values were determined. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Preparation and characterization of pH‐ and temperature‐responsive semi–interpenetrating polymer network hydrogels based on linear sodium alginate and crosslinked poly(N‐isopropylacrylamide)

In this study, pH‐ and temperature‐responsive hydrogels based on linear sodium alginate (SA) and crosslinked poly(N‐isopropylacrylamide) (PNIPAAm) were prepared by semi‐interpenetrating network (semi‐IPN) technique. The dually responsive hydrogels were characterized by FTIR, DSC, and SEM, and their temperature‐ and pH‐responsive behaviors were investigated by measuring equilibrium swelling ratios and pulsatile swelling experiments. The results showed that these hydrogels underwent volume phase transition at around 33°C irrespective of the pH value of the medium, but their pH sensitivity was evident only below their volume phase transition temperature. Under basic conditions, the swelling ratios of SA/PNIPAAm semi‐IPN hydrogels were greater than that of pure PNIPAAm hydrogel and increased with increasing SA content incorporated into the hydrogels, but the case was inverse under acidic conditions. The pulsatile swelling experiments indicated that the higher the SA content in SA/PNIPAAm semi‐IPN hydrogels, the faster the response rate to both pH and temperature change. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 1931–1940, 2005     

Kinetic degradation and controlled drug delivery system studies for sensitive hydrogels prepared by gamma irradiation

Ternary mixtures of N‐vinyl‐2‐pyrrolidone/itaconic acid and gelatin were irradiated by gamma rays at 30 kGy/s and at ambient temperature to prepared poly (NVP/IA and G) hydrogels. Poly (NVP/IA) hydrogels were prepared in different compositions (NVP/IA) mole ratio, (100/0), (98/1.5), (96.5/3.5), and (93/7.0) at 30 kGy. Then adding gelatin at different content (5, 10, 15, 20) mg to the best composition (NVP/IA/H₂O) (93/7)% for the characterization of network structure of these hydrogels, kinetic swelling drug release behavior and Scan Electron Microscope was studied. The equilibrium degree of swelling for P(NVP/IA) and P(NVP/IA/G) copolymer and the swelling‐degradation kinetics were also studies. According to dynamic swelling studies, both the diffusion exponent and the diffusion coefficient increase with increasing content of (IA), whereas, the addition of gelatin to (NVP/IA) composition by different content did not lead to any significant change in swelling percent. Also, the swelling behavior of copolymer hydrogels in response to pH value of the external media was studied, it is noted that the highest swelling values were at pH 4. The in vitro drug release behavior of these hydrogels was examined by quantification analysis with a UV/VIS spectrophotometers. Chlorpromazine hydrochloride was loaded into dried hydrogels to investigate the stimuli‐sensitive property at the specific pH and the drug release profile of these pH‐sensitive hydrogels in vitro. The release studies show that the highest value of release was at pH 4 which can be used for drug delivery system. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

In vitro degradation and protein release of semi‐IPN hydrogels consisted of poly(acrylic acid‐acrylamide‐methacrylate) and amylose

The enzymatic degradation mechanism of semi‐interpenetrating network (semi‐IPN) hydrogel of poly (acrylic acid‐acrylamide‐methacrylate) crosslinked by azocompound and amylose in vitro was investigated in the presence of Fungamyl 800L (α‐amylase) and rat cecum content (cecum bacteria). The degradation mechanism involves degradable competition, i.e., reduction of azo crosslinkage is dominant in the earlier period of degradation. Subsequently, the degradation of gels is continued by combination of reduction of azo crosslinkage and hydrolysis of amylose. The cumulative release ratios of Bovine serum albumin (BSA, as a model drug) loaded semi‐IPN gels are 25% in pH 2.2 buffer solutions and 74% in pH 7.4 buffer solutions within 48 h. Moreover, the release behavior of BSA from the semi‐IPN gels indicates that it follows Fickian diffusion mechanism in pH 2.2 media and non‐Fickian diffusion and polymer chains relaxation mechanism in pH 7.4 media. The results indicate that the release of BSA from the semi‐IPN gels was controlled via a combined mechanism of pH dependent swelling and specificity to enzymatic degradation. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Development of Sodium Carboxymethyl Cellulose-based Poly(acrylamide-co-2acrylamido-2-methyl-1-propane sulfonic acid) Hydrogels for In Vitro Drug Release Studies of Ranitidine Hydrochloride an Anti-ulcer Drug

The formation of sodium carboxymethyl cellulose (SCMC) based semi-interpenetrating networks (semi-IPN) with poly(acylamide-co-2-acrylamido-2-methy-l-propanesulfonic-acid) hydrogels. The hydrogels were prepared by free-radical polymerization using redox initiator. The characterizations of hydrogels were done by swelling experiments, FTIR spectroscopy and DSC analysis. Morphology of the samples were examined by SEM. Experimental results indicate that the semi-IPN hydrogel containing 0.10 g of SCMC and 5.829 mM of AMPS, shows the highest swelling capacity (64.83 g/g). The swelling behavior of the semi-IPN hydrogel (AS5) was studied in different pH solutions. The ranitidine hydrochloride drug loading and release of the semi-IPN hydrogels were studied by using a UV spectrophotometer.     

Irradiated Ch/GG/PVP-based stimuli-responsive hydrogels for controlled drug release

Hydrogels based on gamma (γ) irradiated chitosan (pre-irradiated), guar gum, and polyvinyl pyrrolidone were crosslinked with various concentrations of (3-mercapto propyl)trimethoxysilane and fabricated by solution casting technique for the drug delivery applications. High molecular weight chitosan (Ch) possesses lower solubility and higher viscosity, these problems overcame by γ irradiation, which also generated hydrophilicity and effect of irradiated Ch on controlled drug release was assessed. FTIR analysis showed the development of chemical and physical interactions and confirmed the incorporation of characteristic peaks. SEM micrographs revealed porous structure of the prepared hydrogels. Swelling analysis of the hydrogels was performed in distilled water, buffer, and electrolyte mediums. All the hydrogel samples showed higher swelling at acidic pH and lower swelling at neutral and basic pH. These pH-responsive characteristics made these RCGP hydrogels an important contender for injectable controlled drug release. The ampicillin sodium drug was loaded and in vitro controlled release mechanism was evaluated in the PBS, SIF, and SGF which shown out of all prepared hydrogels (RCGP-1, RCGP-2, and RCGP-3), RCGP-1 has exhibited 87.4% release in PBS and 81.3% in SIF in 180 min.