Electrosprayed poly(vinyl alcohol) particles: preparation and evaluation of their drug release profile

Encapsulation of bioactive molecules within polymeric particles is a challenge because of several limitations, including low drug‐loading efficiency, unwanted release profile, polydispersity and batch‐to‐batch variation in reproducibility, along with the limitations of scaling up the process. It is essential to control the morphology of pure polymer particles in the first instance, in order to obtain the desired release profile of drugs from the particles during a later stage. Here we report the preparation of electrosprayed particles from a water‐soluble US Food and Drug Administration‐recognized polymer, namely poly(vinyl alcohol) (PVA), as an approach towards a short‐term drug delivery vehicle. Through electrospraying and varying the solvent ratios, three different sizes of particles were prepared, with sizes ranging from 500 to 2000 nm. Insulin was chosen as a model bioactive molecule, and the release profile of the drug was studied after its incorporation in the PVA particles. Fractional release plots obtained showed short‐term release of insulin within the first 60 min. Release curves were analyzed according to the Ritger–Peppas model, suggesting Fickian diffusion as the predominant insulin release mechanism from the PVA particles. This work suggests electrosprayed PVA particles as an innovative drug delivery system for short‐term administration of drugs. © 2015 Society of Chemical Industry     

Mechanical reinforcement of hydrogels by nanofiber network undergoing biaxial deformation

Hydrogels can encapsulate large quantities of water within a three‐dimensional crosslinked polymer network. Polyvinyl alcohol (PVA) hydrogels have been widely used in tissue engineering, wound dressing, and drug delivery. However, the inferior mechanical properties of PVA hydrogels limit their utility in load‐bearing applications. To alleviate this deficiency, we used a hybrid electrospinning/solution casting continuous process to reinforce PVA hydrogels using polyurethane nanofibers. In this process, the nanofibers were electrospun into the wet solution cast film prior to solidification. The reinforcement of PVA hydrogels at a series of extent of water swelling was determined using a custom built bubble biaxial stretching device. The results showed that nanofibers have substantial enhancement effect on mechanical properties particularly in thin hydrogel films at high water concentrations. Reduction of nanofiber diameter was also found to increase this reinforcement due to increased interfacial area between nanofibers and hydrogels. POLYM. COMPOS., 37:709–717, 2016. © 2014 Society of Plastics Engineers     

Preparation of novel bilayer hydrogels by combination of irradiation and freeze–thawing and their physical and biological properties

BACKGROUND: Hydrogels made by irradiation or freeze–thawing often exhibit poor mechanical strength; therefore we investigated a novel synthetic method to circumvent this detrimental effect. We report a series of novel bilayer poly(vinyl alcohol) (PVA)/water‐soluble chitosan (ws‐chitosan)/glycerol hydrogels prepared by a combination of irradiation and freeze–thawing. Scanning electron microscopy morphology, swelling behavior, mechanical strength, elongation at break, PVA dissolution behavior and bovine serum albumin (BSA) release profile of the bilayer hydrogels were compared with those of hydrogels made by irradiation and freeze–thawing followed by irradiation. The cytotoxicity of the bilayer hydrogels was studied using a tetrazolium salt (MTT) assay. RESULTS: The novel bilayer hydrogels contain one layer made by freeze–thawing followed by irradiation and the other layer made by irradiation. The preparation method provides the two layers with good combination force in the wet state. However, the two layers are not combined very well in the freeze‐dried state due to the difference in microstructure. The bilayer hydrogels have large swelling capacity and good mechanical strength, and these properties can be varied by changing freeze–thawing cycles, irradiation doses and the relative thickness of the two layers. The PVA and BSA release behaviors show that the bilayer hydrogels have a small amount of dissolved PVA and can prolong the BSA release time. The MTT assay shows that extracts of the bilayer hydrogels are non‐toxic towards L929 mouse fibroblasts. CONCLUSION: The novel bilayer hydrogels prepared in this study show good physical properties with no cytotoxicity, indicating that they are suitable for biomedical applications, such as in wound dressings and drug delivery devices. Copyright © 2009 Society of Chemical Industry     

Dual-responsive release behavior of pH-sensitive PVA/PAAc hydrogels containing temperature-sensitive PVA/PNIPAAm microcapsules

Both temperature and pH responsive drug delivery system was prepared by combining temperature-sensitive poly(vinyl alcohol) (PVA)/poly(N-isopropylacrylamide) (PNIPAAm) microcapsules and pH-sensitive PVA/poly(acrylic acid) (PAAc) hydrogels. The release of drug from the composite hydrogels increased as the pH increased due to the repulsion among the carboxylate anions in the PVA/PAAc hydrogels. The release of drug from the composite hydrogels also increased as the temperature decreased due to the higher hydrophilicity generated below the lower critical solution temperature of PNIPAAm. The compression moduli of composite hydrogels increased with increasing the content of PVA/PNIPAAm microcapsules. The biocompatibility of composite hydrogels was confirmed by the cytotoxicity test.     

Covalently cross‐linked and hydrophobically modified alginic acid hydrogels and their application as drug carriers

Covalently crosslinked and hydrophobically modified alginate hydrogels were prepared through esterification of alginic acid (ALG‐H) with 1,10‐decanediol that functioned as a crosslinking agent and hydrophobic component. The preparation was accomplished with one step and was carried out in N,N‐dimethylformamide solution at a reduced pressure for removing the water produced. The characterization results confirmed the esterification of the products. The modified alginate hydrogels could be used as drug delivery vehicles for controlled release. The drug release study revealed that compared with a calcium alginate hydrogel the modified hydrogels possessed improved loading rate and encapsulation efficiency for the hydrophobic drug(ibuprofen), and a remarkable sustained release behavior was observed. The release kinetics was close to zero order, a desirable drug release pattern. The modified alginate hydrogels were nontoxic and were potentially applicable as a promising biomaterial. POLYM. ENG. SCI., 2013. © 2012 Society of Plastics Engineers     

Preparation and characterization of PVA films with magnetic nanoparticles: The effect of particle loading on drug release behavior

This article deals with the drug release behavior of theophylline (Th) from poly(vinyl alcohol) (PVA) hydrogels, prepared with magnetic nanoparticles at different particle loadings. These biocompatible matrices were obtained by incorporating different amounts of an aqueous ferrofluid into PVA hydrogels, loaded with Th as a marker for drug‐delivery studies. PVA films with magnetic particles proved to be magnetic field‐responsive materials as the drug release decreased through the application of a relative low and uniform magnetic field for particle concentrations of 0.9% w/w or higher. Moreover, the percentage of restriction of drug release is found to be correlated with particle loading. The in vitro release profiles were analyzed by applying a semiempirical power law to obtain the kinetic parameters. The value of the release exponent was found to be in the range 0.54–0.56 in all experiments, which thus indicates a predominant diffusional mechanism for drug release from these smart magnetic hydrogels. This effect suggests the possibility of modulating the release behavior by controlling the particle content in the preparation of the composites. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Exploring poly(vinyl alcohol) hydrogels containing drug–cyclodextrin complexes as controlled drug delivery systems

Poly(vinyl alcohol) (PVA) hydrogels containing drug–β‐cyclodextrin inclusion complexes (ICs) were synthesized with glutaraldehyde (GA) as a crosslinker. The role of cyclodextrin (CD), the effect of the nature of drug, and the degree of crosslinking on the drug‐release process were investigated. The probable mechanism of drug release was also explored. Controlled release of the drug was achieved from the hydrogels containing the ICs. The nature of the drug, in terms of its binding efficacy with CD, played an important role. The effect of the degree of crosslinking on the release pattern was strikingly different from that in the hydrogels containing free drug and those with ICs. The role of CD in the drug‐release process was not only due to its inclusion ability but also its effect on the polymer relaxation. GA, apart from crosslinking PVA, probably interacted with the cyclodextrins and, thereby, influenced the matrix structure and the drug‐release kinetics. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40318.     

Drug‐release behavior of chitosan‐g‐poly(vinyl alcohol) copolymer matrix

Chitosan‐g‐poly(vinyl alcohol) (PVA) copolymers with different grafting percent were prepared by grafting water‐soluble PVA onto chitosan. The drug‐release behavior was studied using the chitosan‐g‐PVA copolymer matrix containing prednisolone in a drug‐delivery system under various conditions. The relationship between the amount of the released drug and the square root of time was linear. From this result, the drug‐release behavior through the chitosan‐g‐PVA copolymer matrix is shown to be consistent with Higuchi's diffusion model. The drug‐release apparent constant (K_H) was slightly decreased at pH 1.2, but increased at pH 7.4 and 10 according to the increasing PVA grafting percent. Also, K_H was decreased by heat treatment and crosslinking. The drug release behavior of the chitosan‐g‐PVA copolymer matrix was able to be controlled by the PVA grafting percent, heat treatment, or crosslinking and was also less affected by the pH values than was the chitosan matrix. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 458–464, 1999     

Semi-IPN hydrogels based on Poly(vinyl alcohol) for controlled release studies of chemotherapeutic agent and their Swelling characteristics

Poly (vinyl alcohol)/poly(acryl amide-co-acrylamidoglycolic acid) (PVA/Poly(Am-co-AGA) based pH sensitive semi interpenetrating (semi-IPN) hydrogels were prepared by free radical polymerization in aqueous solution using N, N-methelene-bis-acryl amide (MBA) as a crosslinker. Different hydrogels with different compositions of AGA and MBA were prepared and characterized by Fourier transform infrared spectroscopy. The developed hydrogels were used for controlled release of 5-fluorouracil (5-FU). The drug entrapment efficiency up to 55% was achieved. The 5-FU loaded gels were characterized by X- ray diffraction and differential scanning calorimetric techniques, to understand the nature of drug in the polymeric matrix. The release of 5-FU through the semi-IPN was completed with in ∼12 h. Swelling studies performed in water have been analyzed with the help of an empirical equation to investigate the diffusion mechanism.     

Surface Cross-Linked Poly (Vinyl Alcohol) Hydrogel for Colon Targeted Drug Release

A series of surface cross-linked PVA hydrogels (previously bulk cross-linked with maleic anhydride) were prepared for different cross-linker (glutaraldehyde) concentration. FTIR-ATR study revealed the cross-linking reaction. Surface cross-linking results in contraction of pores and increase in hydrophobicity, pore tortuosity around the surface of the membrane. As a result swelling, drug release decreases with increasing glutaraldehyde concentration. After surface cross-linking swelling of the hydrogels in simulated gastric fluid (SGF) further decreased to attain half of the value as observed for only bulk cross-linked membranes. Surface cross-linking has improved the colon-targeted release characteristics of the drugs from the PVA hydrogels.     

Double‐network hydrogel with high mechanical strength prepared from two biocompatible polymers

Novel double‐network (DN) hydrogels with high mechanical strength have been fabricated with two biocompatible polymers, poly(vinyl alcohol) (PVA) and poly(ethylene glycol) (PEG), through a simple freezing and thawing method. Some properties of the obtained hydrogels, such as the mechanical strength, rheological and thermodynamic behavior, drug release, and morphology, have been characterized. The results reveal that in sharp contrast to most common hydrogels made with simple natural or synthetic polymers, PVA/PEG hydrogels can sustain a compressive pressure as high as several megapascals, highlighting their potential application as biomedical materials. In addition, a model for describing the structural formation of PVA/PEG DN hydrogels is proposed: the condensed PVA‐rich phase forms microcrystals first, which bridge with one another to form a rigid and inhomogeneous net backbone to support the shape of the hydrogel, and then the dilute PEG‐rich phase partially crystallizes among the cavities or voids of the backbone; meanwhile, there are entanglements of molecular chains between the two polymers. Moreover, a mechanism is also proposed to explain the high mechanical strength of PVA/PEG DN hydrogels. It is suggested that the free motion of PEG clusters in the cavities of PVA networks can prevent the crack from growing to a macroscopic level because the linear PEG chains in the cavities effectively absorb the crack energy and relax the local stress either by viscous dissipation or by large deformation of the PEG chains. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Synthesis and characterization of cetirizine‐containing,pH‐sensitive acrylic acid/poly(vinyl alcohol) hydrogels

In this study, interpenetrated acrylic acid (AA)/poly(vinyl alcohol) (PVA) hydrogels were prepared by free‐radical polymerization with N,N‐methylene bisacrylamide (MBAAm) as a crosslinker. The basic structural parameters, such as the molecular weight between crosslinks, volume interaction parameter, number of crosslinks, Flory–Huggins solvent interaction parameter, and diffusion coefficient, were calculated. Cetirizine dihydrochloride was loaded as a model drug in selected samples. The prepared hydrogels were evaluated for swelling, sol–gel fraction, and porosity. The swelling of the AA/PVA hydrogels was found to be directly proportional to the pH, that is, 1.2–7.5, depending on composition. The percentage of cetirizine hydrochloride was found to be directly proportional to the buffer pH and was at its maximum at pH 7.5, that is, 90–95%, and its lowest at pH 1.2, that is, 20–30%. The gel fraction increased with increasing concentration of AA and MBAAm, whereas the porosity showed the same response with AA, but an inverse relationship was observed with MBAAm. The drug‐release data were fitted into various kinetics models, including the zero‐order, first‐order, Higuchi, and Peppas models, which showed non‐Fickian diffusion. The prepared hydrogels were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy, and no interaction was found among the polymer ratio and the drug. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43407.     

Preparation and antibacterial effects of PVA‐PVP hydrogels containing silver nanoparticles

The poly(vinyl alcohol)/poly(N‐vinyl pyrrolidone) (PVA–PVP) hydrogels containing silver nanoparticles were prepared by repeated freezing–thawing treatment. The silver content in the solid composition was in the range of 0.1–1.0 wt %, the silver particle size was from 20 to 100 nm, and the weight ratio of PVA to PVP was 70 : 30. The influence of silver nanoparticles on the properties of PVA–PVP matrix was investigated by differential scanning calorimeter, infrared spectroscopy and UV–vis spectroscopy, using PVA–PVP films containing silver particles as a model. The morphology of freeze‐dried PVA–PVP hydrogel matrix and dispersion of the silver nanoparticles in the matrix was examined by scanning electron microscopy. It was found that a three‐dimensional structure was formed during the process of freezing–thawing treatment and no serious aggregation of the silver nanoparticles occurred. Water absorption properties, release of silver ions from the hydrogels and the antibacterial effects of the hydrogels against Escherichia coli and Staphylococcus aureus were examined too. It was proved that the nanosilver‐containing hydrogels had an excellent antibacterial ability. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 125–133, 2007     

pH-sensitive IPN hydrogel based on poly (aspartic acid) and poly (vinyl alcohol) for controlled release

Various pH-sensitive sequential interpenetrating polymer network (IPN) hydrogels were prepared by introducing poly (vinyl alcohol) (PVA) hydrogel into Poly (aspartic acid) (PASP) hydrogel by freeze-thawing treatment to obtain a novel drug delivery system to the intestine. The structure and the morphologies of the prepared hydrogels were studied by Fourier Transform Infrared Spectroscopy (FTIR) and scanning electron microscopy (SEM). The thermal behavior and crystallinity of the hydrogels were characterized by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Their pH-sensitive properties moreover were studied and the results revealed that both PASP hydrogel and IPN hydrogels exhibited excellent pH-sensitivity. Furthermore, the controlled drug release properties of the hydrogels were also evaluated and results indicated that by increasing the PVA fraction in the IPN hydrogel, the release of Naproxen sodium was improved. These results show that the IPN hydrogels could be a suitable carrier for site-specific drug delivery in the intestine.     

Preparation and properties of physically crosslinked sodium carboxymethylcellulose/poly(vinyl alcohol) complex hydrogels

A series of physically crosslinked complex hydrogels of poly(vinyl alcohol) (PVA) and sodium carboxymethylcellulose (CMC) were prepared via physical mixing and a freeze/thaw technique. The morphology of the CMC/PVA complex gels was analyzed with differential scanning calorimetry and wide‐angle X‐ray diffraction. It was found that the crystallinity and melting temperature of the complex gels decreased, whereas the glass‐transition temperature increased, with an increase in the content of CMC. The reswelling of the complex gels was pH‐responsive and relied on the content of CMC and the freeze/thaw cycles. A network structure model of the complex gel was presented. PVA crystalline regions served as physical crosslinks; the interaction between CMC and PVA resulted in intramolecular entanglements. It was also found that the model drug hemoglobin was released completely from the complex hydrogels in 4 h, and its release rate increased with an increase in the content of CMC. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Properties of hydrogels of atactic poly(vinyl alcohol)/NaCl/H2O system and their application to drug release

In order to prepare cost‐effective physically cross‐linked hydrogels including food salt sodium chloride, samples, were prepared with various concentrations of NaCl and respective atactic poly(vinyl alcohol) (a‐PVA), and were evaluated. It had been observed that hydrogels containing NaCl concentration (9–11 wt%) along with a‐PVA concentration 9–5% respectively exhibited higher melting points (91.5–95.1 °C). A higher melting point characterizes the hydrogel composition of a system like a‐PVA(7%)/NaCl(11%)/H₂O. The swelling degree of this hydrogel was found to be comparatively better at 37 °C than at any other temperature studied here. However, irregular Fickian swelling was found at this temperature. The UV light absorption maximum at 362–364 nm and minimum at 351 nm for this hydrogel had been found as evidence of physical cross‐linking. A drug, theophylline was loaded by solvent‐sorption and feed‐mixture dissolving methods. The feed‐mixture dissolving method is better than solvent sorption because of high drug loading, comparatively low fraction release rate and more sustained‐release of drug than that of solvent‐sorption. Theophylline was released twice as fast from the hydrogel after solvent‐sorption drug loading (3 h) than from that which used the feed‐mixture dissolving method (6.5 h). Theophylline‐loaded hydrogels of this system (feed‐mixture dissolving) were then prepared at high temperature (60 °C) thawing for 6 h followed by chilling at 0.4 °C for 3 h as one cycle. And the drug release behaviour and mass transfer were found almost the same as for chilling (24 h at 0.4 °C)–thawing (48 h at room temperature). Drug release behaviour was studied as apparently irregular Fickian diffusion (Higuchi Matrix Dissolution Model). © 2002 Society of Chemical Industry     

Gelation of a new hydrogel system of atactic‐poly(vinyl alcohol)/NaCl/H2O

a‐PVA/NaCl/H₂O hydrogels have been prepared by gelation of aqueous atactic‐poly(vinyl alcohol) (a‐PVA) solutions in the presence of NaCl. The gelling temperature, melting temperature and the preservation of water of the hydrogels have been measured. The effect of the addition of NaCl to the hydrogels on gelling temperature and melting temperature is marked when the NaCl concentration is over a certain value. High NaCl concentration favours high‐melting‐point hydrogels. When the NaCl concentration is high enough (such as 11%), high‐melting‐point and white turbid opaque a‐PVA/NaCl/H₂O hydrogels can be prepared, regardless of the PVA concentration. Similarly, the low gelling temperature of a‐PVA/NaCl/H₂O solutions comes from low NaCl concentration, while high gelling temperature ranges from 50 to 70 °C when the NaCl concentration is 11%. In appearance, the types of syneresis of a‐PVA/NaCl/H₂O are χ‐type or a mixture of χ‐ and n‐types; water release of the hydrogels is slowed down by the addition of NaCl. © 2002 Society of Chemical Industry     

Preparation and characterization of novel cationic copolymer hydrogels with pH sensitivity and thermosensitivity

Cationic hydrogels were synthesized through the copolymerization of N‐isopropylacrylamide and dimethylaminoethylmethacrylate. N,N′‐Methylenebisacrylamide was used as a crosslinking agent, and sodium bisulfite/ammonium persulfate was used as an initiator. The equilibrium and dynamic swelling properties were investigated to reveal the pH sensitivity and thermosensitivity of the hydrogels. The conclusion was drawn that the prepared cationic hydrogels demonstrated critical sensitivity at 37°C and pH 7.0–8.0 and that the stronger the acidity was of the buffered solution, the shorter the equilibrium swelling time was of the hydrogels. Drug‐release experiments in vitro were carried out at 37°C (close to body temperature), at pH 1.4 (close to the pH of the stomach), and at pH 7.4 (close to the pH of the intestine). The release results indicated that the drug (chloramphenicol) was released more rapidly from the prepared hydrogel in a pH 1.4 buffered solution than in a pH 7.4 one, and this was consistent with the results predicted from the experiments of the swelling kinetics. Moreover, the drug‐release process was confirmed by scanning electron micrographs of the hydrogels embedded with chloramphenicol. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 3602–3608, 2006     

Thermally crosslinked anionic hydrogels composed of poly(vinyl alcohol) and poly(γ‐glutamic acid): Preparation,characterization, and drug permeation behavior

pH‐sensitive anionic hydrogels composed of poly(vinyl alcohol) (PVA) and poly(γ‐glutamic acid) (γ‐PGA) were prepared by the freeze drying method and thermally crosslinked to suppress hydrogel deformation in water. The physical properties, swelling, and drug‐diffusion behaviors were characterized for the hydrogels. In the equilibrium swelling study, PVA/γ‐PGA hydrogels shrunk in pH regions below the pK_a (2.27) of γ‐PGA, whereas they swelled above the pK_a. In the drug‐diffusion study, the drug permeation rates of the PVA/γ‐PGA hydrogels were directly proportional to their swelling behaviors. The cytocompatibility test showed no cytotoxicity of the PVA/γ‐PGA hydrogels for the 3T3 fibroblast cell lines. The results of these studies suggest that hydrogels prepared from PVA and γ‐PGA could be used as orally administrable drug‐delivery systems. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Preparation and characterization of nanoparticulate poly(N‐isopropylacryl‐ amide) hydrogel for the controlled release of anti‐tumour drugs

BACKGROUND: Poly(N‐isopropylacrylamide) (PNIPA) nanohydrogels were synthesized by inverse microemulsion to be used for the controlled release of anti‐tumour drugs. Different methods were used to obtain drug‐loaded xerogels, and their effect on drug release was studied, and evaluated using mathematical modelling. RESULTS: Nanoparticulate hydrogels, with a z‐average diameter of 170 nm, were loaded with 5‐fluorouracil (5‐FU), methotrexate (MTX) or mitomycin C (MMC) by using spray drying (SD) and freeze drying (FD). Xerogels obtained by SD consisted of individual and independent particles, whereas particles established interactions in xerogels obtained by FD. Total drug release took place at 6 and 7 h from 5‐FU‐loaded and MMC‐loaded xerogels prepared by SD, whereas MTX was expelled from the xerogels formed using the SD process. Drug release was slower from xerogels prepared by FD: 5‐FU at 32 h, MMC at 120 h and MTX at 240 h. The Higuchi model most aptly fits the dissolution data. Non‐Fickian and Fickian release behaviour can be attributed to SD and FD formulations, respectively. CONCLUSION: The amount of drug loaded, the morphology of xerogels as well as the drug release characteristics not only depend on the drug but also mainly on the process used to obtain the drug‐loaded PNIPA xerogels. Copyright © 2008 Society of Chemical Industry