Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery

Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B12 and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B12 and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).     

pH dependent poly[2-(methacryloyloxyethyl)trimetylammonium chloride-co-methacrylic acid]hydrogels for enhanced targeted delivery of 5-fluorouracil in colon cancer cells

Stimuli responsive hydrogels have shown enormous potential as a carrier for targeted drug delivery. In this study we have developed novel pH responsive hydrogels for the delivery of 5-fluorouracil (5-FU) in order to alleviate its antitumor activity while reducing its toxicity. We used 2-(methacryloyloxyethyl) trimetylammonium chloride a positively charged monomer and methacrylic acid for fabricating the pH responsive hydrogels. The released 5-FU from all except hydrogel (GEL-5) remained biologically active against human colon cancer cell lines [HT29 (IC₅₀ = 110–190 μg ml^?1) and HCT116 (IC₅₀ = 210–390 μg ml^?1)] but not human skin fibroblast cells [BJ (CRL2522); IC₅₀ ≥ 1000 μg ml^?1]. This implies that the copolymer hydrogels (1–4) were able to release 5-FU effectively to colon cancer cells but not normal human skin fibroblast cells. This is probably due to the shorter doubling time that results in reduced pH in colon cancer cells when compared to fibroblast cells. These pH sensitive hydrogels showed well defined cell apoptosis in HCT116 cells through series of events such as chromatin condensation, membrane blebbing, and formation of apoptotic bodies. No cell killing was observed in the case of blank hydrogels. The results showed the potential of these stimuli responsive polymer hydrogels as a carrier for colon cancer delivery.     

Metformin hydrochloride-loaded poly(vinyl alcohol) composites as drug delivery systems

A straightforward method is proposed for the preparation of drug-loaded biocompatible polymer composites based on the freeze drying technique. The solution of poly(vinyl alcohol) (PVA) and metformin hydrochloride (MH) is frozen using liquid nitrogen and the ice crystals are removed by sublimation through freeze drying, which results in the formation of MH-loaded PVA composite. By controlling the PVA concentration in the solution, both MH-loaded PVA fibers and porous products can be obtained. The synthesized MH-loaded PVA composites are characterized with scanning electron microscopy (SEM), powder X-ray diffraction (XRD), Fourier-transformed infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The drug release behavior of the as-prepared products is studied to reveal their potential use in drug delivery system.     

Development and characterization of Poly (vinyl alcohol) based hydrogels for potential use as an articular cartilage replacement

Hydroxyapatite (HA) reinforced Poly(vinyl alcohol) (PVA) hydrogel composites has been proposed as a promising biomaterial to replace diseased or damaged articular cartilage. Here, PVA/in-situ produced HA hydrogels with 0, 3 and 7.5 wt.% of HA content were obtained by freezing/thawing technique. Thermal, structural and mechanical characterizations were carried out. SEM micrographs revealed that HA was homogeneously distributed in PVA until 3 wt.% whereas partial agglomeration was observed for higher contents (7.5 wt.%). No significant changes were observed in the glass transition temperature (the average value was near to 78 °C ± 3 °C), the melting point and structural water content whereas the gel fraction slightly increased (from 0.72 to 0.78) with the increase the content of HA. The absorbed water decreased (from 85.7% to 80.5%) as a function of HA content The stress–strain curves were really different in hydrated and non-hydrated conditions, changing from non-linear, in presence of water, to linear behavior in a dried state, being in the first case consistent with the articular cartilage . The lowest friction coefficient was obtained for samples with 3 wt. % HA (0.067 ± 0.049), which is, together with a high resistance (721 ± 25 kPa), an important property for materials that will be used as articular replacement. The results indicate that this hydrogel could be used, after other studies, as articular cartilage replacement.     

Poly(vinyl alcohol) hydrogels as hydrophilic matrices for the release of lipophilic drugs loaded in PLGA nanoparticles

Poly(vinyl alcohol) (PVA) hydrogels prepared by a freeze-thawing procedure were evaluated as matrices for the release of water-insoluble drugs such as dexamethasone. As it is impossible to directly entrap a lipophilic drug into a hydrophilic matrix, a novel mechanism has been designed based on producing biodegradable nanoparticles loaded with the drug, that could then be entrapped into the hydrogels. Nanoparticles were prepared by a solvent evaporation technique using a biodegradable copolymer of poly(lactic acid)-poly(glycolic acid) (PLGA). The effects of several processing parameters on particle properties were investigated. The drug release from free nanoparticles was compared to that from the nanoparticles entrapped into the PVA matrices. It was observed that the release profile of the drug is not significantly affected by the PVA matrix. A correlation was found between the amount of drug released and the PVA concentration in the hydrogels: the percentage of drug released, as a function of time, decreased by increasing PVA concentration, indicating that PVA concentration can be used as a tool in modulating the release of the drug.     

Antibiotic drug release behavior of poly (vinyl alcohol)/sodium alginate hydrogels

Poly (vinyl alcohol)/sodium alginate hydrogels were prepared by freeze-thaw followed by calcium ion crosslinking. Chloramphenicol release behavior from the poly (vinyl alcohol)/sodium alginate hydrogels in mimic conditions of gastrointestinal tract was examined. The effects of composition, number of freeze-thaw cycles and calcium ion concentration on drug release process were investigated. The results showed that the cumulative release amount of chloramphenicol from the hydrogels (crosslinked through 4 freeze-thaw cycles and immersed in 2 % calcium chloride solution) decreased from 84.3 % to 72.3 % as sodium alginate content increased from 0 % to 75 %. For the hydrogels containing 50 % sodium alginate and immersed in 2 % calcium chloride solution after the freeze-thaw cycles, cumulative release amount of chloramphenicol decreased from 83.5 % to 76.6 % as the freeze-thaw cycles increased from 2 to 6. Cumulative release amount of chloramphenicol from the hydrogels containing 50 % sodium alginate and with 4 freeze-thaw cycles decreased from 79.8 % to 75.6 % when concentration of calcium chloride solution increased from 1 % to 4 %.     

Poly (vinyl alcohol)/poly (acrylamide‐ co ‐diallyldimethyl ammonium chloride) semi‐IPN hydrogels for ciprofloxacin hydrochloride drug delivery

Herein, the authors developed a new and potential semi‐interpenetrating polymer network (semi‐IPN) hydrogels of poly vinyl alcohol (PVA), acryl amide and diallyldimethyl ammonium chloride employing chemical cross‐linker N, N''‐methylene bisacrylamide (NNMBA) and ammonium persulphate as an initiator by radical polymerisation. To analyse the copolymer formation between two monomers and IPN cross‐linking reaction, the resulting hydrogel was characterised by Fourier transform infrared spectroscopy and the surface morphology was analysed using scanning electron microscopy. Differential scanning calorimetry and X‐ray diffraction studies were also carried out for investigating drug loading and distribution and swelling experiments were carried out for the uptake of water. In vitro release of ciprofloxacin hydrochloride from hydrogel was performed at intestinal conditions. The amount of PVA, NNMBA and total monomer concentration was found to strongly control the drug release behaviour from the hydrogels.Inspec keywords: hydrogels, polymer blends, biomedical materials, drug delivery systems, polymerisation, Fourier transform infrared spectra, surface morphology, scanning electron microscopy, differential scanning calorimetry, X‐ray diffraction, swelling, biological organs, ammonium compoundsOther keywords: PVA‐poly(acrylamide‐co‐diallyldimethyl ammonium chloride) semiIPN hydrogels, ciprofloxacin hydrochloride drug delivery, semiinterpenetrating polymer network hydrogels, polyvinyl alcohol, acryl amide, diallyldimethyl ammonium chloride, chemical crosslinker N,N''‐methylene bisacrylamide, ammonium persulphate, radical polymerisation initiator, NNMBA, copolymer formation, IPN crosslinking reaction, Fourier transform infrared spectroscopy, surface morphology, scanning electron microscopy, differential scanning calorimetry, X‐ray diffraction, drug loading, drug distribution, swelling, water uptake, in vitro ciprofloxacin hydrochloride release, intestinal conditions, total monomer concentration, drug release behaviour     

Poly(vinyl alcohol)–hydroxyapatite biomimetic scaffold for tissue regeneration

Hydroxyapatite–poly(vinyl alcohol) composite blocks were produced by freeze–thawing in situ synthesized hybrid suspension. Matrix mediated precipitation of hydroxyapatite particles in the polymer, controlled the particle size in nanometer range (< 100 nm) and hydrogelation induced an ordered three-dimensional assembly of the particles. Morphological and crystallographic characterization revealed the formation of a macro-porous hydroxyapatite–poly(vinyl alcohol) nanocomposite block. Initial results indicate compositional dependence of modulus of elasticity of the composite.     

Structure Investigation of Poly(vinyl alcohol)-Collagen Composite

Naturally derived collagen protein was mixed thoroughly with medical grade poly (vinyl alcohol)(PVA) at the ratio of 90:10 (w/w) and was crosslinked by formaldehyde to form a homogeneous composite membrane. The buIk structure of the membrane was characterized ly means of Xray diffraction (XRD) and transmission electron microscoor (TEM). The membrane surface Structure was investigated using Fourier transform-infrared spectroscopy (attenuated totalrefraction) (FTIR-ATR), electron spectroscopy for chemical analysis (ESCA) and contact angle measurement. lt was found that collagen and PVA can remain Stable. This was supported by the fact that no sign of phase separation had been observed. The use of crosslinking agent can Substantially influence the Structure of the composite. It is suggested that this new compositedeserves further investigation and is potentially usable as a biomedical material.     

Poly(vinyl alcohol) as versatile biomaterial for potential biomedical applications

In this paper, we present some new case examples where the chemical versatility of poly (vinyl alcohol) (PVA) can be used for potential biomedical applications. PVA, the polymeric material used for designing new nanostructured devices, is water soluble, biocompatible and has excellent physical properties. We point out the possibility of obtaining wall-to-wall chemical hydrogels as well as microgels without diminishing the biocompatibility available in the starting PVA material. Injectability is another important factor to take into account in controlled drug delivery for gene therapy. In this respect, in this paper, established and more innovative methods are prospected in order to obtain particles with dimensions suitable for these applications.     

Investigation of swellable poly (N-isopropylacrylamide) based hydrogels for drug delivery

The thermo-sensitive properties of poly (N-isopropylacrylamide) (PNIPA) hydrogels are modified by the addition of hydrophilic acrylamide comonomers and an interpenetrating network of sodium alginate for drug delivery applications near 37 °C. A mathematical model is presented to describe the mass transport kinetics during the hydrogel drug delivery process, which is accompanied by a volume change during phase transition. In this model, the transport in the polymer matrix is described by Fick's second law in cylindrical coordinates, with concentration dependent diffusion coefficients. The moving boundary problems caused by the polymer matrix swelling are also solved by numerical simulation. The models show that the Trypan blue release from the modified PNIPA-based hydrogels is strongly concentration dependent. The sodium alginate component is also shown to effectively facilitate the diffusion process. The results from the simulation are in good agreement with the measurements of diffusion and swelling observed from in vitro experiments. The implications of this work are also discussed for practical drug delivery systems.     

Facile one-pot synthesis of iron oxide nanoparticles cross-linked magnetic poly(vinyl alcohol) gel beads for drug delivery

In this paper, a facile one-pot strategy for scalable synthesis of robust magnetic poly(vinyl alcohol) (mPVA) gel beads is developed. Through dropwise addition of mixed aqueous solution of iron salts and PVA solution into alkaline (e.g., ammonia, NaOH, and KOH) solution, mPVA gel beads with uniform size and excellent superparamagnetic property can be fabricated based on the simultaneous formation of magnetic iron oxide nanoparticles (MIONs) and cross-link of PVA chains. Moreover, this approach can be extended to prepare dual- or multiresponsive gel beads through simply adding functional fillers into PVA solution (e.g., mPVA-PNIPAM gel beads that possess both magnetic and temperature responsibilities can be readily prepared by adding temperature responsive poly(N-isopropylacrylamide) (PNIPAM) into PVA solution). It is found that that the obtained mPVA gel beads exhibit high drug loading level (e.g., above 70%) after the treatment of freezing-thawing. Drug release experiments reveal that the drug release rate and amount of the mPVA gel beads can be tuned by operating the external magnetic field and adjusting the concentration of iron oxide nanoparticles and temperature (for mPVA-PNIPAM gel beads). The present work is of interest for opening up enormous opportunities to make full use of magnetic gel beads in drug delivery and other applications, because of their facile availability, cost-effective productivity, and tunable drug release performance.     

Poly(vinyl alcohol) nanocomposite films containing chemically exfoliated molybdenum disulfide

Molybdenum disulfide (2H-MoS₂) was exfoliated in water after reaction with n-butyl-lithium. Using either alkaline or neutral conditions, different amounts of the resulting single-layer suspension were employed as filler for the production of poly(vinyl alcohol) films containing distinct disulfide contents. These nanocomposite films were obtained by wet casting and were further characterized by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) and Raman spectroscopies. The mechanical properties of the films were also evaluated. Characterization studies revealed the attainment of homogeneous nanocomposite films in both alkaline and neutral conditions, indicating good distribution and interaction of the hydrophilic filler with the polyhydroxylated polymer. Improved Young's (tensile) modulus (+57%) and tensile strength (+9%) as well as reduced elongation (−78%) were achieved only when the neutral suspension of single layers was utilized. Increased MoS₂ content diminished the crystallinity of the polymer, while enhanced mechanical properties were obtained in the presence of intermediate filler content (around 1 wt%).     

Development of polysaccharide-based colon targeted drug delivery systems for the treatment of amoebiasis

The main focus of this study is to develop colon targeted drug delivery systems for metronidazole (MTZ). Tablets were prepared using various polysaccharides or indigenously developed graft copolymer of methacrylic acid with guar gum (GG) as a carrier. Various polysaccharides such as GG, xanthan gum, pectin, carrageenan, β-cyclodextrin (CD) or methacrylic acid-g-guar (MAA-g-GG) gum have been selected and evaluated. The prepared tablets were tested in vitro for their suitability as colon-specific drug delivery systems. To further improve the colon specificity, some selected tablet formulations were enteric coated with Eudragit-L 100 to give protection in an acidic environment. Drug release studies were performed in simulated gastric fluid (SGF) for 2 hr followed by simulated intestinal fluid (SIF) at pH 7.4. The dissolution data demonstrate that the rate of drug release is dependent upon the nature and concentration of polysaccharide/polymer used in the formulations. Uncoated tablets containing xanthan gum or mixture of xanthan gum with graft copolymer showed 30-40% drug release during the initial 4-5 hr, whereas for tablets containing GG with the graft copolymer, it was 70%. After enteric coating, the release was drastically reduced to 18-24%. The other polysaccharides were unable to protect drug release under similar conditions. Preparations with xanthan gum as a matrix showed the time-dependent release behavior. Further, in vitro release was performed in the dissolution media with rat caecal contents. Results indicated an enhanced release when compared to formulations studied in dissolution media without rat caecal contents, because of microbial degradation or polymer solubilization. The nature of drug transport was found to be non-Fickian in case of uncoated formulations, whereas for the coated formulations, it was found to be super-Case-II. Statistical analyses of release data indicated that MTZ release is significantly affected by the nature of the polysaccharide used and enteric coating of the tablet. Differential scanning calorimetry indicated the presence of crystalline nature of drug in the formulations.     

Strong dual-crosslinked hydrogels for ultrasound-triggered drug delivery

Nano Research - Hydrogels that can respond to dynamic forces either from endogenous biological activities or from external mechanical stimuli show great promise as novel drug delivery systems...     

Stimuli-responsive bacterial cellulose-g-poly(acrylic acid-co-acrylamide) hydrogels for oral controlled release drug delivery

This study evaluated the potential of stimuli-responsive bacterial cellulose-g-poly(acrylic acid-co-acrylamide) hydrogels as oral controlled-release drug delivery carriers. Hydrogels were synthesized by graft copolymerization of the monomers onto bacterial cellulose (BC) fibers by using a microwave irradiation technique. The hydrogels were characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). FT-IR spectroscopy confirmed the grafting. XRD showed that the crystallinity of BC was reduced by grafting, whereas an increase in the thermal stability profile was observed in TGA. SEM showed that the hydrogels exhibited a highly porous morphology, which is suitable for drug loading. The hydrogels demonstrated a pH-responsive swelling behavior, with decreased swelling in acidic media, which increased with increase in pH of the media, reaching maximum swelling at pH 7. The release profile of the hydrogels was investigated in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The hydrogels showed lesser release in SGF than in SIF, suggesting that hydrogels may be suitable drug carriers for oral controlled release of drug delivery in the lower gastrointestinal tract.     

Poly(vinyl alcohol) reinforced with large-diameter carbon nanotubes via spray winding

For practical application of carbon nanotube (CNT)/polymer composites, it is critical to produce the composites at high speed and large scale. In this study, multi-walled carbon nanotubes (MWNTs) with large diameter (∼45 nm) and polyvinyl alcohol (PVA) were used to increase the processing speed of a recently developed spraying winding technique. The effect of the different winding speed and sprayed solution concentration to the performance of the composite films were investigated. The CNT/PVA composites exhibit tensile strength of up to 1 GPa, and modulus of up to 70 GPa, with a CNT weight fraction of 53%. In addition, an electrical conductivity of 747 S/cm was obtained for the CNT/PVA composites. The good mechanical and electrical properties are attributed to the uniform CNTs and PVA matrix integration and the high degree of tube alignment.