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PubMed2002

Effect of polyvinyl alcohol (PVA) concentration during vitrification of in vitro matured bovine oocytes.

Polyvinyl alcohol (PVA) was used as a substitute for serum in a vitrification solution for in vitro matured bovine oocytes. In vitro matured bovine oocytes were cryopreserved in various vitrification solutions (VS) supplemented with different concentrations (0.05, 0.1, 0.5, and 1%) of PVA, 20% fetal calf serum (FCS) or without macromolecule supplementation in a gel-loading tip (GL-tip). After warming, vitrified oocytes were examined for effects on survivability, fertilizability, and embryonic development in vitro. At 18 h in vitro fertilization after vitrifying and warming, the number of surviving mature oocytes vitrified in VS without macromolecule supplementation was significantly (P < 0.05) lower than those with macromolecule supplementation. For fertilizability after vitrification, there was no significant difference in the penetration rate of oocytes among fresh oocytes (98.7%); oocytes vitrified in VS supplemented with 0.1 (76.8%), 0.5 (70.2%), or 1% (80.3%) PVA; 20% (84.1%) FCS; or without supplementation (61.7%). Also, the normal fertilization rate was not significantly different in oocytes vitrified with 0.1 (56.5%), 0.5 (43.5%), or 1% (49.7%) PVA and 20% (60.6%) FCS, compared with fresh oocytes (84.0%). Subsequently, vitrified oocytes were examined for embryonic development effects in vitro. The highest proportion of cleaved oocytes after vitrification was obtained in VS supplemented with 0.1% (18.8%) PVA. Additionally, the proportion of development to morula stage (7.7%) in the oocytes vitrified in a VS supplemented with 0.1% PVA was significantly (P < 0.05) superior to that of the 0, 0.5, and 1% PVA-vitrified groups. However, the beneficial effect of PVA addition was not found in blastocyst development. Embryonic development of vitrified oocytes was significantly lower than that of fresh oocytes. In conclusion, the present results indicate that 0.1% PVA supplementation in VS results in a significantly higher rate of morula stage embryos than 0, 0.5, and 1% PVA supplementation, and could replace FCS in VS for vitrification of in vitro matured bovine oocytes.

Animals↗
PubMed2004

Amino acid metabolism of preimplantation bovine embryos cultured with bovine serum albumin or polyvinyl alcohol.

Bovine serum albumin (BSA) is an embryotrophic macromolecule used in embryo culture media, which is commonly replaced with synthetic compounds, such as polyvinyl alcohol (PVA). This study compared the effect of BSA and PVA on the development, blastocyst cell number and amino acid metabolism of preimplantation bovine embryos in vitro. Embryos were produced by in vitro maturation and fertilization of immature oocytes from abattoir-derived ovaries. Zygotes were cultured in synthetic oviduct fluid with either 4 mg/ml BSA (SOFaaBSA) or 1 mg/ml PVA (SOFaaPVA) in microdrops with a mineral oil overlay at 39 degrees C under a 5% O2/5% CO2/90% N2 atmosphere. Blastocyst rate and cell numbers were determined after 123 h of culture. In parallel, single expanding blastocysts grown in either medium were incubated in microdrops for 12 h. Amino acid profile of spent drops was determined by high performance liquid chromatography. Replacing BSA with PVA depressed blastocyst rate and cell numbers, and led to quantitative and qualitative differences in amino acid appearance, disappearance and turnover. These differences could partly be due to an increase in free intracellular amino acid concentration in SOFaaBSA embryos derived from hydrolysis of endocytosed BSA, and argue against the inclusion of PVA in bovine embryo culture media.

Amino Acids↗
PubMed2002

Photocrosslinkable polyvinyl alcohol hydrogels that can be modified with cell adhesion peptides for use in tissue engineering.

Photoactive polyvinyl alcohol hydrogels (PVA) have been investigated for use as tissue engineering scaffolds. These materials allow in situ polymerization for minimally invasive implantation methods. The mechanical properties of these materials can be tailored for a variety of soft tissue applications. The Young's modulus and ultimate tensile strength of PVA hydrogels are increased with increasing polymer concentration, and highly elastic hydrogels can be formed by altering the number of crosslinkable groups per chain. Fibroblasts homogeneously seeded within 3 mm thick PVA hydrogels remained viable throughout 2 weeks in culture, with no differences in viability across the thickness of the hydrogel. Cells seeded within the PVA hydrogels also produce extracellular matrix proteins, as indicated by the production of hydroxyproline during culture. Intrinsically cell non-adhesive, these PVA hydrogels were functionalized with the cell-adhesive peptide RGDS and found to support the attachment and spreading of fibroblasts in a dose-dependent manner. These results suggest that photopolymerizable PVA hydrogels are promising for tissue engineering applications.

Biocompatible Materials↗
PubMed2003

Preliminary study of polyvinyl alcohol-hydrogel (PVA-H) artificial meniscus.

Nowadays the importance of knee meniscal function is recognized. The treatment for meniscus injury has been changing from resection to repair. However, depending on the type of injury, meniscectomy cannot be avoided. In consideration of the prognosis in such patients, we developed artificial meniscus using polyvinyl alcohol-hydrogel (PVA-H) with a high water content and performed an animal experiment as preliminary study. In the experiment using rabbits, the lateral meniscus was replaced with an artificial meniscus in one knee side and lateral meniscectomy was performed in another knee side of each rabbit. In the knees treated by artificial meniscus replacement, regressive changes were initially observed but did not progress after a certain period, and the articular cartilage state was good even after 1 year. In addition, neither wear nor breakage of PVA-H was observed. These results suggest that artificial meniscus using PVA-H with a high water content compensates for meniscus function and is clinically applicable. However, for clinical application some problems such as fixation method, tolerance of PVA-H, remain to be solved.

Animals↗
PubMed1999

Characterization of transient platelet contacts on a polyvinyl alcohol hydrogel by video microscopy.

Acridine orange labelled, washed human platelets were counted and tracked on polyvinyl alcohol (PVA), heparin-PVA and polyethylene (PE)-coated coverslips with a view to understand why transient contact on the PVA hydrogels lead to elevated platelet activation and consumption relative to polyethylene. Over the 4 min of initial contact that was studied, platelet adhesion was higher on PE than on PVA or heparin-PVA at both 40 and 200 s(-1), as expected, regardless of whether the surfaces were pre-treated with albumin or fibrinogen. Not all platelets appearing to make contact with the surface, actually attached. For example, less than 2% of the platelets contacting albumin pre-treated PVA (at 40 s(-1)) remained adherent at the end of the initial 60 s observation time, while the corresponding number for PE was greater than 9%. A greater fraction of the platelets remained adherent at the higher shear rate or with fibrinogen pre-treatment, but the difference between PVA and PE remained similar: for example, with fibrinogen pre-treatment at 200 s(-1), approximately 25% of the platelet contacts resulted in adhesion on PVA while 66% did so on PE. While net platelet adhesion was less for the hydrogels, than for PE, the total number of contacts (adherents + non-adherents) were more comparable and unexpectedly higher for albumin pre-treatment than for fibrinogen. Net platelet adhesion is but one component of the total platelet interaction with a material surface. Fluorescent video microscopy has been shown to be a useful, albeit not unequivocal, method for assessing the platelets that make contact with but do not adhere to a surface. reserved

Biocompatible Materials↗
PubMed1998

Spectroscopic manifestations of flavomononucleotide dimers in polyvinyl alcohol films.

Absorption and fluorescence spectra of flavomononucleotide (FMN) in polyvinyl alcohol films (PVA) over a very wide concentration range are investigated. The dimerization constant as well as the pure monomer and dimer spectra are calculated and the structural parameters of FMN dimer are established. Excitation wavelength and temperature dependencies of FMN/PVA fluorescence spectra for different FMN concentrations were carried out. These measurements together with those of absorption reveal that dimers are imperfect traps for excitation energy and that the energy transfer can occur both in forward and in reverse direction. Moreover, it was shown that the observed temperature changes in fluorescence spectra may be qualitatively explained by the effect of inhomogeneous broadening of FMN energy levels and by the presence of fluorescent dimers.

Dimerization↗
PubMed2000

Polymer coating of liposomes with a modified polyvinyl alcohol and their systemic circulation and RES uptake in rats.

The objective of this study was to evaluate the in vivo characteristics of liposomes coated with a polyvinyl alcohol having a long alkyl chain at the end of the molecule (PVA-R) as an injectable drug carrier for passive targeting of drugs. A fluorescence marker, cholesteryl-anthracene-9-carboxylate, was incorporated into the liposomes to detect their concentration in the plasma and organs. The small unilamellar liposomes (100 nm in diameter) with various lipid compositions, such as the different cholesterol contents or the different charges, were prepared by the hydration method followed by sonication and coated with PVA or PVA-R by just mixing the resultant liposomal suspensions with the polymer solutions. The circulation and distribution of the liposomes were tested with their intravenous administration in rats. The PVA-R-coated liposomes showed significantly higher circulation compared to that of non-coated ones in any liposomal formulation tested. The prolonged circulation of PVA-R-coated liposomes was attributed to their fewer uptake in liver and spleen. The extent in improvement in the in vivo characteristics were well interpreted by the hydrophobicity of liposomes and their coating amount of PVA-R. It was also demonstrated that the liposomes having a positive and a negative charge, which showed the completely different circulating profiles, showed almost the same profile by coating with PVA-R. When the liposomes were coated with PVA the improvement in blood circulation was much less in any cases, although coating layer of PVA was detected. These results confirm that not only the hydrophilic property but the sterically stabilizing effect of the coating layer is important to prolong the circulation of the particulate drug carriers with less RES uptake, and the PVA-R having a hydrophobic moiety at the end of the molecule of PVA is a suitable material for the coating of liposomes.

Animals↗
PubMed2002

Residual polyvinyl alcohol associated with poly (D,L-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake.

Polyvinyl alcohol (PVA) is the most commonly used emulsifier in the formulation of poly lactide and poly (D,L-lactide-co-glycolide) (PLGA) polymeric nanoparticles. A fraction of PVA remains associated with the nanoparticles despite repeated washing because PVA forms an interconnected network with the polymer at the interface. The objective of this study was to determine the parameters that influence the amount of residual PVA associated with PLGA nanoparticles and its effect on the physical properties and cellular uptake of nanoparticles. Nanoparticles were formulated by a multiple emulsion-solvent evaporation technique using bovine serum albumin (BSA) as a model protein. The parameters that affected the amount of residual PVA include the concentration of PVA and the type of organic solvent used in the emulsion. The residual PVA, in turn, influenced different pharmaceutical properties of nanoparticles such as particle size, zeta potential, polydispersity index, surface hydrophobicity, protein loading and also slightly influenced the in vitro release of the encapsulated protein. Importantly, nanoparticles with higher amount of residual PVA had relatively lower cellular uptake despite their smaller particle size. It is proposed that the lower intracellular uptake of nanoparticles with higher amount of residual PVA could be related to the higher hydrophilicity of the nanoparticle surface. In conclusion, the residual PVA associated with nanoparticles is an important formulation parameter that can be used to modulate the pharmaceutical properties of PLGA nanoparticles.

Biocompatible Materials↗
PubMed1999

Quantitative analysis of polyvinyl alcohol on the surface of poly(D, L-lactide-co-glycolide) microparticles prepared by solvent evaporation method: effect of particle size and PVA concentration.

Polyvinyl alcohol (PVA) is an emulsion stabilizer that is used in the solvent evaporation method for poly(D,L-lactide-co-glycolide) (PLG) microparticles preparation. In this study, the surface binding of PVA on PLG microparticles was quantitatively examined by employing gel permeation chromatography. The PVA binding can affect hydrophobicity and digestibility of the microparticle surface. GPC analysis detected the presence of PVA bound on the microparticle surfaces in an irreversible manner. The PVA content per weight of microparticle increased with the specific surface area as the particle size decreased. The surface PVA density, which is the PVA content per unit surface area of microparticle, changed with particle size in a biphasic manner. In the size range larger than 1 microm, the surface PVA density increased from 0.8 mg/m2 to 2.2 mg/m2 as the particle size decreased. But below 1 microm, the surface PVA density remained unchanged at about 1.8 mg/m2. The surface PVA density of PLG microparticles prepared in different PVA concentrations (0.1, 1, 5, 10% w/v) showed similar values and size dependency, indicating that the PVA concentration of the continuous phase did not affect the surface PVA density of PLG microparticles. These data suggest that the influence of the surface PVA layer would be larger in the smaller particles, but be independent of the PVA concentration of the continuous phase in the manufacturing process.

Adsorption↗
PubMed2003

Review of the oral toxicity of polyvinyl alcohol (PVA).

Polyvinyl alcohols (PVA) (CAS no. 9002-89-5) are synthetic polymers used in a wide range of industrial, commercial, medical and food applications. The purpose of this review, this critical evaluation of the available information on PVA, is to support the safety of PVA as a coating agent for pharmaceutical and dietary supplement products. All the available information on PVA gleaned from a comprehensive search of the scientific literature were critically evaluated. Orally administered PVA is relatively harmless. The safety of PVA is based on the following: (1) the acute oral toxicity of PVA is very low, with LD(50)s in the range of 15-20 g/kg; (2) orally administered PVA is very poorly absorbed from the gastrointestinal tract; (3) PVA does not accumulate in the body when administered orally; (4) PVA is not mutagenic or clastogenic; and (5) NOAELs of orally administered PVA in male and female rats were 5000 mg/kg body weight/day in the 90-day dietary study and 5000 mg/kg body weight/day in the two-generation reproduction study, which was the highest dose tested. A critical evaluation of the existing information on PVA supports its safety for use as a coating agent for pharmaceutical and dietary supplement products.

Administration, Oral↗
PubMed2003

Subchronic toxicity study in rats and genotoxicity tests with polyvinyl alcohol.

The potential systemic and neurotoxicity of polyvinyl alcohol (PVA) was assessed when fed in the diet to male and female Sprague-Dawley rats for 90 days at doses of 2000, 3500 and 5000 mg/kg/day. Control rats received untreated standard laboratory diet. Assessments included clinical observations, ophthalmology, body weight and food consumption, hematology, coagulation, clinical chemistry, urinalyses, motor activity and functional observational battery evaluations and gross and microscopic pathology. The only test-article-related finding observed during the study was unformed stool with brown/black anogenital staining in rats fed 3500 and 5000 mg/kg/day. This finding was attributed to the high levels of test article being consumed and subsequently excreted in the stool. It was not accompanied by macroscopic or microscopic changes in these rats. No test-article-related changes were seen in mortality, ophthalmology, body weight and food consumption data, hematology, clinical chemistry, urinalysis data, functional observational assessments, motor activity, organ weight data and macroscopic and microscopic examinations. Doses of 2000, 3500 and 5000 mg/kg/day of PVA administered as a dietary admixture to male and female Sprague-Dawley rats for up to 90 days did not result in any adverse, toxicological effects. The no-observed-adverse-effect level (NOAEL) was determined to be 5000 mg/kg/day. PVA showed no evidence of mutagenic activity in the Ames test, mouse lymphoma assay and the mouse micronucleus test. (A critical evaluation of the available information on PVA will appear in a review to be published in Food and Chemical Toxicology 2003, 41, 319-326)

Administration, Oral↗
PubMed1998

In vivo percutaneous absorption of [14C]DEHP from [14C]DEHP-plasticized polyvinyl chloride film in male Fischer 344 rats.

These studies investigated the migration of di(2-ethylhexyl) phthalate (DEHP) contained as a plasticizer in polyvinyl chloride (PVC) from plastic film and its absorption through rat skin in iivo. Sheets of PVC film (15 cm2) plasticized with [14C]DEHP were applied to the shaved backs of eight male rats in two separate experiments. For Study I, the PVC film was removed after 24 hr, the animals were rewrapped to prevent them from ingesting any residual DEHP at the exposure site, and urine and faeces were collected at regular intervals for 7 days. For Study II, the PVC film was removed after 24 hr, and the animals were immediately killed by CO2 inhalation. Urine and faeces were collected at 24 hr, and the exposure site was washed and rinsed to remove residual [14C]DEHP. In both studies, the amounts of radioactivity transferred from the film were extremely small, amounting to 0.0643% (Study I) and 0.126% (Study II) of that applied. The transferred radioactivity was found to be in three separate fractions. Radioactivity readily removed from the skin (mean 75% of the transferred radioactivity), radioactivity remaining at the application site at sacrifice. and absorbed radioactivity, that is, that distributed systemically or eliminated. The mean absorption rates for DEHP, calculated from the sum of the quantities absorbed plus that present in the exposure site, were: Study I, 0.239, and Study II, 0.242 microg/cm2/hr.

Animals↗
PubMed2001

Migration of lead from unplasticized polyvinyl chloride pipes.

The effect of water quality parameters, such as water pH, temperature, and total dissolved solids (TDS), and direct exposure to UV-radiation on the migration of lead, tin and other metal stabilizers, such as calcium, cadmium, and barium from unplasticized polyvinyl chloride (uPVC) pipes were investigated using locally manufactured pipes. Specimens of 1m were used to investigate the effect of water quality parameters using the circulatory method. To investigate the effect of UV-radiation, specimens of 33cm long were used throughout the research. The investigation was carried out, using the static method at different times of exposure to the UV-radiation. The concentrations of lead, tin, and other metal stabilizers in the water were evaluated using the inductively coupled argon plasma (ICAP) technique. The results on the effect of water quality parameters showed that water pH, temperature, TDS, and time of water circulation were all having an effect on the migration of lead, tin, and other metal stabilizers. On the other hand, exposure to UV-radiation was seen to promote the migration of lead, tin, and other metal stabilizers. A lead concentration of about 0.8mg/l (ppm) was detected after 14 days of exposure to the UV-radiation.

Hydrogen-Ion Concentration↗
PubMed1997

Polyvinyl alcohol as a defined substitute for serum in vitrification and warming solutions to cryopreserve ovine embryos at different stages of development.

The purpose of this study was to assess the viability of ovine embryos after replacing fetal calf serum (FCS) with polyvinyl alcohol (PVA) in vitrification and warming solutions. Ovine embryos were obtained from superovulated Sardinian breed ewes at 4, 5, 6, and 7 days after insemination. All vitrification and warming solutions were prepared using buffered saline solution with 20% FCS (group a) or 0.1% PVA (group b). Embryos were vitrified in 20 microliters of glycerol 3.4 M + ethylene glycol 4.6 M and loaded into the centre of 0.25 ml straws between two columns of sucrose solution (0.5 M), and plunged immediately into liquid nitrogen. After being warmed in a water bath at 35 degrees C for 10 s, the vitrified embryos were moved to 0.25 M sucrose solution for 3 min. Embryos were cultured in TCM-199 after washing with 10% FCS and sheep oviductal epithelial cells up to hatching or re-expansion of the blastocoelic cavity. No significant difference in the viability rates was observed between embryos vitrified/warmed in PVA or FCS solutions. In both groups, the rate of in vitro viability was (P < 0.01) lower at the precompacted and compacted morula stages than at the expanded, hatching or hatched blastocyst stage. In both groups, early blastocysts were less viable than expanded (P < 0.01), hatching or hatched blastocyst (P < 0.05). There was no significant difference in survival rates at days 14 (79 and 76%) and 45 (63 and 59%) after transfer into sychronised recipients between vitrified expanded blastocysts of groups a and b, respectively. These results suggest that it is possible replace serum with PVA in vitrification and warming solutions without reducing in vivo and in vitro viability.

Animals↗
PubMed2000

Investigation of the release behavior of diethylhexyl phthalate from the polyvinyl-chloride tubing for intravenous administration.

The release behavior of diethylhexyl phthalate (DEHP) from a polyvinyl-chloride (PVC) tube, which is part of an intravenous administration set, was investigated with the coexistence of polysorbate 80 (Tween 80) in various solutions such as physiological saline (PS), distilled water for injection (DWI) and glucose solution (TZ). The cumulative amount of DEHP released after 5 h was in the following order; PS, DWI > 50% TZ. From a comparison of the amount of released DEHP and the critical micelle concentration (CMC) of various solutions, the lower the CMC of the solution, the higher the amount of DEHP released from the PVC tubing. When the concentration of Tween 80 was kept constant at 1 mg/ml, the cumulative amount of DEHP released with a flow rate 90 ml/h was higher than that at 60 ml/h. These results suggest that the release of DEHP from the PVC tubing is closely correlated with the interaction of Tween 80 and DEHP such as the formation of micelles, the collision of micelles against the surface of the PVC tubing and the diffusion properties of DEHP and or Tween 80 in the liquid medium.

Diethylhexyl Phthalate↗
PubMed1999

Interpolymer complexation. I. Preparation and characterization of a polyvinyl acetate phthalate-polyvinylpyrrolidone (PVAP-PVP) complex.

Polyvinyl acetate phthalate (PVAP) and polyvinylpyrrolidone (PVP) readily reacted in ethanol and acidic aqueous solutions to produce an insoluble PVAP-PVP complex. The complex has a pK(a) of 3.8. It is practically insoluble in common organic solvents, but dissolves in dimethylsulfoxide, an alkali or ammonical solution, and a 4:1 (v/v) mixture of methylene chloride and methanol. The powder X-ray diffraction analysis revealed the complex to be an amorphous material. The Fourier-transform infrared spectrum of the complex exhibited characteristics carbonyl stretching vibrations at 1724 and 1657 cm(-1) due to phthalate and acetate moieties in PVAP and cyclic amide groups in PVP, respectively, and at 1632 cm(-1) (appeared as a shoulder) due to cyclic amide groups of PVP bound to PVAP. The proton and carbon-13 (solution and solid-state) nuclear magnetic resonance spectra of the complex showed peak profiles that were linear combinations of those of PVAP and PVP. No new peaks appeared and no change in chemical shifts was observed due to complexation. The spectral data suggest that the interaction between PVAP and PVP probably initially involves the formation of hydrogen bonds between carbonyl groups of PVP and carboxylic groups of PVAP at some point of the polymer chains, causing the hydrophilic parts of the two flexible polymer chains strongly hydrophobic. As a result, the two polymer chains coil up into a compact structure and, consequently, precipitate out from the solution as an insoluble complex.

Chemistry, Pharmaceutical↗
PubMed2001

Determination of polyvinyl alcohol in a poly(DL-lactide-co-glycolide) matrix by size exclusion chromatography using evaporative light scattering detection.

Polyvinyl alcohol (PVA) is used in the manufacture of poly(DL-lactide-co-glycolide) (PLGA) microparticles for the delivery of drugs in an injectable implant form. The levels of residual PVA may affect the release or injectability of the microparticles, and thus must be controlled. Previous work had shown the use of visible detection of iodine-borate complexes of PVA, but this was found to be insensitive and prone to interferences from other formulation components and the sample solvents required. Refractive index detection did not appear to be sensitive enough to detect low levels of PVA. Evaporative light scattering detection was found to be more sensitive and less prone to interferences from the sample matrix than refractive index, and gave reproducible results with acceptable recoveries.

Chromatography, Gel↗
PubMed1999

Stability, compatibility and plasticizer extraction of quinine injection added to infusion solutions and stored in polyvinyl chloride (PVC) containers.

The stability of quinine was determined in various diluents and in polyvinyl chloride (PVC) containers. The release of diethyhexyl phthalate (DEHP) from PVC bags into intravenous infusions of quinine was also measured. We used an injection of two doses of quinine; quiniforme at 500 mg and quinimax at 400 mg in either 250- or 500-ml PVC infusion bags containing 5% dextrose, to give initial nominal concentrations of 2 or 1 mg ml(-1) quiniforme and 1.6 or 0.8 mg ml(-1) quinimax, the mean concentrations commonly used in clinical practice. Samples were assayed by stability-indicating high-performance liquid chromatography (HPLC) and the clarity was determined visually. Experiments were conducted to determine whether the stability and compatibility of quinine would be compromised, and whether DEHP would be leached from PVC bags and PVC administration sets during storage and simulated infusion. There was no substantial loss of quiniforme and quinimax over 1- or 2-h simulated infusion irrespective of the diluent, and storage during 8 h at 22 degrees C, 48 or 72 h at 4 degrees C and 96 h at 45 degrees C. Leaching of DEHP was also detected during simulated infusion delivery using PVC bags and PVC administration sets. The quantity was less than 2 microg ml(-1). During storage at 4 degrees C and room temperature the leaching of DEHP was low, but when the temperature was 45 degrees C the quantity was high, 21 microg ml(-1). To minimise patient exposure to DEHP, quinine solutions with all drugs should be infused immediately or stored for a maximum of 48 h at 4 degrees C.

Antimalarials↗