Biomedical subjects

Y Ikada

Publications and source records attributed to Y Ikada.

At least 235 records · Page 13Linked to original sources

PubMed1991

Water-curable and biodegradable prepolymers.

In an attempt to develop biodegradable polymers which can be shaped in situ and adhere to living tissues, we synthesized esterurethane prepolymers which can be cured upon contact with water in living tissues. First, D,L-lactide polymerization or D,L-lactide-epsilon-caprolactone (50:50) copolymerization was carried out using ethylene glycol or poly(ethylene glycol) as initiator to obtain hydroxyl-terminated biodegradable polyesters. They were then reacted with an excess of diisocyanate such as hexamethylene diisocyanate, toluylene diisocyanate, and diphenylmethane diisocyanate to introduce a reactive isocyanate group to both of the end groups of the polyesters. The isocyanate-terminated prepolymers could be cured in the presence of water and the cured polymers were degraded by hydrolysis both in vitro and in vivo. It was found that the presence of appropriate amounts of hydrophilic units in the main chain was essential for giving a high curing rate and a high degradation rate for the biodegradable urethane prepolymers. The tissue responses to the cured polymers were not severe.

Animals↗

PubMed1991

Covalent immobilization of proteins on to the surface of poly(vinyl alcohol) hydrogel.

Covalent immobilization of cell-adhesive proteins such as collagen and fibronectin on to the surface of poly(vinyl alcohol) hydrogel was investigated by using diisocyanates, polyisocyanates, and cyanogen bromide. It was found that 0.5 and 12 micrograms/cm2 of collagen were immobilized on to the surface by using hexamethylene diisocyanate and cyanogen bromide, respectively. The big difference in the graft amount between the two methods was ascribed to the different reaction media employed for the surface modifications; toluene for the reaction with hexamethylene diisocyanate and water for the reaction with cyanogen bromide.

Collagen↗

PubMed1991

Biodegradation and antitumour effect of adriamycin-containing poly(L-lactic acid) microspheres.

Adriamycin-containing poly (L-lactic acid) microspheres were prepared to develop a slow-releasing and long-acting adriamycin delivery system. An almost constant release of adriamycin from the adriamycin-containing poly(L-lactic acid) was achieved in Tris buffer and adriamycin disappeared within 20 d. Adriamycin was not detected in serum for up to 14 d, when the suspension of the adriamycin-containing poly(L-lactic acid) microspheres was injected into lung parenchyma, the femoral muscles of rabbits or the peritoneal cavity of mice. However, adriamycin remained in the rabbit muscles for up to 10 d under formation of scar tissue. When free adriamycin was added to P815 tumour cells in culture, the cell survival rate decreased with the exposure time. The treatment with the adriamycin-containing poly(L-lactic acid) microspheres showed a higher survival rate for mice bearing P815 tumour cells than with free adriamycin. In addition, the systemic side effects were insignificant when the adriamycin-containing poly(L-lactic acid) microspheres were given to mice instead of free adriamycin.

Animals↗

PubMed1991

Cell behaviour on polymer surfaces grafted with non-ionic and ionic monomers.

Following exposure to corona discharge, a polyethylene film was graft polymerized with different water-soluble monomers such as acrylamide (non-ionic), acrylic acid (anionic), 2-acrylamide-2-methyl propane sulphonic acid (anionic), styrene sulphonic acid sodium salt (anionic) and N,N-dimethylaminopropyl acrylamide (cationic). Attachment and proliferation of HeLa S3 cells were studied for grafted surfaces with different zeta potentials and contact angles. The polyethylene surface graft polymerized with styrene sulphonic acid sodium salt exhibited high cell attachment and protein adsorption, whereas the cells did not adhere to the 2-acrylamide-2-methyl propane sulphonic acid graft-polymerized surface, although both surfaces had high negative zeta potentials. Graft polymerization of acrylamide reduced the zeta potential of surface close to zero and rejected the cell attachment. The polyethylene surface became highly cell-adhesive through graft polymerization of the cationic N,N-dimethylaminopropyl acrylamide monomer, but too much grafting killed the attaching cells. Once the cells attached to a surface without being killed, they could proliferate at the same growth rate, whatever their surface zeta potential.

Acrylic Resins↗

PubMed1991

Low-frictional catheter materials by photo-induced graft polymerization.

To develop low-frictional catheters, photo-induced graft polymerization of N,N-dimethylacrylamide (DMAA) was performed on to films and tubes of ethylene-vinyl acetate copolymer (EVA) and poly(vinyl chloride) (PVC). Their surfaces became very slippery, when the materials were preirradiated with UV from a low-pressure mercury lamp, followed by graft polymerization with DMAA in the presence of small amount of riboflavin without degassing. Although no significant difference was observed in surface lubrication between the EVA film and the tube, the latter required an additional procedure for the graft polymerization, that is, removal of air trapped inside the tube. The surfaces of EVA and PVC tubes grafted with DMAA were found to exhibit frictional forces around 0.5 N against a PVC and a silicone surface under wet conditions, whereas the frictional force of the ungrafted tubes against the same substrates was 10 and 20 N for PVC and EVA, respectively.

Catheterization↗

PubMed1991

In vitro evaluation of sustained drug release from biodegradable elastomer.

Poly(DL-lactic acid) (PLA), poly(epsilon-caprolactone) (PCL), and their copolymers (PLA-CL) with various monomer compositions were synthesized, and their properties as matrix for the sustained release of drugs were evaluated. The copolymerization technique produced very soft films which incorporated the drugs without deterioration of the elastic properties. Cisplatin and MD-805 were loaded in the films by casting the polymer solution containing the drugs. Fractions of the drugs released from the PLA-CL films were governed by the initial loading, the film thickness, and the polymer molecular weight. The drug release profiles obeyed the classical Fickian diffusion equation at least in the early stage, but significant hydrolytic degradation of the matrix polymers occurred in the later stage, influencing the kinetics of drug release. The monomer composition of copolymer affected the release profile more strongly than the initial molecular weight of the copolymer.

Antithrombins↗

PubMed1991

Salt formation of lactic acid oligomers as matrix for sustained release of drugs.

The calcium and sodium salts of L- and D,L-lactic acid oligomers were obtained by immersion of the oligomer powders (weight average mol. wt 3000-10,000) in aqueous solutions of CaCl2 and NaCl, respectively, at room temperature (22 degrees C). The salt formation was analysed by atomic absorption measurement. The thermal properties, including glass transition temperature, melting temperature, and softening temperature, were altered by conversion of the terminal free acid of the oligomer to its salt. An in-vitro release test of an anti-cancer drug from the oligomer beads showed that the drug was released more rapidly from the beads prepared from the non-converted oligomers than those prepared from the salts when the release test was carried out in media containing no calcium and no sodium ions.

Calcium Chloride↗

PubMed1991

A bioabsorbable delivery system for antibiotic treatment of osteomyelitis. The use of lactic acid oligomer as a carrier.

We prepared a composite of D,L-lactic acid oligomer and dideoxykanamycin B for use as a biodegradable antibiotic delivery system with sustained effect. The composite was implanted in the distal portion of the rabbit femur, and the effective concentration of the antibiotic was measured in the cortex, the cancellous bone, and the bone marrow. In all bone tissues around the implant, the concentration of antibiotic exceeded the minimum inhibitory concentration for the common causative organisms of osteomyelitis for six weeks. Most of the implant material had been absorbed and the bone marrow had been repaired to a nearly normal state within nine weeks of implantation. The implant caused no systemic side effects, and it is likely to prove clinically useful as a drug delivery system for treating chronic osteomyelitis.

Absorption↗

PubMed1991

Treatment of malignant pleural effusions with doxorubicin hydrochloride-containing poly(L-lactic acid) microspheres.

For the treatment of malignant pleural effusions, we prepared doxorubicin hydrochloride (Adriamycin)-containing poly(L-lactic acid) microspheres (ADR-MS). In vitro, 50 percent and 100 percent release times of ADR from ADR-MS were 6.3 and 20 days, respectively. After intrapleural administration of ADR-MS for seven patients at an ADR dose of 40 mg, ADR was detected in the effusions for more than two weeks; however, ADR concentrations in serum were very small, consistent with minimal transpleural absorption of ADR. These results indicated the slow release of ADR into the pleural cavity. Furthermore, the amount of drained ADR was less than a few percent of the administered dose. In some cases, malignant cells in the effusion disappeared after the treatment. No complications related to the procedure occurred, and the patients developed no systemic symptoms. One patient died after four months, and the other six patients are alive after 21 to 31 months without reaccumulation of the effusion. The local administration of ADR-MS produces a localized high and systemic low concentration of ADR, which could potentially improve the patient's quality of life.

Aged↗

PubMed1991

Corneal cell adhesion and proliferation on hydrogel sheets bound with cell-adhesive proteins.

The efficiency of protein immobilization to provide a hydrogel surface with a high affinity for corneal epithelial cells was investigated. The cell adhesive proteins collagen and fibronectin, and the cell adhesive oligopeptide RGDS (arginine-glycine-aspartic acid-serine) were successfully covalently immobilized on poly(vinyl alcohol) (PVA) hydrogel sheets. Corneal epithelial cells and L-929 cells were applied to these surfaces. A large number of cells did adhere and proliferate on these protein-bound surfaces in comparison with the virgin PVA not so immobilized.

Amino Acid Sequence↗

PubMed1991

Mechanical effects of a cushioned plate on bone fixation.

In vitro and in vivo experiments were carried out to study mechanical effects of the cushioned plate fixation in which a cushion was placed between a metal plate and bone. The cushioned plate fixation was found to be flexible in the physiological stress range and to reduce the stick slip between bone and the plate. A blood-soaked compression test indicated that the cushion moderates the stress shielding effect which occurs in the vicinity of the rigid plate, this being consistent with the result of in vivo experiments.

Animals↗

PubMed1991

Microspheres of biodegradable polymers as a drug-delivery system in the vitreous.

Microspheres of biodegradable polymers were evaluated as a potential controlled-release drug-delivery system in the vitreous. The microspheres were prepared with polymers of poly(lactic acid) or copolymers of glycolic acid and lactic acid. The release of 5-fluorouracil (5-FU) from the microspheres was studied in vitro. Poly(lactic acid) microspheres released 70-85% of total 5-FU over 7 days. Microspheres of polymers with a smaller molecular weight released the drug more rapidly. Copolymer microspheres released 98% of 5-FU over 2 days. The rate of drug release was controllable by changing the molecular weight of the polymers or using a matrix of copolymer. The intravitreal kinetics of the microspheres were studied in ten rabbits in vivo. A suspension of microspheres was injected into the vitreous cavity of five normal eyes and five vitrectomized eyes. By 48 +/- 5.2 days after injection, the microspheres disappeared from the vitreous cavity in the five normal eyes. Clearance from the vitreous cavity was accelerated in the five rabbits that underwent vitrectomy (14 +/- 2.4 days; P less than 0.001). No difference was found in the b waves of electroretinograms before and after injection of the microspheres. The histologic study showed no abnormal findings as a result of the injection. These results suggested that microspheres of biodegradable polymers may be a potential delivery system for the controlled release of drugs in the vitreous.

Animals↗

PubMed1990

In vivo evaluation of 2-cyanoacrylates as surgical adhesives.

To evaluate 2-cyanoacrylates as surgical adhesives, the bond strength in vivo as well as the tissue reaction was investigated using methyl-, ethyl-, isobutyl-, and ethoxyethyl-2-cyanoacrylate. In addition, their set time and spreading on blood were studied. When the 2-cyanoacrylates were applied to an incised site of rabbit skin, they could maintain the skin closure without suturing during the first week and the bond strength increased during the second week. Significant inflammatory response was observed around the subcutaneous tissue glued with methyl- and ethoxyethyl-2-cyanoacrylate and persisted for approximately one week. All the 2-cyanoacrylate polymers were absorbed and the tissues treated were healed two weeks after the operation. There was a mild inflammatory reaction in the tissue treated with ethyl- and isobutyl-2-cyanoacrylate, and their polymers still remained at the wound site at the second week postoperatively. The disappearance rate of the 2-cyanoacrylate polymers was roughly in proportion to the inflammatory tissue response. Ethoxyethyl-2-cyanoacrylate spread more broadly on tissues than the other 2-cyanoacrylates, while its set time was shorter than that of methyl- and ethyl-2-cyanoacrylates.

Animals↗

PubMed1990

Modified ethoxyethyl cyanoacrylate for therapeutic embolization of arteriovenous malformation.

Aiming at alleviating the problems of using 2-cyanoacrylates as a material for therapeutic embolization, this experiment made some physical modifications by mixing contrast media. It was found that the physicochemical properties of 2-cyanoacrylates can be altered by changing the concentration and the composition of the contrast media added. A 50 wt% cyanoacrylate-50 wt% contrast medium mixture has enough radiopacity for the practical requirement for embolization. A mixture of 50 wt% (ethoxyethyl cyanoacrylate-5 wt% lactide/epsilon-caprolactone copolymer), 25 wt% lipiodol and 25 wt% tetrafluorodibromoethane provides a viscosity of 13.8 cP, a bonding strength of 14.9 kg/cm2, a set time of 6 s, and a spreading in canine blood of 33 mm. It was concluded that the mixture is much more satisfactory than the conventional cyanoacrylates as an embolus material in vitro. The results obtained by in vivo experiments and clinical trials so far suggest that the mixture is very promising as a material for embolization.

Animals↗

PubMed1990

In vitro toxicity test of 2-cyanoacrylate polymers by cell culture method.

The inhibition of Swiss 3T3 cell growth by the microspheres prepared from various 2-cyanoacrylate polymers was investigated to assess their cell toxicity. Poly(ethoxy-ethyl 2-cyanoacrylate) and poly(methyl 2-cyanoacrylate) microspheres inhibited cell growth in a smaller amount than poly-(isobutyl 2-cyanoacrylate) and poly (ethyl 2-cyanoacrylate) microspheres. The extent of cell growth inhibition by the microspheres decreased with the increasing molecular weight, regardless of the kind of polymers used. Every kind of the microspheres was degraded releasing formaldehyde in the culture medium. The cell growth inhibition by the medium containing the microspheres was observed within 24 h for poly(ethoxyethyl 2-cyanoacrylate) and poly(methyl 2-cyanoacrylate). The extent of inhibition was in a linear proportion with the amount of formaldehyde released. It is concluded that the cell toxicity of 2-cyanoacrylate polymers is attributed to formaldehyde released upon polymer degradation.

Animals↗

PubMed1990

Lactic acid oligomer microspheres containing hydrophilic drugs.

A new method was developed for preparation of biodegradable lactic acid oligomer microspheres containing hydrophilic drugs. The microspheres were obtained by removal of solvent from an O/O (oil-in-oil) emulsion through evaporation. The solvent used for the dispersed phase solution was an acetonitrile: water mixture, while the continuous phase medium was cottonseed oil. Doxorubicin hydrochloride (ADR) and insulin were successfully entrapped in the microspheres with high trapping efficiencies of 80 to 90%, and their release profiles were not accompanied with the significant burst effect. The release rate of the drugs from the microspheres was greatly affected by the initial loading of the drugs and the molecular weight of the lactic acid oligomer.

Aclarubicin↗

PubMed1990

Evaluation of polyvinyl alcohol hydrogel as a soft contact lens material.

We prepared a transparent polyvinyl alcohol (PVA) hydrogel from a PVA solution in a mixed solvent consisting of water and a water-miscible organic solvent by cooling. The physical properties of the hydrogel were evaluated in various mixed solvents and compared with those of commercially available soft contact lens materials, such as polyhydroxyethyl methacrylate (PHEMA) and copolymers of methylmethycrylate (MMA) and N-vinyl pyrrolidone (N-VP). The PVA hydrogel showed higher tensile strength and elongation before breaking than did the other materials. Also, the PVA hydrogel was comparable in its high water content and its oxygen permeability with the MMA/VP copolymers. The protein adsorption of the PVA hydrogel was much lower than that of the other materials. Soft contact lenses of PVA hydrogel were applied to rabbit eyes for 12 weeks. The effects of the lenses on the cornea were studied by biomicroscopy, ultrasonic pachymetry, and histopathologic examination. No abnormal findings were noted, suggesting that the PVA hydrogel may be promising as a new material for use in soft contact lenses.

Animals↗

PubMed1990

Clinical evaluation of a new bilayer "artificial skin" composed of collagen sponge and silicone layer.

A bilayer "artificial skin" composed of an outer layer of silicone and an inner sponge layer of collagen and chondroitin sulphate has been developed by modifying the technique proposed by Yannas et al. (1980). Following experimental successes, the "artificial skin" was applied clinically. It was placed on the skin defects of 10 patients. Three weeks after application the outer layer of silicone sheet was peeled off and thin split thickness skin was grafted onto the newly synthesised dermis-like tissue. Secondary skin grafts took perfectly in all cases and postoperative appearance was satisfactory.

Adolescent↗