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Biomedical subjects

K Sugibayashi

Publications and source records attributed to K Sugibayashi.

At least 91 records · Page 5Linked to original sources
PubMed1985

Influence of 1-dodecylazacycloheptan-2-one (Azone) on the topical therapy of cutaneous herpes simplex virus type 1 infection in hairless mice with 2',3'-di-O-acetyl-9-beta-D-arabinofuranosyladenine and 5'-O-valeryl-9-beta-D-arabinofuranosyladenine.

The predictive value of a recently developed physical model was tested in the topical treatment of cutaneous infections caused by herpes simplex virus type 1 in hairless mice with two ester prodrugs of 9-beta-D-arabinofuranosyladenine (ara-A) (1). The tests were conducted with 2',3'-di-O-acetyl-ara-A (4) and 5'-O-valeryl-ara-A (3) topically applied with and without 15% 1-dodecylazacycloheptan-2-one (2) (Azone), a percutaneous penetration enhancer. In addition to the in vivo studies, in vitro diffusion cell experiments with excised, full-thickness skin from hairless mice were conducted to determine the penetration enhancement effects of 2. As previously observed, 2 was able to induce remarkably large (100- to 1000-fold) flux enhancements in these in vitro experiments. Consistent with predictions based on the physical model studies, formulations of 3 and 4 without 2 had little or no influence on the pathogenesis of the herpes simplex virus type 1 infections; when 2 was present in the formulations, both 3 and 4 had dramatic therapeutic effects consistent with the predictions made with the physical model. Prodrug 4 with 2 was especially efficacious in the prevention of virus-induced lesions and in the survival of all animals. Similar results were obtained with acyclovir plus 2 in this model system.

Acyclovir↗
PubMed1985

Mitomycin C carrying microspheres as a novel method of drug delivery.

Biodegradable albumin microspheres containing about 5% mitomycin C (MMC) were prepared in an average diameter of 45 +/- 8 microns by heat denaturation in oil at 120 degrees C and/or cross-linking with glutaraldehyde. These MMC microspheres released, in vitro, about 20% of the contained MMC for over 3 days, and they were intra-arterially infused into albino rabbits and Wistar rats, as a preclinical model of intra-arterial infusion treatment for patients with inoperable hepatic tumor. We infused these microspheres into the femoral artery of rabbits with a VX-2 tumor implanted into the flank of the hindleg. High levels of MMC were maintained for several hours in the tumor and the entrapped MMC microspheres were detected within arterioles in the VX-2 tumors. The growth of VX-2 tumor was inhibited considerably, compared to findings in the control rabbits given conventional MMC. In the next studies, MMC microspheres were infused into the rat hepatic artery, and the levels of MMC in the hepatic vein blood were maintained at much the same concentration for over 2 hours after the infusion, in marked contrast to rapid decreases in the conventional MMC. Histologic findings revealed that MMC micro-spheres were entrapped within the hepatic arterioles for over 2 weeks and released biologically active MMC into the neighboring tissues for prolonged periods of time.

Albumins↗
PubMed1985

Effect of the absorption enhancer, Azone, on the transport of 5-fluorouracil across hairless rat skin.

The effect of the percutaneous absorption enhancer, Azone, on the transport of 5-fluorouracil across hairless rat skin has been investigated by an in-vitro permeation technique using 2-chamber diffusion cells. Azone (3% w/v) emulsions were used. Azone enhanced the permeability of drug 10-100 times across the full-thickness skin although there was a lag time about 10 h. The long lag time, however, disappeared with Azone pretreatment. Azone also affected the transport across stripped skin. These results suggest that Azone mainly affects the stratum corneum. It seems to change the diffusivity of drug in that layer and is not so effective against diffusivities in the epidermis and dermis.

Animals↗
PubMed1984

Effect of azone and propylene glycol on penetration of trifluorothymidine through skin and efficacy of different topical formulations against cutaneous herpes simplex virus infections in guinea pigs.

Tropical formulations of 5-trifluoromethyl-2'-deoxyuridine (TFT) containing different concentrations of TFT, Azone (Nelson Research and Development, Irvine, Calif.), and propylene glycol were evaluated for their potential efficacy in the treatment of cutaneous herpes simplex virus infections by in vitro studies of TFT penetration through skin and in vivo studies of therapeutic activity against herpes simplex virus type 1 infections in the dorsal cutaneous guinea pig model. Azone dramatically increased TFT penetration through human and guinea pig skin. Unexpectedly, high concentrations of propylene glycol were also associated with increased penetration. Studies in the guinea pig model revealed increased efficacy with Azone-propylene glycol-containing formulations, consistent with the in vitro drug diffusion results. A formulation containing 1% TFT, 5% Azone, and 80% propylene glycol decreased lesion area, in comparison to the drug vehicle control, more effectively than 5% acyclovir in polyethylene glycol (reduction of 70 versus 46%, P = 0.03). These studies demonstrate the value of penetration-enhancing agents and the need for careful preclinical evaluations in the development of topical antiviral agents.

Administration, Topical↗
PubMed1984

Antitumor agent poly (amino acid) conjugates as a drug carrier in cancer chemotherapy.

Antitumor agent melphalan was conjugated through a carbodiimide-catalyzed reaction to poly (L-lysine) (71.3K and 2K) and poly (L-glutamic acid) (60K and 14K) at a ratio of approximately one molecule per 7-lysyl and 23-glutamate residues, respectively. These conjugates had 40-70% of alkylating activities by themselves in vitro as compared with free melphalan. Poly (glutamic acid) conjugates showed the antitumor activity in vivo against Yoshida sarcoma in rats. In addition, poly (glutamic acid) conjugates containing 3H-phenylalanine which was used as a model compound instead of melphalan had a sustained release property of radioactivity and the release rates could be regulated by exopeptidases. After subcutaneous injection as the first choice of routes of administration, moreover, the conjugates were found to be absorbed through the lymphatic transport system, probably due to the macromolecularity. These results suggest that the melphalan-poly (amino acid) conjugates are one of good candidates to attain the sustained release and targeting of drugs in cancer chemotherapy.

Absorption↗
PubMed1983

Continued in vitro and in vivo release of an antitumor drug from albumin microspheres.

Heated albumin microspheres with an average diameter of 45 +/- 8 microns and containing mitomycin C, released, in vitro, about 20% of this antibiotic over a 3-day period. VX-2 tumors were implanted into the hind leg of rabbits and the drug-containing microspheres were injected into the femoral artery of these animals. High levels of the drug were maintained for several hours in the tumor and growth of the tumor was inhibited considerably, compared to findings in control rabbits given the conventional mitomycin C. Half the number of the rabbits treated with our new method are alive with no evidence of tumor.

Animals↗
PubMed1983

[Studies on biodegradable microspheres containing mitomycin C].

For the purpose of enhancing antitumor effects, we prepared heated albumin microspheres containing an antitumor drug, mitomycin C. The biodegradable MMC microspheres which have an average diameter of 45 +/- 8 mum contain approximately 10% of MMC and release in vitro approximately 20% of the MMC over 3-day period. The microspheres were injected into albino rabbit femoral artery of the hind leg into which a VX-2 tumor had been implanted. Peripheral blood levels of MMC were reduced as compared to the conventional MMC group, within 60 minutes after injection. Subsequently in the MMC-microsphere administered rabbits, the level was higher than in the conventional MMC administered group. The survival of VX-2 tumor-bearing rabbits prolonged markedly with MMC microspheres.

Animals↗
PubMed1981

Biomedical applications of magnetic fluids II. 1) preparation and magnetic guidance of magnetic albumin microsphere for site specific drug delivery in vivo.

Magnetic guidance of magnetic albumin microsphere for site specific delivery was investigated in mice and rats. After intravenous injection in mice, magnetic microspheres with 1 and 3 micrometer diameter size were localized and retained in the target-site (lung) by application of two permanent magnets to the lungs. Injection into the renal artery in rats also indicated that the 1-micrometer microspheres were concentrated in the kidney by a magnetic field. When the magnets were not applied, however, the microspheres following intravascular injection were concentrated mainly in the liver, regardless of the route of administration. Such preferential localization by magnetic means suggested that magnetic albumin microspheres could become effective drug carriers with site specificity for the delivery of chemotherapeutic agents in cancer therapy.

Animals↗
PubMed1981

Spectrophotometric analysis for fluorouracil in biological fluids.

Fluorouracil (5-fluorouracil; 5-FU) is a monoanion at pH = 10 and forms an ion-pair complex with a quaternary alkylammonium ion. De Leenheer and co-workers [2] reported that the ion-pair complexes might be quantitatively extracted from aqueous solutions into organic solvents, and they spectrophotometrically determined the concentration of 5-FU. But as their method used column chromatography, it was cumbersome and time-consuming. Here we present a more rapid chemical assay of 5-FU by modifying the principle of their method. The applicability of this method was shown by determining the plasma and tissue levels of 5-FU in mice.

Animals↗
PubMed1980

Biomedical applications of magnetic fluids. i. Magnetic guidance of ferro-colloid-entrapped albumin microsphere for site specific drug delivery in vivo.

Magnetic guidance of magnetic albumin microsphere for site specific drug delivery was investigated in vivo. After intravenous injection in mice, magnetic microspheres localized in the site (lung) at which two permanent magnets were placed. Injection into the renal artery in rats also indicated that the microspheres were concentrated at the kidney by a magnetic field. When magnet was not applied, however, the microspheres were concentrated mainly in the liver. Such preferential localization by magnetic means suggested that magnetic albumin microspheres could become effective drug carriers with site specificity for the delivery of chemotherapeutic agents in cancer therapy.

Albumins↗