Hiroshi Tanzawa

Ocular inserts for controlled release of antibiotics

Ocular inserts impregnated with antibiotics (erythromycin and erythromycin estolate) which have sustained release characteristics were prepared, mainly for the purpose of trachoma therapy. In vitro experiments showed that the elution rate of a drug with low solubility in water (erythromycin estolate) is constant when the water content of the hydrogel insert is more than 30%. In the case of a drug with higher solubility (erythromycin), the elution rate depends on the water content. Some in vivo experiments using rabbit eyes were also reported.

Cell proliferation on hydrogels

SummaryThe adhesion and proliferation of mammalian fibroblasts (Flow 7000) on the surface of hydrophilic (copolymer ofN-vinyl-2-pyrrolidone and methyl methacrylate) and hydrophobic [polymethylmethacrylate (PMMA) stereocomplex] hydrogels with a wide range in water content were studied morphologically and quantitatively. It was demonstrated that cell proliferation on hydrogels by a static culture method decreased as the water content of the gels increased. However, it is remarkable that the cell proliferation on PMMA hydrogels with a high water content is equivalent to that on glass Petri dishes. The results obtained in the proliferation of cells on the surface of these hydrogels closely correspond to the state of cell adhesion. When fresh medium or air was perfused from the popposite side of the PMMA hydrogel membrane on which the cells were proliferating (perfusion method), the cells continued to grow into a higher density than with the conventional static culture method. In the case of fresh medium perfusion, the amount of proliferated cell was dependent on both the permeability of the membrane and the density of the membrane “scaffolding”. Virus multiplication in the cultured cells increased in proportion to the cell density, whereas the cell function was similar in both culture methods.

In vivo evaluation of ocular inserts of hydrogel impregnated with antibiotics fop trachoma therapy

Sustained release of antibiotics from hydrogel matrices in the eye was studied for the purpose of developing a new method for trachoma therapy. Copolymers of N-vinylpyrrolidone were moulded into an ocular insert and impregnated with erythromycin or erythromycin estolate. The antibiotic-hydrogel inserts completely suppressed the chlamydia trachomatis infection in the owl monkey eyes. The drug elution rates were a little lower in vivo than in vitro. By comparison of the drug elution rate in the human eye with that in the owl monkey eye, similar therapeutic effect is expected in the treatment of human trachoma.

Formation of Poly(Methyl Methacrylate) Membranes Utilizing Stereocomplex Phenomenon

Sheet1) and hollow fiber membranes with stabilized porous structure were formed from poly(methyl methacrylate) (PMMA) by making use of stereocomplex phenomenon, which occures in the mixture solution of isotactic and syndiotactic PMMA, and which is a stoichiometric and thermoreversible sol-gel phase transition phenomenon.2)–5) This report will show the formation processes, permeability characteristics, and medical applications of PMMA membranes.

The Application of Luminol-Bound Microspheres for the Quantitative Analysis of Toxic Oxygen within Phagosomes

Hydrophilic microspheres, with a diameter of about 2μm, composed of glyceryl methacrylate and methacrylic acid were prepared. The microspheres could be stably stored in dispersed state and demonstrated little non-specific adherance to cell membranes. Luminol-bound microspheres, prepared by covalently binding luminol to microspheres, were phagocytosed by phagocytic cells without opsonization. Luminol bound to the microspheres was oxidized by toxic oxygen within phagosomes resulting in the generation of chem iluminescence. The chemiluminescence elicited by luminol-bound micro spheres was an effective method of measuring the candidacidal activity of the cells. The difference in phagosomal toxic oxygen versus extracellular toxic oxy gen was examined.