Kouichi Sutani

Stimulus responsive drug release from polymer gel.: Controlled release of ionic drug from polyampholyte gel

Abstract 2-(Dimethylamino)ethyl methacrylate or Methacryloyloxyethyltrimethylammonium chloride as a cationic monomer was copolymerized by UV with anionic monomer such as acrylic acid (AAc), into a polyampholyte. The pH responsive swelling behaviour and the pH and electro-responsive drug release functions of polyampholyte were investigated. The result showed that a copolymer of cation rich composition swelled at acidic condition, and shrank at alkaline condition. On the other hand, an anion rich copolymer showed a reverse phenomenon. Polyampholyte proved to interact with an ionic drug both by ionic binding and physical adsorption.

The synthesis and the electric-responsiveness of hydrogels entrapping natural polyelectrolyte

Abstract A mixture of vinyl monomer, a natural polyelectrolyte—hyaluronic acid—and crosslinker was polymerized and crosslinked to entrap the natural polymer into the synthetic gel. The controlled release of the model drug from the obtained gel was studied under the on–off switching of electric field. It was proved that electric-responsive drug releases were possible using hyaluronic acid entrapping gel and the electro-responsiveness was greatly affected by various factors such as degree of swelling, crosslinking density, kind and composition of vinyl monomer and crosslinkers.

Intelligent biomembrane obtained by irradiation techniques

Abstract An intelligent biomembrane for environment-responsive feedback releases has been developed using radiation techniques. Various fine-porous base membranes (polyester, polycarbonate, silicon) were prepared by hole fabrication techniques with excimer-laser, ion-beam etching and photo-lithography etching. Then, various monomeric mixture of stimuli-sensitive hydrogels with or without immobilized enzymes were coated and polymerized on the porous membrane by UV, γ -ray or electron beam. The product showed the intelligent feedback release functions of model substance (methylene blue) in response to the on–off switching of signals such as pH changes and introduction of electric field. The responsiveness was remarkably improved by radiation induced IPN (interpenetrating polymer network) formation. Intelligent release controlled by a computer program was also studied and proved.

Intelligent type controlled release systems by radiation techniques

Intelligent controlled release systems have been designed and constructed. The systems have a sensor-actuator gate consisting of polyelectrolyte hydrogel layer with immobilized enzymes inside fine holes of polyethylene terephthalate (PET) film and silicon wafer as base materials. Excimer-laser or ion-beam irradiation was used for the etching of holes in PET film and photo-lithography was used for the etching of silicon wafer. U.V. and γ-ray irradiations were used for the polymerization and immobilization of electrolyte layers in the holes. Various kinds of signal responsive release systems such as pH responsive, substrate responsive, Ca2+ responsive, photo-responsive and electric field responsive systems have been developed using those techniques. Some integrated systems have been designed and constructed by combination of unit systems in series and in parallel and proved the selective signal transfer and the successive signal responsive release functions.

Temperature and pH responsiveness of poly-(DMAA-co-unsaturated carboxylic acid) hydrogels synthesized by UV-irradiation

Abstract Stimuli-responsive polyampholyte hydrogels were synthesized by the copolymerization of dimethylaminoethyl methacrylate (DMAA) and acrylic acid (AAc) or itaconic acid (IAc) by UV-irradiation. Temperature and pH responsiveness of these hydrogels were studied. The temperature responsiveness of poly-(DMAA-co-AAc, IAc) hydrogels shown in change of water content became dull compared to that of DMAA homo-polymer hydrogel. The water content of the poly-(DMAA-co-AAc, IAc) hydrogels showed a minimum at pH 8, and increased in more acidic and alkaline regions. This fact can be attributed to the coexistence of anions and cations in the poly-(DMAA-co-AAc, IAc) hydrogels. The poly-(DMAA-co-AAc, IAc) hydrogels were polyampholyte having both temperature responsiveness and pH responsiveness.

Radiation curing of intelligent coating on biofunctional membranes

Abstract Intelligent membranes for the controlled permeation and release of drugs were prepared by coating and curing process of mixture consisting of electrolyte monomer and UV curable monomer on a porous polymeric film or a drug-containing film. pH- and substrate responsive drug permeation and controlled releases could be attained effectively using those intelligent membranes.

Intelligent feedback release systems and the application to neuron network model research

Abstract Intelligent feedback release systems, consisting of radiation-prepared porous polycarbonate film or silicone chip and radiation crosslinked stimuli-sensitive hydrogels with immobilized enzymes as a sensor–actuator gate were constructed. Those systems showed various signal responsive substance release functions, and selective signal transfer functions. The application of those integrated intelligent systems as neural network model was investigated.

The preparation of the chronic hyper-endotoxemia experimental animal model by means of a drug delivery system.

A drug delivery system (DDS) consisting of lipopolysaccharide (LPS) as a drug and 2-hydroxyethyl methacrylate (HEMA)-diethylene glycol dimethacrylate (2G) or -polyethylene glycol dimethacrylate (4G, 9G) copolymer was prepared, and used for the efficient preparation of an experimental animal model of chronic hyper-endotoxemia. The release profiles of LPS in the in-vitro test were greatly influenced by the composition of HEMA-2G, 4G, 9G in the copolymer. It was found that LPS release from the DDS continued gradually and constantly throughout 2 weeks. In the in-vivo experiment with rats, the DDS maintained a high blood concentration level of LPS for 3 days. These results strongly suggest the possibility of convenient and reproducible preparation of a chronic hyper-endotoxemia animal model.

PREPARATION OF HYALURONAN GEL AND THE APPLICATION TO DRUG DELIVERY

ABSTRACT The stable gelation of hyaluronic acid by entrapping with other networked polymers was investigated. One method is the entrapping polymerization with hydrophilic vinyl monomers such as hydroxyethyl methacrylate and acrylamide. The other is the entrapping with natural polymers such as agarose. Both methods gave the stable hydrogel products. Some model drugs were added to a hyaluronan solution and included into the gel by entrapping. The hyaluronan gel showed an intelligent function, showing reverse volume changes (shrinkage and expansion) with the on-off switching of signal input. Intelligent controlled release of model drugs in response to the changes of environmental conditions such as pH changes and on-off switching of electrical field was also studied. Those results suggested hyaluronan entrapped hydrogel acts as a polyelectrolyte.

Electro-responsive on-off switching controlled release systems using solenoid as an actuator.

Electro-responsive on-off switching controlled release devices using solenoid for the actuator were prepared and the functions were tested. The devices were constructed from solenoid, bias spring and drug reservoir with an iron plate in a wan and a hole gate in the bottom. It was found that the drug reservoir moved by magnetic interaction according to input of electric current through the solenoid so as to fit the gate holes to cause the drug release from the reservoir. Then, the effects of magnetic flux density, moved distance of reservoir and number of nichrom wire coil on the on-off switching function were examined. The competent and compactness of solenoid were also improved. U shape solenoid and permalloy for solenoid core was used to increase the megnetic power. It was proved that on-off switching release of methylene blue as a model drug occurred quickly and sensitively with on-off switching of electromagnetic field in the device using the solenoid as the actuator.