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N-Isopropylacrylamide
Impregnation of polymers with drugs for medicinal purposes seems to be the most popular use of ScF technologies. I was asked to investigate NIPA (N-isopropylacrylamide) and its possible applications. NIPA is an “intelligent material” which is a thermosensitive polymer having a lower critical solution temperature of around 32°C. Below LCST, NIPA is water soluble and above LCST NIPA is water-insoluble. NIPA gel is transparent in water and swollen at room temperature. The volume change as it passes through LCST is about 20%. The volume change can last a long time. Another curious attribute is that below LCST NIPA is transparent, but above LCST NIPA becomes opaque. This change is instantaneous. These properties are allowing researchers to look into applications of optical switches, Braille touch tablets for the blind, Polymer Gel based actuators, drug delivery systems, tissue engineering scaffolds and photolithographic technique produced micro-patterns.
7.1 Intelligent Gels
In 1975 Toyoichi Tanaka of MIT (Massachusetts Institute of Technology) discovered that by cooling a clear polyacrylamide gel, they could make it cloud up and eventually become opaque. He also discovered that a small change in solvent concentration or temperature can cause a gel to abruptly swell to many times its original size or collapse into a compact mass.
Such a definitive phase transition had not been seen before in synthetic polymers, although it had been predicted in 1968. Certainly, gels that swell or contract gradually over time had been known for more than 25 years before Tanaka began his experiments. But his gels were different--they reacted to an external stimulus in a manner more reminiscent of living organisms than inanimate matter.
In 1992, recognizing that responsive-gel technology was ripe for commercialization, Tanaka and entrepreneur George W. McKinney III founded Gel Sciences in Bedford, Mass., to pursue industrial applications of the technology. The company commercialized its first product: a viscoelastic gel that is soft and pliable at room temperature but becomes much firmer when exposed to body heat. The material, dubbed SmartGel, is being used as a shoe insert--for instance, in in-line skate shoes--to make the shoe conform to the wearer's foot and provide the necessary support and comfort.
Gel Sciences/GelMed has had its disappointments too, but it is determined that SmartGel will not be its only success story. A similar product, trade named Smart Hydrogel, is currently being developed for drug delivery and skin care applications. Not only does Smart Hydrogel respond to temperature, it adheres to biological tissue and is sensitive to shear forces. That makes it a promising matrix material for longer lasting eye drops, nasal sprays, and sunscreens, says Ron.
Conventional eye drops are quickly diluted and washed away by tears. Although Smart Hydrogel is dropped onto the eye as a liquid, it responds to the higher temperature of the eye by becoming more viscous. Furthermore, because of its sensitivity to shear, the gel momentarily becomes liquid every time the eye blinks, allowing the gel to be spread evenly over the entire eye. The gel can thus slowly release medication to the eye over the course of hours, not minutes. Similar benefits accrue when the gel is used for nasal sprays. Nasal delivery of drugs such as insulin could replace injection, which is more difficult for patients to do themselves. According to Ron, Gel Sciences/GelMed is interested in using Smart Hydrogel to deliver, for instance, antiglaucoma and anti-inflammatory drugs to the eye and decongestants and hormones to the nose.
Sunscreens and other skin care products also could benefit from the unique properties of Smart Hydrogel. One problem with ordinary sunscreen lotions is that they are oily and the active ingredient penetrates the skin and enters the bloodstream, where it is no longer effective, Ron explains. Smart Hydrogel is water based and encases the sun-blocking agent in micelles, keeping it on the skin longer.
Drug delivery is not the only hydrogel application that stands to benefit from the biomimetic approach. MIT's Tanaka believes that synthetic polymers, if properly designed, can do what proteins do: recognize a specific molecule, capture it, then release it when appropriate. For example, hemoglobin reversibly binds to molecular oxygen and ferries it from the lungs to oxygen-starved cells.
The expansion and contraction of gels allow chemical or electrical energy to be converted into mechanical work. Because of this phenomenon, gels have long been viewed by scientists as a potential material for artificial muscle, for use in robotic actuators or prosthetic limbs. In 1991, David L. Brock, a researcher in MIT's Artificial Intelligence Laboratory, wrote in an internal document that recent research in polymer gels" offers the hope for an artificial muscle and a potential revolution in robot actuator design." But he also noted that many fundamental physical and engineering hurdles remain to be surmounted in this quest.
Researchers also have made progress in speeding up the response time of contractile gels, which were exceedingly slow in the beginning. But response time is still not fast enough, notes Gel Sciences' Ron, and gels for artificial muscle are "still far away from commercial reality."
But perhaps researchers at Rensselaer Polytechnic Institute in Troy, N.Y., have the answer. RPI chemistry professor Sonja Krause and doctoral student Katherine Bohon have created a gel that can respond to an electric impulse in 100 milliseconds. That's how long it takes human skeletal muscles to contract after they receive an electrical signal from the brain.
In preliminary "feasibility" experiments, Bohon used commercially available materials. She made a gel by infusing an elastic poly(dimethylsiloxane) with an electrorheological fluid, a suspension of cross-linked poly(ethylene oxide) particles in silicone oil containing salt and other additives. When an electric field is applied to the fluid, it becomes a stiff, elastic solid in about 1 millisecond. Bohon embedded two flexible electrodes in the gel and applied a 1-Hz ac electric field to it, watching it compress in less than 100 milliseconds and then stretch when the current reversed. Tiny flags she had glued to the electrodes made it easy to see the two pulsations per second.
While most intelligent gels are designed to respond to external stimuli, a research team in Japan has engineered a gel that responds to an internal stimulus. And since that internal stimulus oscillates between two states, the gel alternately expands and contracts, creating "dynamic rhythms as if it were alive," according to Ryo Yoshida, Toshikazu Takahashi, Tomohiko Yamaguchi, and Hisao Ichijo of the National Institute of Materials & Chemical Research in Tsukuba [Adv. Mater., 9, 175 (1997)].
Some scientists have suggested that smart gels could form the basis of a future "soft, wet" technology that might one day replace certain aspects of today's technology, which is based on metals and other hard materials. The automaker Toyota is said to have looked into the possibility that soft, responsive systems could replace hard materials.
Spec Sheet for NIPA and CAS number
http://ull.chemistry.uakron.edu/erd/chemicals1/11/10325.html
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