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Polymers that display a physicochemical response to stimuli are widely explored as potential drug-delivery systems1,2,3,4. Stimuli studied to date include chemical substances and changes in
temperature, pH and electric field. Homopolymers or copolymers of N-isopropylacrylamide5,6 and poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (known as poloxamers)7 are
typical examples of thermosensitive polymers, but their use in drug delivery is problematic because they are toxic and non-biodegradable. Biodegradable polymers used for drug delivery to
date have mostly been in the form of injectable microspheres or implant systems, which require complicated fabrication processes using organic solvents8. Such systems have the disadvantage
that the use of organic solvents can cause denaturation when protein drugs are to be encapsulated. Furthermore, the solid form requires surgical insertion, which often results in tissue
irritation and damage. Here we report the synthesis of a thermosensitive, biodegradable hydrogel consisting of blocks of poly(ethylene oxide) and poly(L-lactic acid). Aqueous solutions of
these copolymers exhibit temperature-dependent reversible gel–sol transitions. The hydrogel can be loaded with bioactive molecules in an aqueous phase at an elevated temperature (around 45
°C), where they form a sol. In this form, the polymer is injectable. On subcutaneous injection and subsequent rapid cooling to body temperature, the loaded copolymer forms a gel that can act
as a sustained-release matrix for drugs.
We thank to G. G. Krueger for comments on dermatological issues and J. S. Kim for technical assistance. D. S. Lee was supported by the Ministry of Education of Korea. This work was supported
by the University of Utah Research Foundation.
Biomedical Polymers Research Building, Room 205, CCCD/Pharmaceutics, University of Utah, Salt Lake City, UT 84112, USA
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