Poly(caprolactone-b-ethylene glycol-b-caprolactone) (PCL-PEG-PCL) triblock copolymer aqueous solution (>15 wt %) undergoes the sol-gel-sol transition as the temperature increases from 10 to 60 °C. The mechanism and structure-property relationship of the sol-gel transition were investigated. In particular, compared with the PEG-PCL-PEG triblock copolymers recently reported by our group, PCL-PEG-PCL has (1) a synthetic advantage without a hexamethylene diisocyanate coupling step, (2) a wider gel window of over 15-32 wt %, and (3) a larger gel modulus. Both PEG-PCL-PEG and PCL-PEG-PCL polymers are an important progress in the biodegradable thermogelling system in that they can be lyophilized in a powder form, are easy to handle, are easy to redissolve to a clear solution, and show little syneresis through the gel phase.

The aqueous solution of poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) triblock copolymers (> 15. wt. %) undergoing "clear sol-gel-turbid sol" transition as the temperature increases from 20 to 60 degrees C has been developed. Light scattering and 13C NMR study suggested that the transition mechanisms are the micellar aggregation for the clear sol to gel transition (lower transition), whereas the increase in PCL molecular motion for gel to turbid sol transition (upper transition). In contrast to the previous thermogelling biodegradable polymers with a sticky paste morphology, the powder form of the PEG-PCL-PEG triblock copolymers makes it easy to handle and allows fast dissolution in water. Therefore, the lyophilization into a powder form followed by facile reconstitution was possible. This system is believed to be promising for drug delivery, cell therapy, and tissue engineering.

The thermogelling properties of aqueous polymer solutions have been hot topics of research due to their potential biomedical applications as well as to interest in understanding sol±gel transition mechanisms.[1] In particular, poloxamer, a triblock copolymer of poly(ethylene glycol)±poly(propylene glycol)±poly(ethylene glycol), and its derivatives, such as poloxamer-g-poly(acrylic acid) (Smart Gel), 3,4-dihydroxyphenylalanine (DOPA)-conjugated poloxamers, and biodegradable multiblock poloxamers, have been investigated.[2]Aqueous solutions of the above polymers are free-flowing sols at low temperature, whereas they turn into gels at physiological temperature by a heat-induced sol-to-gel transition. Therefore, aqueous polymer solutions containing drugs or cells have been proposed as injectable reservoir systems.[3] However, small-tissue adhesion and blockage of a long needle, especially a catheter, by gelation during injection of the formulation of the drug or cell limits their application. In addition, the pH in our body varies from 1±8 depending on the site as well as pathological condition. For example, vaginal pH is 3.7±5.5 and tumoral pH is~5.7±7.4. [4,5] Considering the above facts, we designed a multiblock poloxamer (MBP) with carboxylic acids and investigated the gelation characteristics as a function of pH and temperature. The synthetic route (Scheme 1) of the MBP shows that two moles of carboxylic acid groups are generated by one mole of terephthalic anhydride in the coupling reaction.Dynamic rheological analysis showed that the MBP aqueous solution (30 wt.-%) did not undergo appreciable change in dynamic viscosity (g¢) as the temperature was increased to 45 C at pH 7.4, indicating that the sol-to-gel transition did not occur. The increased hydrophilicity of the ionized carboxylic acid groups solubilize the MBP at pH 7.4. To see the effect of pH change on gelation, the viscosity of MBP (30 wt.-%) was measured as a function of pH and temperature (Fig. 1). The abrupt increase in viscosity at 25±30 C indicates the sol-to-gel transition of the MBP aqueous solution in a pH range of 4±6. Interestingly, the gel phase is observed in a specific pH range of 4±6 at 37 C. At low pH (< 3) and high pH (> 7.4), an appreciable increase in viscosity, that is, a solto-gel transition, was not observed.pH-and temperature-sensitive polymers such as poly(N-isopropylacrylamide-co-acrylic acid); poly(styrene-co-maleic anhydride) (SMA) grafted to poly(ethylene glycol) (PEG) (SMAg-PEG); and poly(N-vinylcaprolactam-co-methacrylic acid) have been reported.[6±8] They form gels at low pH and high temperature. However, there is no report of a polymer with a closed-loop gel phase, where the gel exists at a certain pH range and becomes a sol phase in both low-and high-pH regions.To get some idea of the closed-loop pH-dependent behavior, we hypothesized two opposing forces. First, as the pH increases, carboxylic acid (±COOH) is ionized to its conjugate carboxylate anion (±COO ± ), which increases the hydrophilicity of the MBP and makes th...

Biodegradable multiblock poloxamers (BMPs) with gel duration of 8 h to several weeks were prepared by varying their molecular weights from 4000 to 40 000 g mol−1. The molecular weight of the BMP was controlled by changing the poloxamer to coupling agent ratio. Assuming a micelle packing model of the BMP gel, as in the case of a poloxamer gel, the micelle properties and critical gel concentration of BMPs were investigated on the basis of the scaling concept. The findings suggest that the control of molecular weight by hydrolyzable groups can be a facile approach to optimize the gel properties for biomedical applications. Copyright © 2005 Society of Chemical Industry