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.
We reported aqueous solutions of poly(caprolactone-b-ethylene glycol-b-caprolactone) (PCL−PEG−PCL) that underwent sol−gel−sol transition as the temperature increased (Macromolecules 2005, 38, 5260−5265). However, when the triblock copolymer aqueous solution (20 wt %), initially as a sol phase, was left at room temperature (20 °C), it turned into an opaque gel in 1 h. The crystallization of the PCL−PEG−PCL triblock copolymer in water was suggested to be responsible for such a kinetic aspect of the phase transition. In addition, PEG/PCL multiblock copolymers were synthesized by coupling the triblock copolymers using terephthaloyl chloride. Even though both PCL−PEG−PCL triblock and PEG/PCL multiblock copolymer aqueous solutions (20 wt %) instantaneously undergo a sol-to-gel transition upon injection into 37 °C water and their thermogels show a maximum modulus at around body temperature (35−42 °C), the multiblock copolymer shows a pronounced sol phase stability at room temperature. The fundamental difference in such phase behavior between triblock and multiblock copolymers seems to lie in their ability to form micelles at low temperature and high crystallizability of the low molecular weight PCL.
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...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.