Gelation behavior of PEO±PLGA±PEO triblock copolymers in water Kwan-Wook Kwon a , Moon Jeong Park a , You Han Bae b , Hong Doo Kim c , Kookheon Char a, * a School of Chemical Engineering and Institute of Chemical Processes, Seoul National University, Seoul 151-744, South Korea b Department of Materials Science and Engineering, K-JIST, Kwang-ju 500-712, South Korea c Department of Chemistry, Kyunghee University, Yongin 449-701, South Korea Received 10 September 2001; received in revised form 4 January 2002; accepted 18 February 2002 Abstract Aqueous solutions of polyethylene oxide-b-dl-lactic acid-co-glycolic acid)-b-ethylene oxide) with two different molecular weights 550±3.4K±550 and 750±3.5K±750) show the change in turbidity as a function of temperature. The variation in turbidity is also found to be independent of block copolymer concentration. By increasing the molecular weight of the hydrophilic PEO end block with the molecular weight of the hydrophobic PLGA middle block kept almost the same, it is found that the phase boundary is shifted to a higher temperature and only soft gels are observed. Large aggregates or clusters of micelles with sizes larger than 5000 nm are observed with dynamic light scattering at the temperatures of turbid region and the size distribution of the aggregates is also found to depend only on temperature, not on concentration. The storage moduli G 0 ) of aqueous solutions of the PEO±PLGA±PEO do not show the abrupt change at the sol-to-hard) gel boundary, as normally seen in the case of PEO±PPO polypropylene oxide))±PEO block copolymers and the behavior of G 0 as a function of temperature is qualitatively the same and independent of polymer concentration except the absolute values of G 0 , which are proportional to the copolymer concentration. This implies that micelle±micelle clusters are formed due to hydrophobic attraction between core phases. q 2002 Elsevier Science Ltd. All rights reserved. Keywords: Polyethylene oxide)±polylactic acid-co-glycolic acid)±polyethylene oxide) PEO±PLGA±PEO) triblock copolymers); Turbidity; Storage modulus G 0 ) 1. Introduction Block copolymers containing both a hydrophilic block such as polyethylene oxide) PEO) and a hydrophobic block such as polypropylene oxide) PPO) or polybutylene oxide) PBO) connected through covalent bonds in a chain generally form micelles [1,2] in a selective solvent when the solution concentration exceeds the critical micelle concen- tration [3±5] or the solution temperature is increased above the critical micelle temperature [3,5,6] due to the self- assembling nature of the amphiphilic chains. Aqueous solu- tions of this kind of amphiphilic block copolymers at high concentrations typically undergo the sol-to-gel transition with increase in temperature. The gels derived from these block copolymers are the physical gels formed through non- covalent associations and those gels can also return to sols when the temperature is lowered below the gelation temperature; in other words, thermoreversible gelation [5,7]. The behavior of the sol-to-gel transition has been utilized for the delivery of labile drugs such as polypeptides and proteins because such hydrophobic drugs can be formu- lated in aqueous solution through a subcutaneous injection to a body [8,9]. Polyethylene oxide-b-propylene oxide-b- ethylene oxide) PEO±PPO±PEO) block copolymer series, typically known as Pluronics w BASF) or Poloxamers w ICI), have extensively been investigated for the drug-deliv- ery system DDS) and their gelation mechanism is relatively well understood by many previous studies [7,10,11]. With increasing the solution temperature and the concentration of the PEO±PPO±PEO for example, PEO-b ±PPO-b ±PEO 4.5K±3.6K±4.5K), Pluronic F127), the average number of unimers per micelle i.e. aggregation number) increases because the unimer±micelle equilibrium is further shifted toward the micellar state [11]. When the aggregation number reaches the plateau value, the micelles eventually come in contact with one another and these contacts cause entanglements among the hydrophilic corona PEO chains [11]. The gel state is thus induced as a result of the micellar packing in close-packed cubic) array [7,10] when the micelle concentration reaches a critical volume fraction of 0.53 [11]. The PEO±PPO±PEO is, however, not biodegradable and its gel phase is found to dissolve in vivo in a short time upon Polymer 43 2002) 3353±3358 0032-3861/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved. PII: S0032-386102)00155-6 www.elsevier.com/locate/polymer * Corresponding author. Tel.: 182-2-880-7431; fax: 182-2-888-7295. E-mail address: khchar@plaza.snu.ac.kr K. Char).