Synthesis and Gelation Properties of PEG−PLA−PEG Triblock Copolymers Obtained by Coupling Monohydroxylated PEG−PLA with Adipoyl Chloride

Abstract

Ring-opening polymerization of D,L-lactide was carried out in the presence of monohydroxylated poly(ethylene glycol) (PEG) with Mn of 2000 and 5000, using zinc powder as catalyst. The resulting PEG-b-polylactide (PEG-PLA) diblocks with various ethylene oxide/lactyl (EO/LA) ratios were coupled with adipoyl chloride to yield PEG-PLA-PEG triblock copolymers. N-Dimethylaminopyridine (DMAP) was used as catalyst. The obtained PEG-PLA-PEG triblock copolymers were characterized by various analytical techniques such as IR, 1H NMR, size exclusion chromatography, X-ray diffraction, and differential scanning calorimetry. Data showed that all the copolymers were semicrystalline with the PEG-type crystalline structure, the crystallinity decreasing with increasing PLA block length. Bioresorbable hydrogels were prepared from the water-soluble triblock copolymers. Rheological measurements showed a gel-sol transition with increasing temperature and gelation was found to be thermoreversible. The copolymer solution behaves like a viscoelastic liquid above the gel point and like a viscoelastic solid below the gel point. The critical gelation concentration, the gel-sol transition temperature at a given concentration, and corresponding moduli depend on both the EO/LA ratio and the molecular weight of the copolymers. It is assumed that gelation results from interactions between PEG blocks at low temperatures and that these interactions are disrupted as the temperature is elevated. The shrinking of PEG blocks with increasing temperature seems to be in agreement with the variation of the gel-sol transition temperatures.

Injectable Biodegradable Hydrogels

“…[10,11] PEG-(D,L-lactide)-PEG (PEG-PLA-PEG) triblock copolymers (MW of MPEG ¼ 2 000-5 000) were recently produced by coupling MPEG-PLA diblock copolymers using adipoyl chloride. [12] Rheological measurements showed a gel-tosol transition in concentrated polymer solutions, with an increase in temperature. Gelation at lower temperatures was attributed to hydrogen bonding between PEG blocks, and the hydrogen bonds were broken at elevated temperatures, leading to the gel-to-sol transition.…”

Thermosensitive Self-Assembling Block Copolymers as Drug Delivery Systems

“…In different articles, Li and co-workers reported the synthesis, characterization, and stereocomplex-induced gelation of PLLA/PEG and PDLA/PEG block copolymers. The copolymers were synthesized by ring-opening polymerization of L-or D-lactide in the presence of mono-or dihydroxylated PEG, using zinc metal as catalyst [71,72].…”

“…N-Dimethylaminopyridine (DMAP) was used as catalyst. This reaction led to formation of an ester bond between PLA and PEG blocks ( Figure 3) [71]. Zhang et al synthesized PLA-PEG-PLA copolymers by ring opening polymerization of L-or d-lactide in the presence of dihydroxyl PEG using zinc lactate as catalyst.…”

“…In fact both dynamic mechanical and flow curve analyses were used to identify sol-to-gel transitions at increasing temperature [65,71,78].…”

“…Then 1 H NMR and 13 C NMR analysis were used to study composition and microenvironment change during sol-to-gel transition and structure and composition of the synthesized triblock copolymers [63,65,67,71,78]. As an example, Zhang et al used 1H NMR and differential scanning calorimetry (DSC) analysis to characterize the synthesized PLLA-PEG-PLLA and PDLA-PEG-PDLA block copolymers.…”