Thermogelling water solutions of multifunctional macromonomers based on PLGA-PEG-PLGA triblock copolymers

Biodegradable thermosensitive triblock copolymers based on poly(ethylene glycol) and poly[(lactic acid)-co-(glycolic acid)](PLGA-PEG-PLGA) with PLGA/PEG weight ratio in the range of 1.5–3.0 and LA/GA molar ratio equal to 2.4 or 3.0 were prepared via ring opening polymerization (ROP). Prepared copolymers were subsequently modified in “one pot” by itaconic anhydride (ITA) in order to functionalize both ends with carboxylic acid groups and reactive double bonds. Chemical structure was characterized by means of gel permeation chromatography and nuclear magnetic resonance. Aqueous solutions of both modified and unmodified copolymers are able to form free flowing sol at room temperature and clear gel at temperature around 37°C. Therefore, sol-gel transitions of PLGA-PEG-PLGA and ITA/PLGA-PEG-PLGA/ITA copolymers in aqueous solutions were investigated using test tube inverting method. No mater if copolymer is modified or not, it was found that the critical gel temperature (CGT) increased when the PLGA/PEG weight ratio dropped from 2.5 to 2.0 and that the critical gel concentration (CGC) grew up with decreasing molar ratio of LA/GA from 3.0 up to 2.4. However, in all cases the ITA functionalization improved sol-gel characteristics of original PLGA-PEG-PLGA copolymer by approaching gel phase to body temperature. As a result, aqueous solution of ITA/PLGA-PEG-PLGA/ITA having LA/GA = 3 and PLGA/PEG = 2 with concentration higher than 6 wt% might be suitable material for biomedical applications as injectable temporary implants.