The Effect of PLGA-PEG-PLGA Modification on the Sol-gel Transition and Degradation Properties

Abstract

This paper deals with the influence of an incubation medium pH on the hydrolytic degradation of a novel thermosensitive biodegradable triblock copolymer based on hydrophilic poly(ethylene glycol) and hydrophobic copolymer poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA), consequently modified at alpha,omega-ends with itaconic acid (ITA) resulting in alpha,omega-itaconyl(PLGA-PEG-PLGA). Itaconic acid, gained from renewable resources, delivers a reactive double bond and carboxylic functional group to the end of PLGA-PEG-PLGA copolymer: this is important for a reaction with biologically active substances. The suitability of the sample degradation was assessed depending on whether the copolymer formed a gel at 37 °C. Two reversible physical sol-gel-sol transitions from a sol (liquid phase) to a gel (solid phase) and back to a sol (suspension) were verified using the tube inverting method. The hydrolytical degradation was evaluated at a physiological temperature (37 °C) in the presence of phosphate solutions, at a pH either 4.2 or 7.4 by monitoring the decrease of the number average molecular weight of copolymers by GPC. Moreover, the degradation kinetics was confirmed by the HPLC/DAD method, where the increasing amount of final degradation products (lactic and glycolic acids) was detected. The study demonstrated that the carboxylic groups modified copolymer is more susceptible to hydrolytical degradation than the unmodified copolymer within first days of degradation at 7.4.

This paper deals with the influence of an incubation medium pH on the hydrolytic degradation of a novel thermosensitive biodegradable triblock copolymer based on hydrophilic poly(ethylene glycol) and hydrophobic copolymer poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA), consequently modified at alpha,omega-ends with itaconic acid (ITA) resulting in alpha,omega-itaconyl(PLGA-PEG-PLGA). Itaconic acid, gained from renewable resources, delivers a reactive double bond and carboxylic functional group to the end of PLGA-PEG-PLGA copolymer: this is important for a reaction with biologically active substances. The suitability of the sample degradation was assessed depending on whether the copolymer formed a gel at 37 °C. Two reversible physical sol-gel-sol transitions from a sol (liquid phase) to a gel (solid phase) and back to a sol (suspension) were verified using the tube inverting method. The hydrolytical degradation was evaluated at a physiological temperature (37 °C) in the presence of phosphate solutions, at a pH either 4.2 or 7.4 by monitoring the decrease of the number average molecular weight of copolymers by GPC. Moreover, the degradation kinetics was confirmed by the HPLC/DAD method, where the increasing amount of final degradation products (lactic and glycolic acids) was detected. The study demonstrated that the carboxylic groups modified copolymer is more susceptible to hydrolytical degradation than the unmodified copolymer within first days of degradation at 7.4.