Novel thymopentin release systems prepared from bioresorbable PLA–PEG–PLA hydrogels

Abstract

Copolymers were synthesized by ring opening polymerization of l- or d-lactide in the presence of dihydroxyl PEG with molar mass of 6000, 12,000 and 20,000, using zinc lactate as catalyst. Bioresorbable hydrogels were obtained by mixing PLLA–PEG–PLLA and PDLA–PEG–PDLA aqueous solutions due to stereocomplexation between PLLA and PDLA chains. Rheological measurements show that the hydrogels present typical viscoelastic behaviors, although degradation could occur during the gelation process. Thymopentin was taken as a model drug to evaluate the potential of PLA–PEG–PLA hydrogels as carrier of hydrophilic drugs. Various parameters such as copolymer concentration, drug load, copolymer composition and the difference between sol and gel were considered. The release profiles are characterized by an initial burst followed by slower release. Higher copolymer concentration leads to slower release rate and less burst effect due to more compact structure which disfavors drug diffusion. Similarly, higher molar mass of the copolymers disfavors the release of TP5, and hydrogels composed of both PLLA/PEG and PDLA/PEG present slower release rates than single copolymer solutions. In contrast, drug load exhibits little influence on the release profiles due to the high water solubility of TP5. In all cases, nearly 80% of TP5 is released. In vivo studies proved the potential of TP5 containing hydrogels, especially those with a concentration of 25%. Both the CD4 +/CD8 + ratio and the morphology of thymus indicate the immunization efficacy of the TP5 release systems based on PLA/PEG hydrogels.